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Pico OA, Espinoza F, Cádiz MI, Sossa CL, Becerra-Bayona SM, Salgado MCC, Rodríguez JER, Cárdenas OFV, Cure JMQ, Khoury M, Arango-Rodríguez ML. Efficacy of a single dose of cryopreserved human umbilical cord mesenchymal stromal cells for the treatment of knee osteoarthritis:a randomized, controlled, double-blind pilot study. Cytotherapy 2025; 27:188-200. [PMID: 39503681 DOI: 10.1016/j.jcyt.2024.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 09/14/2024] [Accepted: 09/25/2024] [Indexed: 11/08/2024]
Abstract
BACKGROUND Knee osteoarthritis (OA) is the most prevalent degenerative musculoskeletal disorder, which is particularly common in older population. While conventional treatments have limited effectiveness, the development of more effective therapeutic strategies is necessary to address this primary source of pain and disability. Umbilical cord mesenchymal stromal cells (UC-MSCs) offer a promising therapeutic approach for treating knee OA. AIM This randomized, prospective, double-blind and controlled pilot study was carried out to evaluate and compare the safety and therapeutic efficacy of a single intra-articular injection of a standardized product CellistemOA (5 × 106 ± 5 × 105 UC-MSCs), vs. triamcinolone (a synthetic corticosteroid) (10 mg/mL) in thirty patients with symptomatic knee OA (Kellgren-Lawrence grade II or III). METHODS The outcomes included changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores based on a Likert scale, numerical rating score (NRS) for pain, Magnetic Resonance Imaging (MRI), and quality of life (SF-36 questionnaire), from baseline and throughout 12-months of follow-up. RESULTS Patients treated with CellistemOA showed significant improvement in WOMAC score (including the three subscale scores (pain, stiffness and function), NRS in pain, and SF-36 profile from baseline to 12 months (p < 0.05) compared to the triamcinolone group, and no severe adverse events were reported. There were no significant differences in MRI WORMS scores between the two groups. However, patients who received the cellular treatment experienced a significant improvement in their SF-36 profile (p < 0.05). CONCLUSIONS This pilot study revealed that a single dose of CellistemOA is safe and superior to the active comparator in knee OA at 1-year of follow-up, making it a compelling therapeutic alternative to treat symptomatic OA patients.
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Affiliation(s)
- Omar Amado Pico
- Fundación Oftalmológica de Santander - FOSCAL, Floridablanca, Colombia; Facultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga - UNAB, Bucaramanga, Colombia
| | - Francisco Espinoza
- Cells for Cells & Consorcio Regenero, Santiago, Chile; Program for Translational Research in Cell Therapy, Universidad de los Andes, Santiago, Chile; Department of Rheumatology, Universidad de los Andes, Santiago, Chile; IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile
| | - María Ignacia Cádiz
- Cells for Cells & Consorcio Regenero, Santiago, Chile; IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile; Laboratory of Nano-Regenerative Medicine, Universidad de los Andes, Santiago, Chile
| | - Claudia L Sossa
- Facultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga - UNAB, Bucaramanga, Colombia; Programa para el Tratamiento y Estudio de Enfermedades Hematológicas y Oncológicas de Santander (PROTEHOS), Floridablanca, Colombia
| | - Silvia M Becerra-Bayona
- Facultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga - UNAB, Bucaramanga, Colombia
| | - María C Canencio Salgado
- Facultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga - UNAB, Bucaramanga, Colombia
| | | | | | | | - Maroun Khoury
- Cells for Cells & Consorcio Regenero, Santiago, Chile; Program for Translational Research in Cell Therapy, Universidad de los Andes, Santiago, Chile; IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile; Laboratory of Nano-Regenerative Medicine, Universidad de los Andes, Santiago, Chile
| | - Martha L Arango-Rodríguez
- Facultad de Ciencias de la Salud, Universidad Autónoma de Bucaramanga - UNAB, Bucaramanga, Colombia; Banco Multitejidos y Centro de Terapias Avanzadas, Clínica FOSCAL Internacional, Floridablanca, Colombia.
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de Sousa Moreira A, Lopes B, Sousa AC, Coelho A, Sousa P, Araújo A, Delgado E, Alvites R, Maurício AC. Stem Cell-Based Therapies for Glaucoma Treatment: A Review Bridging the Gap in Veterinary Patients. Int J Mol Sci 2024; 26:232. [PMID: 39796087 PMCID: PMC11719664 DOI: 10.3390/ijms26010232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 12/24/2024] [Accepted: 12/27/2024] [Indexed: 01/13/2025] Open
Abstract
Retinal diseases are characterized by progressive damage to retinal cells, leading to irreversible vision loss. Among these, glaucoma stands out as a multifactorial neurodegenerative disease involving elevated intraocular pressure, retinal ganglion cell apoptosis, and optic nerve damage, ultimately resulting in blindness in both humans and dogs. Stem cell-based therapies have emerged as a promising therapeutic option for such conditions due to their regenerative and neuroprotective potential. These therapies, particularly those based on mesenchymal stem cells, offer the potential to repair and protect retinal tissues through the bioactive molecules (growth factors, cytokines, chemokines) secreted, their secretome. However, research in this field, especially on the use of umbilical cord mesenchymal stem cells' secretome, remains sparse. Most clinical trials focus on human glaucomatous patients, leaving a significant gap in veterinary patients' application, especially in dogs, with additional research being needed to determine its usefulness in canine glaucoma treatment. Future studies should aim to evaluate these therapies across both human and veterinary contexts, broadening treatment possibilities for glaucoma.
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Affiliation(s)
- Alícia de Sousa Moreira
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA) da Universidade do Porto (UP), Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal; (A.d.S.M.); (B.L.); (A.C.S.); (A.C.); (P.S.); (R.A.)
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal;
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Faculdade de Medicina Veterinária (FMV), Universidade de Lisboa (UL), Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal;
| | - Bruna Lopes
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA) da Universidade do Porto (UP), Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal; (A.d.S.M.); (B.L.); (A.C.S.); (A.C.); (P.S.); (R.A.)
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal;
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Faculdade de Medicina Veterinária (FMV), Universidade de Lisboa (UL), Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal;
| | - Ana Catarina Sousa
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA) da Universidade do Porto (UP), Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal; (A.d.S.M.); (B.L.); (A.C.S.); (A.C.); (P.S.); (R.A.)
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal;
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Faculdade de Medicina Veterinária (FMV), Universidade de Lisboa (UL), Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal;
| | - André Coelho
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA) da Universidade do Porto (UP), Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal; (A.d.S.M.); (B.L.); (A.C.S.); (A.C.); (P.S.); (R.A.)
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal;
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Faculdade de Medicina Veterinária (FMV), Universidade de Lisboa (UL), Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal;
| | - Patrícia Sousa
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA) da Universidade do Porto (UP), Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal; (A.d.S.M.); (B.L.); (A.C.S.); (A.C.); (P.S.); (R.A.)
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal;
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Faculdade de Medicina Veterinária (FMV), Universidade de Lisboa (UL), Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal;
| | - Ana Araújo
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal;
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Faculdade de Medicina Veterinária (FMV), Universidade de Lisboa (UL), Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal;
| | - Esmeralda Delgado
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Faculdade de Medicina Veterinária (FMV), Universidade de Lisboa (UL), Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal;
- Centro de Investigação Interdisciplinar em Sanidade Animal (CIISA), Faculdade de Medicina Veterinária (FMV), Universidade de Lisboa (UL), Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal
| | - Rui Alvites
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA) da Universidade do Porto (UP), Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal; (A.d.S.M.); (B.L.); (A.C.S.); (A.C.); (P.S.); (R.A.)
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal;
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Faculdade de Medicina Veterinária (FMV), Universidade de Lisboa (UL), Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal;
- Instituto Universitário de Ciências da Saúde (CESPU), Avenida Central de Gandra n° 1317, 4585-116 Paredes, Portugal
| | - Ana Colette Maurício
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente (ICETA) da Universidade do Porto (UP), Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal; (A.d.S.M.); (B.L.); (A.C.S.); (A.C.); (P.S.); (R.A.)
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal;
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), Faculdade de Medicina Veterinária (FMV), Universidade de Lisboa (UL), Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal;
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Shen J, Ye D, Jin H, Wu Y, Peng L, Liang Y. Porcine nasal septum cartilage-derived decellularized matrix promotes chondrogenic differentiation of human umbilical mesenchymal stem cells without exogenous growth factors. J Mater Chem B 2024; 12:5513-5524. [PMID: 38745541 DOI: 10.1039/d3tb03077f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2024]
Abstract
BACKGROUND In the domain of plastic surgery, nasal cartilage regeneration is of significant importance. The extracellular matrix (ECM) from porcine nasal septum cartilage has shown potential for promoting human cartilage regeneration. Nonetheless, the specific biological inductive factors and their pathways in cartilage tissue engineering remain undefined. METHODS The decellularized matrix derived from porcine nasal septum cartilage (PN-DCM) was prepared using a grinding method. Human umbilical cord mesenchymal stem cells (HuMSCs) were cultured on these PN-DCM scaffolds for 4 weeks without exogenous growth factors to evaluate their chondroinductive potential. Subsequently, proteomic analysis was employed to identify potential biological inductive factors within the PN-DCM scaffolds. RESULTS Compared to the TGF-β3-cultured pellet model serving as a positive control, the PN-DCM scaffolds promoted significant deposition of a Safranin-O positive matrix and Type II collagen by HuMSCs. Gene expression profiling revealed upregulation of ACAN, COL2A1, and SOX9. Proteomic analysis identified potential chondroinductive factors in the PN-DCM scaffolds, including CYTL1, CTGF, MGP, ITGB1, BMP7, and GDF5, which influence HuMSC differentiation. CONCLUSION Our findings have demonstrated that the PN-DCM scaffolds promoted HuMSC differentiation towards a nasal chondrocyte phenotype without the supplementation of exogenous growth factors. This outcome is associated with the chondroinductive factors present within the PN-DCM scaffolds.
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Affiliation(s)
- Jinpeng Shen
- Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Guizhou, P. R. China.
- Department of Plastic Surgery and Burn Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, P. R. China.
- Department of Plastic Surgery, Taizhou Enze Medical Center, Zhejiang, P. R. China
| | - Danyan Ye
- Research Center for Translational Medicine, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, P. R. China
| | - Hao Jin
- Department of Cardiology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, P. R. China
| | - Yongxuan Wu
- Department of Plastic Surgery and Burn Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, P. R. China.
| | - Lihong Peng
- Department of Plastic Surgery and Burn Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, P. R. China.
| | - Yan Liang
- Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Guizhou, P. R. China.
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Nadeem G, Theerakittayakorn K, Somredngan S, Thi Nguyen H, Boonthai T, Samruan W, Tangkanjanavelukul P, Parnpai R. Induction of Human Wharton's Jelly of Umbilical Cord Derived Mesenchymal Stem Cells to Be Chondrocytes and Transplantation in Guinea Pig Model with Spontaneous Osteoarthritis. Int J Mol Sci 2024; 25:5673. [PMID: 38891860 PMCID: PMC11171648 DOI: 10.3390/ijms25115673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 05/16/2024] [Accepted: 05/17/2024] [Indexed: 06/21/2024] Open
Abstract
Osteoarthritis (OA) is a degenerative joint disease commonly found in elderly people and obese patients. Currently, OA treatments are determined based on their condition severity and a medical professional's advice. The aim of this study was to differentiate human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) into chondrocytes for transplantation in OA-suffering guinea pigs. hWJ-MSCs were isolated using the explant culture method, and then, their proliferation, phenotypes, and differentiation ability were evaluated. Subsequently, hWJ-MSCs-derived chondrocytes were induced and characterized based on immunofluorescent staining, qPCR, and immunoblotting techniques. Then, early-OA-suffering guinea pigs were injected with hyaluronic acid (HA) containing either MSCs or 14-day-old hWJ-MSCs-derived chondrocytes. Results showed that hWJ-MSCs-derived chondrocytes expressed specific markers of chondrocytes including Aggrecan, type II collagen, and type X collagen proteins and β-catenin, Sox9, Runx2, Col2a1, Col10a1, and ACAN gene expression markers. Administration of HA plus hWJ-MSCs-derived chondrocytes (HA-CHON) produced a better recovery rate of degenerative cartilages than HA plus MSCs or only HA. Histological assessments demonstrated no significant difference in Mankin's scores of recovered cartilages between HA-CHON-treated guinea pigs and normal articular cartilage guinea pigs. Transplantation of hWJ-MSCs-derived chondrocytes was more effective than undifferentiated hWJ-MSCs or hyaluronic acid for OA treatment in guinea pigs. This study provides a promising treatment to be used in early OA patients to promote recovery and prevent disease progression to severe osteoarthritis.
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Affiliation(s)
- Gulrez Nadeem
- Embryo Technology and Stem Cell Research Center, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand; (G.N.); (K.T.); (S.S.); (H.T.N.); (T.B.); (W.S.)
| | - Kasem Theerakittayakorn
- Embryo Technology and Stem Cell Research Center, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand; (G.N.); (K.T.); (S.S.); (H.T.N.); (T.B.); (W.S.)
| | - Sirilak Somredngan
- Embryo Technology and Stem Cell Research Center, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand; (G.N.); (K.T.); (S.S.); (H.T.N.); (T.B.); (W.S.)
| | - Hong Thi Nguyen
- Embryo Technology and Stem Cell Research Center, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand; (G.N.); (K.T.); (S.S.); (H.T.N.); (T.B.); (W.S.)
| | - Traimat Boonthai
- Embryo Technology and Stem Cell Research Center, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand; (G.N.); (K.T.); (S.S.); (H.T.N.); (T.B.); (W.S.)
| | - Worawalan Samruan
- Embryo Technology and Stem Cell Research Center, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand; (G.N.); (K.T.); (S.S.); (H.T.N.); (T.B.); (W.S.)
| | - Ponthep Tangkanjanavelukul
- School of Orthopedic Surgery, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand
| | - Rangsun Parnpai
- Embryo Technology and Stem Cell Research Center, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand; (G.N.); (K.T.); (S.S.); (H.T.N.); (T.B.); (W.S.)
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Yuan HL, Chang L, Fan WW, Liu X, Li Q, Tian C, Zhao J, Li ZA, Pan XH, Zhu XQ. Application and challenges of stem cells in cardiovascular aging. Regen Ther 2024; 25:1-9. [PMID: 38108044 PMCID: PMC10724492 DOI: 10.1016/j.reth.2023.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 10/17/2023] [Accepted: 11/16/2023] [Indexed: 12/19/2023] Open
Abstract
With the rapid development of society and the economy, population aging has become a common challenge faced by many countries in the world today. Structural and functional changes in the cardiovascular system can occur with age, increasing the incidence and severity of cardiovascular diseases in older adults. Due to the limited regenerative capacity of myocardial cells, myocardial infarction and its resulting heart failure and congenital heart disease have become the number one killer of human health. At present, the treatment of cardiovascular diseases includes drug therapy and nondrug therapy. Nondrug therapy mainly includes minimally invasive interventional therapy, surgical diagnosis and treatment, and cell therapy. Long-term drug treatment may cause headache due to vasodilation, lower blood pressure, digestive system dysfunction and other side effects. Surgical treatment is traumatic, difficult to treat, and expensive. In recent years, stem cell therapy has exhibited broad application prospects in basic and clinical research on cardiovascular disease because of its plasticity, self-renewal and multidirectional differentiation potential. Therefore, this paper looks at stem cell therapy for diseases, reviews recent advances in the mechanism and clinical transformation of cardiovascular aging and related diseases in China, and briefly discusses the development trend and future prospects of cardiovascular aging research.
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Affiliation(s)
- He-Ling Yuan
- The Basic Medical Laboratory of the 920th Hospital of Joint Logistics Support Force of PLA, The Transfer Medicine Key Laboratory of Cell Therapy Technology of Yunan Province, The Integrated Engineering Laboratory of Cell Biological Medicine of State and Regions, Kunming 650032, Yunnan Province, China
- Kunming Medical University, Kunming, Yunnan 650500, China
| | - Le Chang
- The Basic Medical Laboratory of the 920th Hospital of Joint Logistics Support Force of PLA, The Transfer Medicine Key Laboratory of Cell Therapy Technology of Yunan Province, The Integrated Engineering Laboratory of Cell Biological Medicine of State and Regions, Kunming 650032, Yunnan Province, China
| | - Wei-Wen Fan
- The Basic Medical Laboratory of the 920th Hospital of Joint Logistics Support Force of PLA, The Transfer Medicine Key Laboratory of Cell Therapy Technology of Yunan Province, The Integrated Engineering Laboratory of Cell Biological Medicine of State and Regions, Kunming 650032, Yunnan Province, China
- Kunming Medical University, Kunming, Yunnan 650500, China
| | - Xin Liu
- The Basic Medical Laboratory of the 920th Hospital of Joint Logistics Support Force of PLA, The Transfer Medicine Key Laboratory of Cell Therapy Technology of Yunan Province, The Integrated Engineering Laboratory of Cell Biological Medicine of State and Regions, Kunming 650032, Yunnan Province, China
- Kunming Medical University, Kunming, Yunnan 650500, China
| | - Qiang Li
- The Basic Medical Laboratory of the 920th Hospital of Joint Logistics Support Force of PLA, The Transfer Medicine Key Laboratory of Cell Therapy Technology of Yunan Province, The Integrated Engineering Laboratory of Cell Biological Medicine of State and Regions, Kunming 650032, Yunnan Province, China
- Kunming Medical University, Kunming, Yunnan 650500, China
| | - Chuan Tian
- The Basic Medical Laboratory of the 920th Hospital of Joint Logistics Support Force of PLA, The Transfer Medicine Key Laboratory of Cell Therapy Technology of Yunan Province, The Integrated Engineering Laboratory of Cell Biological Medicine of State and Regions, Kunming 650032, Yunnan Province, China
| | - Jing Zhao
- The Basic Medical Laboratory of the 920th Hospital of Joint Logistics Support Force of PLA, The Transfer Medicine Key Laboratory of Cell Therapy Technology of Yunan Province, The Integrated Engineering Laboratory of Cell Biological Medicine of State and Regions, Kunming 650032, Yunnan Province, China
| | - Zi-An Li
- The Basic Medical Laboratory of the 920th Hospital of Joint Logistics Support Force of PLA, The Transfer Medicine Key Laboratory of Cell Therapy Technology of Yunan Province, The Integrated Engineering Laboratory of Cell Biological Medicine of State and Regions, Kunming 650032, Yunnan Province, China
| | - Xing-Hua Pan
- The Basic Medical Laboratory of the 920th Hospital of Joint Logistics Support Force of PLA, The Transfer Medicine Key Laboratory of Cell Therapy Technology of Yunan Province, The Integrated Engineering Laboratory of Cell Biological Medicine of State and Regions, Kunming 650032, Yunnan Province, China
| | - Xiang-Qing Zhu
- The Basic Medical Laboratory of the 920th Hospital of Joint Logistics Support Force of PLA, The Transfer Medicine Key Laboratory of Cell Therapy Technology of Yunan Province, The Integrated Engineering Laboratory of Cell Biological Medicine of State and Regions, Kunming 650032, Yunnan Province, China
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Seyyedin S, Ezzatabadipour M, Nematollahi-Mahani SN. The Role of Various Factors in Neural Differentiation of Human Umbilical Cord Mesenchymal Stem Cells with a Special Focus on the Physical Stimulants. Curr Stem Cell Res Ther 2024; 19:166-177. [PMID: 36734908 DOI: 10.2174/1574888x18666230124151311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Revised: 10/05/2022] [Accepted: 11/25/2022] [Indexed: 02/04/2023]
Abstract
Human umbilical cord matrix-derived mesenchymal stem cells (hUCMs) are considered as ideal tools for cell therapy procedures and regenerative medicine. The capacity of these cells to differentiate into neural lineage cells make them potentially important in the treatment of various neurodegenerative diseases. An electronic search was performed in Web of Science, PubMed/MEDLINE, Scopus and Google Scholar databases for articles published from January 1990 to March 2022. This review discusses the current knowledge on the effect of various factors, including physical, chemical and biological stimuli which play a key role in the differentiation of hUCMs into neural and glial cells. Moreover, the currently understood molecular mechanisms involved in the neural differentiation of hUCMs under various environmental stimuli are reviewed. Various stimuli, especially physical stimuli and specifically different light sources, have revealed effects on neural differentiation of mesenchymal stem cells, including hUCMs; however, due to the lack of information about the exact mechanisms, there is still a need to find optimal conditions to promote the differentiation capacity of these cells which in turn can lead to significant progress in the clinical application of hUCMs for the treatment of neurological disorders.
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Affiliation(s)
- Sajad Seyyedin
- Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Massood Ezzatabadipour
- Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
- Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Seyed Noureddin Nematollahi-Mahani
- Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
- Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran
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Motallebzadeh Khanmiri J, Mousavi SH, Alizadeh S, Khani-Eshratabadi M. Microvesicles Derived from Human Placental Mesenchymal Stem Cells Induce Autophagy and Apoptosis in Acute Myeloid Leukemia. JOURNAL OF ADVANCES IN MEDICAL AND BIOMEDICAL RESEARCH 2023; 31:574-584. [DOI: 10.30699/jambs.31.149.574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/08/2025]
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Prakash N, Kim J, Jeon J, Kim S, Arai Y, Bello AB, Park H, Lee SH. Progress and emerging techniques for biomaterial-based derivation of mesenchymal stem cells (MSCs) from pluripotent stem cells (PSCs). Biomater Res 2023; 27:31. [PMID: 37072836 PMCID: PMC10114339 DOI: 10.1186/s40824-023-00371-0] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 03/26/2023] [Indexed: 04/20/2023] Open
Abstract
The use of mesenchymal stem cells (MSCs) for clinical purposes has skyrocketed in the past decade. Their multilineage differentiation potentials and immunomodulatory properties have facilitated the discovery of therapies for various illnesses. MSCs can be isolated from infant and adult tissue sources, which means they are easily available. However, this raises concerns because of the heterogeneity among the various MSC sources, which limits their effective use. Variabilities arise from donor- and tissue-specific differences, such as age, sex, and tissue source. Moreover, adult-sourced MSCs have limited proliferation potentials, which hinders their long-term therapeutic efficacy. These limitations of adult MSCs have prompted researchers to develop a new method for generating MSCs. Pluripotent stem cells (PSCs), such as embryonic stem cells and induced PSCs (iPSCs), can differentiate into various types of cells. Herein, a thorough review of the characteristics, functions, and clinical importance of MSCs is presented. The existing sources of MSCs, including adult- and infant-based sources, are compared. The most recent techniques for deriving MSCs from iPSCs, with a focus on biomaterial-assisted methods in both two- and three-dimensional culture systems, are listed and elaborated. Finally, several opportunities to develop improved methods for efficiently producing MSCs with the aim of advancing their various clinical applications are described.
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Affiliation(s)
- Nityanand Prakash
- Department of Biomedical Engineering, Dongguk University, Seoul, 04620, Korea
| | - Jiseong Kim
- Department of Biomedical Engineering, Dongguk University, Seoul, 04620, Korea
| | - Jieun Jeon
- Department of Biomedical Engineering, Dongguk University, Seoul, 04620, Korea
| | - Siyeon Kim
- Department of Biomedical Engineering, Dongguk University, Seoul, 04620, Korea
| | - Yoshie Arai
- Department of Biomedical Engineering, Dongguk University, Seoul, 04620, Korea
| | - Alvin Bacero Bello
- Department of Biomedical Engineering, Dongguk University, Seoul, 04620, Korea.
| | - Hansoo Park
- School of Integrative Engineering, Chung-Ang University, Seoul, 06911, Korea.
| | - Soo-Hong Lee
- Department of Biomedical Engineering, Dongguk University, Seoul, 04620, Korea.
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9
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Song JS, Hong KT, Kim NM, Hwangbo BH, Yang BS, Victoroff BN, Choi NH. Clinical and Magnetic Resonance Imaging Outcomes After Human Cord Blood-Derived Mesenchymal Stem Cell Implantation for Chondral Defects of the Knee. Orthop J Sports Med 2023; 11:23259671231158391. [PMID: 37123990 PMCID: PMC10134134 DOI: 10.1177/23259671231158391] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 01/17/2023] [Indexed: 05/02/2023] Open
Abstract
Background There is a paucity of literature reporting clinical and magnetic resonance imaging (MRI) outcomes after allogeneic umbilical cord blood-derived mesenchymal stem cell (UCB-MSC) implantation for chondral defects of the knee. Purpose To report clinical and MRI outcomes after UCB-MSC implantation for chondral lesions of the knee. Study Design Case series; Level of evidence, 4. Methods Inclusion criteria were patients aged between 40 and 70 years with focal chondral lesions of grade 3 or 4 on the medial femoral condyle, defect sizes >4 cm2, and intact ligaments. Exclusion criteria were patients who required realignment osteotomy or who had a meniscal deficiency, ligamentous instability, or a concomitant full-thickness chondral defect in the lateral or patellofemoral compartment. A mixture of human UCB-MSCs and sodium hyaluronate was implanted into the chondral defect through mini-arthrotomy. MRI at 1-year follow-up was performed to evaluate repaired cartilage hypertrophy. Repaired cartilage thickness was measured, and hypertrophy was classified as grade 1 (<125%), grade 2 (<150%), or grade 3 (<200%). Patient-reported outcomes (PROs; International Knee Documentation Committee, visual analog scale for pain, and Western Ontario and McMaster Universities Osteoarthritis Index) were evaluated preoperatively and at 1, 2, and 3 years postoperatively. Repaired cartilage hypertrophy was evaluated for a correlation with PRO scores. Results Enrolled were 85 patients with a mean age of 56.8 ± 6.1 years and a mean chondral defect size of 6.7 ± 2.0 cm2. At follow-up, a significant improvement in all PRO scores was seen compared with preoperatively (P < .001 for all). MRI at 1-year follow-up demonstrated that 28 patients had grade 1 repaired cartilage hypertrophy, 41 patients had grade 2, and 16 patients had grade 3. MRI performed in 11 patients at 2 years after surgery indicated no difference in repaired cartilage hypertrophy between the 1- and 2-year time points. The grade of repaired cartilage hypertrophy did not correlate with PRO scores. Conclusion Clinical outcomes improved significantly at short-term follow-up after UCB-MSC implantation. Although all patients showed repaired cartilage hypertrophy, it did not correlate with clinical outcomes.
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Affiliation(s)
- Jun-Seob Song
- Department of Orthopedic Surgery, Gangnam JS Hospital, Seoul, Republic of Korea
| | - Ki-Taek Hong
- Department of Orthopedic Surgery, Gangnam JS Hospital, Seoul, Republic of Korea
| | - Na-Min Kim
- Department of Orthopedic Surgery, Gangnam JS Hospital, Seoul, Republic of Korea
| | - Byung-Hun Hwangbo
- Department of Orthopedic Surgery, Nowon Eulji Medical Center, Eulji University, Seoul, Republic of Korea
| | - Bong-Seok Yang
- Department of Orthopedic Surgery, Shihwa Medical Center, Siheung, Republic of Korea
| | - Brian N. Victoroff
- Department of Orthopaedic Surgery, Case Western Reserve University, Cleveland, Ohio, USA
| | - Nam-Hong Choi
- Department of Orthopedic Surgery, Nowon Eulji Medical Center, Eulji University, Seoul, Republic of Korea
- Nam-Hong Choi, MD, Department of Orthopedic Surgery, Nowon Eulji Medical Center, Eulji University, 280-1, Hagye-1-dong, Nowon-gu, Seoul, 139-711, Republic of Korea ()
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10
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Umbilical Cord Mesenchymal Stromal Cells for Cartilage Regeneration Applications. Stem Cells Int 2022; 2022:2454168. [PMID: 35035489 PMCID: PMC8758292 DOI: 10.1155/2022/2454168] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 10/13/2021] [Accepted: 11/23/2021] [Indexed: 11/30/2022] Open
Abstract
Chondropathies are increasing worldwide, but effective treatments are currently lacking. Mesenchymal stromal cell (MSCs) transplantation represents a promising approach to counteract the degenerative and inflammatory environment characterizing those pathologies, such as osteoarthritis (OA) and rheumatoid arthritis (RA). Umbilical cord- (UC-) MSCs gained increasing interest due to their multilineage differentiation potential, immunomodulatory, and anti-inflammatory properties as well as higher proliferation rates, abundant supply along with no risks for the donor compared to adult MSCs. In addition, UC-MSCs are physiologically adapted to survive in an ischemic and nutrient-poor environment as well as to produce an extracellular matrix (ECM) similar to that of the cartilage. All these characteristics make UC-MSCs a pivotal source for a stem cell-based treatment of chondropathies. In this review, the regenerative potential of UC-MSCs for the treatment of cartilage diseases will be discussed focusing on in vitro, in vivo, and clinical studies.
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11
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Said YM, El-Gamel NEA, Ali SA, Mohamed AF. Evaluation of Human Wharton's Jelly-Derived Mesenchymal Stem Cells Conditioning Medium (hWJ-MSCs-CM) or Scorpion Venom Breast Cancer Cell Line In Vitro. J Gastrointest Cancer 2022; 53:888-901. [PMID: 34988906 DOI: 10.1007/s12029-021-00762-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/12/2021] [Indexed: 10/19/2022]
Abstract
PURPOSE The present study aimed to evaluate the anticancer potential of Egyptian scorpion Leiurus quinquestriatus venom (ScV) or human Wharton's jelly-derived mesenchymal stem cells conditioning medium (hWJ-MSCs-CM)/CM against breast cancer (MCF-7) cell line as an alternative effective cancer biotherapy. METHODS Venom (ScV) toxicity was performed recording concentration-dependent viability % and ScV IC50 value was in the order of 100 μg/ml. MCF-7 were treated with hWJ-MSCs-CM used as (25%, 50%, and 75% ml) or the IC50 of ScV. Apoptotic activity was traced via evaluation the apoptotic (Bax, Casp-3, and Casp-9) and anti-apoptotic genes (Bcl2, ALDOA, and PKM2) profile. RESULTS Both Bax and Casp-3 showed a significant upregulation while anti-apoptotic genes were significantly downregulated. In the meantime, Casp-3 and Casp-9 protein were monitored using ELISA, and their level was less than in control. Additionally, MCF-7 apoptosis was monitored using flow cytometry recording a significant DNA accumulation in the G0-G1 and S phases in case of cell treatment with ScV or CM75% ml and 50% ml. Also, there was a significant total necrotic cells % compared with control cells, and total apoptosis under the effect of ScV or CM75% ml was significantly elevated than rest of treatment. CONCLUSION Apoptosis induction was both dose- and time-dependent for hWJ-MSCs-CM and ScV. According to the present study and other studies, there is an ample evidence that hWJ-MSCs-CM and the venom IC50 abolish tumor growth.
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Affiliation(s)
| | - Nadia E A El-Gamel
- Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt.
| | - Said A Ali
- Department of Biophysics, Faculty of Science, Cairo University, Giza, Egypt
| | - Aly Fahmy Mohamed
- The International Center for Advanced Researches (ICTAR), Giza, Egypt
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12
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Battafarano G, Rossi M, De Martino V, Marampon F, Borro L, Secinaro A, Del Fattore A. Strategies for Bone Regeneration: From Graft to Tissue Engineering. Int J Mol Sci 2021; 22:ijms22031128. [PMID: 33498786 PMCID: PMC7865467 DOI: 10.3390/ijms22031128] [Citation(s) in RCA: 117] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 01/08/2021] [Accepted: 01/20/2021] [Indexed: 12/12/2022] Open
Abstract
Bone is a regenerative organ characterized by self-renewal ability. Indeed, it is a very dynamic tissue subjected to continuous remodeling in order to preserve its structure and function. However, in clinical practice, impaired bone healing can be observed in patients and medical intervention is needed to regenerate the tissue via the use of natural bone grafts or synthetic bone grafts. The main elements required for tissue engineering include cells, growth factors and a scaffold material to support them. Three different materials (metals, ceramics, and polymers) can be used to create a scaffold suitable for bone regeneration. Several cell types have been investigated in combination with biomaterials. In this review, we describe the options available for bone regeneration, focusing on tissue engineering strategies based on the use of different biomaterials combined with cells and growth factors.
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Affiliation(s)
- Giulia Battafarano
- Bone Physiopathology Research Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy; (G.B.); (M.R.)
| | - Michela Rossi
- Bone Physiopathology Research Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy; (G.B.); (M.R.)
| | - Viviana De Martino
- Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, “Sapienza” University of Rome, 00161 Rome, Italy;
| | - Francesco Marampon
- Department of Radiotherapy, “Sapienza” University of Rome, 00161 Rome, Italy;
| | - Luca Borro
- Advanced Cardiovascular Imaging Unit, Department of Imaging, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (L.B.); (A.S.)
| | - Aurelio Secinaro
- Advanced Cardiovascular Imaging Unit, Department of Imaging, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (L.B.); (A.S.)
| | - Andrea Del Fattore
- Bone Physiopathology Research Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children’s Hospital, IRCCS, 00146 Rome, Italy; (G.B.); (M.R.)
- Correspondence: ; Tel.: +39-066-859-3740
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13
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Lin HD, Fong CY, Biswas A, Bongso A. Allogeneic human umbilical cord Wharton's jelly stem cells increase several-fold the expansion of human cord blood CD34+ cells both in vitro and in vivo. Stem Cell Res Ther 2020; 11:527. [PMID: 33298170 PMCID: PMC7724853 DOI: 10.1186/s13287-020-02048-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Accepted: 11/24/2020] [Indexed: 12/14/2022] Open
Abstract
Background The transplantation of human umbilical cord blood (UCB) CD34+ cells has been successfully used to treat hematological disorders but one major limitation has been the low cell numbers available. Mesenchymal stem cells (MSCs) lying within the bone marrow in vivo behave like a scaffold on which CD34+ cells interact and proliferate. We therefore evaluated the use of allogeneic MSCs from the human UC Wharton’s jelly (hWJSCs) as stromal support for the ex vivo expansion of CD34+ cells. Methods We performed an in-depth evaluation of the primitiveness, migration, adhesion, maturation, mitochondrial behavior, and pathway mechanisms of this platform using conventional assays followed by the evaluation of engraftment potential of the expanded CD34+ cells in an in vivo murine model. Results We demonstrate that hWJSCs and its conditioned medium (hWJSC-CM) support the production of significantly high fold changes of CD34+, CD34+CD133+, CD34+CD90+, CD34+ALDH+, CD34+CD45+, and CD34+CD49f+ cells after 7 days of interaction when compared to controls. In the presence of hWJSCs or hWJSC-CM, the CD34+ cells produced significantly more primitive CFU-GEMM colonies, HoxB4, and HoxA9 gene expression and lower percentages of CD34+CXCR4+ cells. There were also significantly higher N-cadherin+ cell numbers and increased cell migration in transwell migration assays. The CD34+ cells expanded with hWJSCs had significantly lower mitochondrial mass, mitochondrial membrane potential, and oxidative stress. Green Mitotracker-tagged mitochondria from CD34+ cells were observed lying within red CellTracker-tagged hWJSCs under confocal microscopy indicating mitochondrial transfer via tunneling nanotubes. CD34+ cells expanded with hWJSCs and hWJSC-CM showed significantly reduced oxidative phosphorylation (ATP6VIH and NDUFA10) and increased glycolytic (HIF-1a and HK-1) pathway-related gene expression. CD34+ cells expanded with hWJSCs for 7 days showed significant greater CD45+ cell chimerism in the bone marrow of primary and secondary irradiated mice when transplanted intravenously. Conclusions In this report, we confirmed that allogeneic hWJSCs provide an attractive platform for the ex vivo expansion of high fold numbers of UCB CD34+ cells while keeping them primitive. Allogeneic hWJSCs are readily available in abundance from discarded UCs, can be easily frozen in cord blood banks, thawed, and then used as a platform for UCB-HSC expansion if numbers are inadequate.
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Affiliation(s)
- Hao Daniel Lin
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Kent Ridge, 119228, Singapore
| | - Chui-Yee Fong
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Kent Ridge, 119228, Singapore
| | - Arijit Biswas
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Kent Ridge, 119228, Singapore
| | - Ariff Bongso
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Kent Ridge, 119228, Singapore.
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14
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Kalamegam G, Alfakeeh SM, Bahmaid AO, AlHuwait EA, Gari MA, Abbas MM, Ahmed F, Abu-Elmagd M, Pushparaj PN. In vitro Evaluation of the Anti-inflammatory Effects of Thymoquinone in Osteoarthritis and in silico Analysis of Inter-Related Pathways in Age-Related Degenerative Diseases. Front Cell Dev Biol 2020; 8:646. [PMID: 32793594 PMCID: PMC7391788 DOI: 10.3389/fcell.2020.00646] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Accepted: 06/29/2020] [Indexed: 12/12/2022] Open
Abstract
Chronic inflammation is a common underlying factor in osteoarthritis (OA) and most age-related degenerative diseases. As conventional therapies help only in partial alleviation of symptoms in OA, stem cell-based therapies and herbal supplements are being widely explored. Thymoquinone (TQ), an active ingredient of Nigella sativa is reported to have immunomodulatory, anti-inflammatory and antioxidant properties. We evaluated the effects of TQ on bone marrow MSCs (BM-MSCs) derived from OA patients and its interrelated pathways in inflammation and age-related degenerative diseases using Ingenuity Pathway Analysis (IPA) as well as possible molecular targets using SwissTargetPrediction. BM-MSCs were derived from OA patients and their stemness properties were characterized by studying the MSCs related CD surface marker expression and differentiation into adipocytes, osteoblasts, and chondrocytes. Treatment with TQ (100 nM-5 μM) demonstrated cell death, especially at higher concentrations. MTT assay demonstrated a significant concentration-dependent decrease in cell viability which ranged from 20.04% to 69.76% with higher doses (300 nM, 1 μM, and 5 μM), especially at 48h and 72h. Additional cell viability testing with CellTiter-Blue also demonstrated a significant concentration-dependent decrease in cell viability which ranged from 27.80 to 73.67% with higher doses (300 nM, 1 μM, 3 μM, and 5 μM). Gene expression analysis following treatment of BM-MSCs with TQ (1 and 3 μM) for 48h showed upregulation of the anti-inflammatory genes IL-4 and IL-10. In contrast, the pro-inflammatory genes namely IFN-γ, TNF-α, COX-2, IL-6, IL-8, IL-16, and IL-12A although were upregulated, compared to the lower concentration of TQ (1 μM) they were all decreased at 3 μM. The pro-apoptotic BAX gene was downregulated while the SURVIVIN gene was upregulated. IPA of the molecular interaction of TQ in inflammation and age-related degenerative diseases identified canonical pathways directly related to synaptogenesis, neuroinflammation, TGF-β, and interleukin signaling. Further screening led to the identification of 36 molecules that are involved in apoptosis, cell cycle regulation, cytokines, chemokines, and growth factors. SwissTargetPrediction of TQ identified potential molecular targets with high probability. TQ exerted anti-inflammatory effects and therefore can be a useful adjuvant along with conventional therapies against inflammation in OA and other age-related degenerative diseases.
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Affiliation(s)
- Gauthaman Kalamegam
- Stem Cells Unit, Centre of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.,Sheikh Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis by Stem Cells, King Abdulaziz University, Jeddah, Saudi Arabia.,Faculty of Medicine, Asian Institute of Medicine, Science and Technology, AIMST University, Bedong, Malaysia
| | - Saadiah M Alfakeeh
- Department of Biochemistry, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Afnan Omar Bahmaid
- Department of Biochemistry, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Etimad A AlHuwait
- Department of Biochemistry, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mamdouh A Gari
- Stem Cells Unit, Centre of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.,Sheikh Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis by Stem Cells, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mohammed M Abbas
- Sheikh Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis by Stem Cells, King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Orthopaedic Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Farid Ahmed
- Stem Cells Unit, Centre of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Muhammed Abu-Elmagd
- Stem Cells Unit, Centre of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Peter Natesan Pushparaj
- Stem Cells Unit, Centre of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
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15
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Changes in Stemness Properties, Differentiation Potential, Oxidative Stress, Senescence and Mitochondrial Function in Wharton's Jelly Stem Cells of Umbilical Cords of Mothers with Gestational Diabetes Mellitus. Stem Cell Rev Rep 2020; 15:415-426. [PMID: 30645713 DOI: 10.1007/s12015-019-9872-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Gestational diabetes mellitus (GDM) has been associated with an increased risk of maternal and neonatal morbidity. The Wharton's jelly (WJ) of the umbilical cord (UC) is a useful indicator of the deleterious effects of hyperglycemia on fetal tissues as it represents the fetus embryologically, physiologically and genetically. We studied WJ mesenchymal stem cells (hWJSCs) from UC from mothers without GDM (Normal; n = 3); insulin-controlled GDM mothers (GDMi; n = 3) and diet-controlled GDM mothers (GDMd; n = 3)]. Cell proliferation, stemness markers, telomerase, osteogenic and chondrogenic differentiation, antioxidant enzymes and gene expression for mitochondrial function (ND2, TFAM, PGC1α, and NDUFB9) were significantly lower in GDMi-hWJSCs and GDMd-hWJSCs compared to normal hWJSCs (P < 0.05). On the other hand, cell cycle inhibitors (p16, p21, p27) and p53 were remarkably up-regulated in GDMi-hWJSCs and GDMd-hWJSCs compared to normal hWJSCs. The results from this study confirmed that maternal hyperglycemia even though managed with insulin or diet, induced changes in the properties of the WJ and its cells. These changes may also be observed in fetal tissues and if true, prevention of the onset of gestational diabetes should be a priority over management. Generation of tissues that simulate those of the fetus such as pancreatic and cardiovascular cells from GDM-hWJSCs by direct differentiation or via induced pluripotent stem cell reprogramming provide possible platforms to evaluate the effects of glucose on specific fetal organ.
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16
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Chang YH, Wu KC, Wang CC, Ding DC. Enhanced chondrogenesis of human umbilical cord mesenchymal stem cells in a gelatin honeycomb scaffold. J Biomed Mater Res A 2020; 108:2069-2079. [PMID: 32323440 DOI: 10.1002/jbm.a.36966] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Revised: 03/19/2020] [Accepted: 03/28/2020] [Indexed: 12/16/2022]
Abstract
Transplantation of chondrogenic stem cells is a promising strategy for cartilage repair, but requires improvements in cell sourcing, maintenance, and chondrogenic differentiation efficiency. We examined whether gelatin honeycomb scaffolds can enhance the proliferation, viability, and chondrogenic capability of human umbilical cord mesenchymal stem cells (HUCMSCs) compared to standard plate cultures. In addition, the survival and phenotypic stability of HUCMSC-derived chondrocytes in a scaffold were evaluated in mice over 6 weeks post-transplantation. Survival and proliferation rates of HUCMSCs were comparable between scaffold and plate culture. Scaffold culture in a chondrogenic differentiation medium induced more stable expression of the key hyaline cartilage genes COL2A1 and ACAN and the production of the respective proteins Type II collagen and aggrecan as well as glycosaminoglycan. These HUCMSC-differentiated chondrocytes also stably expressed cartilage genes and proteins in the scaffold 6 weeks after transplantation into nonobese diabetic/severe combined immunodeficient mice. These findings indicate that honeycomb-like gelatin scaffolds can promote the survival and chondrogenic differentiation of HUCMSCs to form hyaline-like cartilage.
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Affiliation(s)
- Yu-Hsun Chang
- Department of Pediatrics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan
| | - Kun-Chi Wu
- Department of Orthopedics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan
| | - Chen-Chie Wang
- Department of Orthopedics, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, New Taipei City, Taiwan
| | - Dah-Ching Ding
- Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan.,Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.,Stem Cell Laboratory, Department of Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
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17
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Barati D, Gegg C, Yang F. Nanoparticle-Mediated TGF-β Release from Microribbon-Based Hydrogels Accelerates Stem Cell-Based Cartilage Formation In Vivo. Ann Biomed Eng 2020; 48:1971-1981. [PMID: 32377980 PMCID: PMC10155292 DOI: 10.1007/s10439-020-02522-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 04/24/2020] [Indexed: 04/04/2023]
Abstract
Conventional nanoporous hydrogels often lead to slow cartilage deposition by MSCs in 3D due to physical constraints and requirement for degradation. Our group has recently reported macroporous gelatin microribbon (μRB) hydrogels, which substantially accelerate MSC-based cartilage formation in vitro compared to conventional gelatin hydrogels. To facilitate translating the use of μRB-based scaffolds for supporting stem cell-based cartilage regeneration in vivo, there remains a need to develop a customize-designed drug delivery system that can be incorporated into μRB-based scaffolds. Towards this goal, here we report polydopamine-coated mesoporous silica nanoparticles (MSNs) that can be stably incorporated within the macroporous μRB scaffolds, and allow tunable release of transforming growth factor (TGF)-β3. We hypothesize that increasing concentration of polydopamine coating on MSNs will slow down TGF- β3 release, and TGF-β3 release from polydopamine-coated MSNs can enhance MSC-based cartilage formation in vitro and in vivo. We demonstrate that TGF-β3 released from MSNs enhance MSC-based cartilage regeneration in vitro to levels comparable to freshly added TGF-β3 in the medium, as shown by biochemical assays, mechanical testing, and histology. Furthermore, when implanted in vivo in a mouse subcutaneous model, only the group containing MSN-mediated TGF-β3 release supported continuous cartilage formation, whereas control group without MSN showed loss of cartilage matrix and undesirable endochondral ossification. The modular design of MSN-mediated drug delivery can be customized for delivering multiple drugs with individually optimized release kinetics, and may be applicable to enhance regeneration of other tissue types.
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Affiliation(s)
- Danial Barati
- Department of Orthopedic Surgery, Stanford University Schools of Engineering and Medicine, 300 Pasteur Drive, Edwards R105, Stanford, CA, 94305, USA
| | - Courtney Gegg
- Department of Bioengineering, Stanford University Schools of Engineering and Medicine, 300 Pasteur Drive, Edwards R105, Stanford, CA, 94305, USA
| | - Fan Yang
- Departments of Bioengineering and Orthopedic Surgery, Stanford University Schools of Engineering and Medicine, 300 Pasteur Drive, Edwards R105, Stanford, CA, 94305, USA.
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18
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3D Culture of MSCs on a Gelatin Microsphere in a Dynamic Culture System Enhances Chondrogenesis. Int J Mol Sci 2020; 21:ijms21082688. [PMID: 32294921 PMCID: PMC7215541 DOI: 10.3390/ijms21082688] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 04/04/2020] [Accepted: 04/07/2020] [Indexed: 12/17/2022] Open
Abstract
Recent advancement in cartilage tissue engineering has explored the potential of 3D culture to mimic the in vivo environment of human cartilaginous tissue. Three-dimensional culture using microspheres was described to play a role in driving the differentiation of mesenchymal stem cells to chondrocyte lineage. However, factors such as mechanical agitation on cell chondrogenesis during culture on the microspheres has yet to be elucidated. In this study, we compared the 2D and 3D culture of bone-marrow-derived mesenchymal stem cells (BMSCs) on gelatin microspheres (GMs) in terms of MSC stemness properties, immune-phenotype, multilineage differentiation properties, and proliferation rate. Then, to study the effect of mechanical agitation on chondrogenic differentiation in 3D culture, we cultured BMSCs on GM (BMSCs-GM) in either static or dynamic bioreactor system with two different mediums, i.e., F12: DMEM (1:1) + 10% FBS (FD) and chondrogenic induction medium (CIM). Our results show that BMSCs attached to the GM surface and remained viable in 3D culture. BMSCs-GM proliferated faster and displayed higher stemness properties than BMSCs on a tissue culture plate (BMSCs-TCP). GMs also enhanced the efficiency of in-vitro chondrogenesis of BMSCs, especially in a dynamic culture with higher cell proliferation, RNA expression, and protein expression compared to that in a static culture. To conclude, our results indicate that the 3D culture of BMSCs on gelatin microsphere was superior to 2D culture on a standard tissue culture plate. Furthermore, culturing BMSCs on GM in dynamic culture conditions enhanced their chondrogenic differentiation.
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Song JS, Hong KT, Kim NM, Park HS, Choi NH. Human umbilical cord blood-derived mesenchymal stem cell implantation for osteoarthritis of the knee. Arch Orthop Trauma Surg 2020; 140:503-509. [PMID: 31980879 DOI: 10.1007/s00402-020-03349-y] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Indexed: 01/07/2023]
Abstract
INTRODUCTION This study aimed to investigate the clinical outcomes after human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) implantation for medial compartment (MC) osteoarthritis of the knee. MATERIALS AND METHODS Inclusion criteria were patients older than 60 years, with a kissing lesion of the MC, a full-thickness chondral defect ≥ 4 cm2 of the medial femoral condyle (MFC), and a varus deformity ≥ 3° on a long cassette scanogram. The mean age was 64.9 ± 4.4 years and the mean chondral defect of the MFC was 7.2 ± 1.9 cm2. A mixture of sodium hyaluronate and hUCB-MSC was implanted into the chondral defect and a high tibial osteotomy was performed in all patients. International Knee Documentation Committee (IKDC), visual analog scale (VAS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were evaluated preoperatively and 1 year and 2 years postoperatively. Cartilage regeneration was evaluated in 14 (56%) patients by second-look arthroscopy at 1 year postoperatively. RESULTS Twenty-five patients underwent hUBC-MSC implantation. IKDC, VAS, and WOMAC scores at 1 year and 2 years improved significantly compared to preoperative scores. These scores at 1 year and 2 years were not significantly different between the body mass index (BMI) < 25 group and BMI ≥ 25 group. However, the < 65-year-old group showed superior IKDC scores at 1 year and 2 years and VAS score at 2 years than the ≥ 65-year-old group. Younger age and larger size of the chondral defect were associated with a significantly greater improvement in IKDC, VAS and WOMAC scores at 2 years. Second-look arthroscopy demonstrated International Cartilage Repair Society-Cartilage Repair Assessment grade I in six (42.9%) patients and grade II in eight (57.1%). CONCLUSIONS hUCB-MSC implantation regenerated cartilage satisfactorily and showed satisfactory clinical outcomes in patients older than 60 years who had MC osteoarthritis.
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Affiliation(s)
- Jun-Seob Song
- Department of Orthopaedic Surgery, Seoul JS Hospital, Seoul, South Korea
| | - Ki-Taek Hong
- Department of Orthopaedic Surgery, Seoul JS Hospital, Seoul, South Korea
| | - Na-Min Kim
- Department of Orthopaedic Surgery, Seoul JS Hospital, Seoul, South Korea
| | - Han-Soo Park
- Department of Orthopaedic Surgery, Seoul JS Hospital, Seoul, South Korea
| | - Nam-Hong Choi
- Department of Orthopaedic Surgery, Eulji Medical Center, Seoul, South Korea.
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20
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Garzon I, Chato-Astrain J, Campos F, Fernandez-Valades R, Sanchez-Montesinos I, Campos A, Alaminos M, D'Souza RN, Martin-Piedra MA. Expanded Differentiation Capability of Human Wharton's Jelly Stem Cells Toward Pluripotency: A Systematic Review. TISSUE ENGINEERING PART B-REVIEWS 2020; 26:301-312. [PMID: 32085697 DOI: 10.1089/ten.teb.2019.0257] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Human Wharton's jelly stem cells (HWJSC) can be efficiently isolated from the umbilical cord, and numerous reports have demonstrated that these cells can differentiate into several cell lineages. This fact, coupled with the high proliferation potential of HWJSC, makes them a promising source of stem cells for use in tissue engineering and regenerative medicine. However, their real potentiality has not been established to date. In the present study, we carried out a systematic review to determine the multilineage differentiation potential of HWJSC. After a systematic literature search, we selected 32 publications focused on the differentiation potential of these cells. Analysis of these studies showed that HWJSC display expanded differentiation potential toward some cell types corresponding to all three embryonic cell layers (ectodermal, mesodermal, and endodermal), which is consistent with their constitutive expression of key pluripotency markers such as OCT4, SOX2, and NANOG, and the embryonic marker SSEA4. We conclude that HWJSC can be considered cells in an intermediate state between multipotentiality and pluripotentiality, since their proliferation capability is not unlimited and differentiation to all cell types has not been demonstrated thus far. These findings support the clinical use of HWJSC for the treatment of diseases affecting not only mesoderm-type tissues but also other cell lineages. Impact statement Human Wharton's jelly stem cells (HWJSC) are mesenchymal stem cells that are easy to isolate and handle, and that readily proliferate. Their wide range of differentiation capabilities supports the view that these cells can be considered pluripotent. Accordingly, HWJSC are one of the most promising cell sources for clinical applications in advanced therapies.
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Affiliation(s)
- Ingrid Garzon
- Tissue Engineering Group, Department of Histology, School of Medicine, University of Granada, Granada, Spain.,ibs.GRANADA, Biohealth Institute, Granada, Spain
| | - Jesus Chato-Astrain
- Tissue Engineering Group, Department of Histology, School of Medicine, University of Granada, Granada, Spain.,ibs.GRANADA, Biohealth Institute, Granada, Spain
| | - Fernando Campos
- Tissue Engineering Group, Department of Histology, School of Medicine, University of Granada, Granada, Spain.,ibs.GRANADA, Biohealth Institute, Granada, Spain
| | - Ricardo Fernandez-Valades
- ibs.GRANADA, Biohealth Institute, Granada, Spain.,Division of Pediatric Surgery, University of Granada Hospital Complex, Granada, Spain
| | - Indalecio Sanchez-Montesinos
- ibs.GRANADA, Biohealth Institute, Granada, Spain.,Department of Human Anatomy and Embryology, School of Medicine, University of Granada, Granada, Spain
| | - Antonio Campos
- Tissue Engineering Group, Department of Histology, School of Medicine, University of Granada, Granada, Spain.,ibs.GRANADA, Biohealth Institute, Granada, Spain
| | - Miguel Alaminos
- Tissue Engineering Group, Department of Histology, School of Medicine, University of Granada, Granada, Spain.,ibs.GRANADA, Biohealth Institute, Granada, Spain
| | - Rena N D'Souza
- Department of Dentistry, School of Dentistry, University of Utah, Salt Lake City, Utah, USA
| | - Miguel A Martin-Piedra
- Tissue Engineering Group, Department of Histology, School of Medicine, University of Granada, Granada, Spain.,ibs.GRANADA, Biohealth Institute, Granada, Spain
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21
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Arjunan S, Gan SU, Choolani M, Raj V, Lim J, Biswas A, Bongso A, Fong CY. Inhibition of growth of Asian keloid cells with human umbilical cord Wharton's jelly stem cell-conditioned medium. Stem Cell Res Ther 2020; 11:78. [PMID: 32085797 PMCID: PMC7035736 DOI: 10.1186/s13287-020-01609-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 02/11/2020] [Accepted: 02/14/2020] [Indexed: 02/06/2023] Open
Abstract
Background Keloid formation occurs in Caucasian, African, and Asian populations and is a severe psychosocial burden on patients. There is no permanent treatment for this problem as its pathogenesis is not properly understood. Furthermore, differences in keloid behavior between ethnic groups are not known. It has been hypothesized that keloids behave like benign tumors because of their uncontrolled growth. The present study evaluated the tumoricidal properties of human Wharton’s jelly stem cell-conditioned medium (hWJSC-CM) on fresh Asian keloid cells (AKCs). Methods Human Wharton’s jelly stem cells (hWJSCs) and AKCs were isolated based on our previous methods. hWJSCs and human skin fibroblasts (HSF) (controls) were used to collect hWJSC-CM and HSF-conditioned medium (HSF-CM). AKCs were treated with hWJSC-CM and HSF-CM in vitro and in vivo in a human keloid xenograft SCID mouse model. The inhibitory effect of hWJSC-CM on AKCs was tested in vitro using various assays and in vivo for attenuation/abrogation of AKC tumors created in a xenograft mouse model. Results qRT-PCR analysis showed that the genes FN1, MMP1, and VCAN were significantly upregulated in AKCs and ANXA1, ASPN, IGFBP7, LGALS1, and PTN downregulated. AKCs exposed to hWJSC-CM in vitro showed significant decreases in cell viability and proliferation, increases in Annexin V-FITC+ cell numbers, interruptions of the cell cycle at Sub-G1 and G2/M phases, altered CD marker expression, downregulated anti-apoptotic-related genes, and upregulated pro-apoptotic and autophagy-related genes compared to controls. When AKCs were administered together with hWJSC-CM into immunodeficient mice there were no keloid tumors formed in 7 mice (n = 10) compared to the untreated control mice. When hWJSC-CM was injected directly into keloid tumors created in mice there were significant reductions in keloid tumor volumes and weights in 30 days. Conclusions hWJSC-CM inhibited the growth of AKCs in vitro and in xenograft mice, and it may be a potential novel treatment for keloids in the human. The specific molecule(s) in hWJSC-CM that induce the anti-keloid effect need to be identified, characterized, and tested separately in larger preclinical and clinical studies.
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Affiliation(s)
- Subramanian Arjunan
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Kent Ridge, 119228, Singapore
| | - Shu Uin Gan
- Department of Surgery, Kent Ridge, 119228, Singapore
| | - Mahesh Choolani
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Kent Ridge, 119228, Singapore
| | - Vaishnevi Raj
- Department of Medicine, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Kent Ridge, 119228, Singapore
| | - Jane Lim
- Department of Surgery, Kent Ridge, 119228, Singapore
| | - Arijit Biswas
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Kent Ridge, 119228, Singapore
| | - Ariff Bongso
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Kent Ridge, 119228, Singapore
| | - Chui Yee Fong
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Kent Ridge, 119228, Singapore.
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22
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Jafri MA, Kalamegam G, Abbas M, Al-Kaff M, Ahmed F, Bakhashab S, Rasool M, Naseer MI, Sinnadurai V, Pushparaj PN. Deciphering the Association of Cytokines, Chemokines, and Growth Factors in Chondrogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Using an ex vivo Osteochondral Culture System. Front Cell Dev Biol 2020; 7:380. [PMID: 32010693 PMCID: PMC6979484 DOI: 10.3389/fcell.2019.00380] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Accepted: 12/17/2019] [Indexed: 12/20/2022] Open
Abstract
Osteoarthritis (OA) is a chronic degenerative joint disorder associated with degradation and decreased production of the extracellular matrix, eventually leading to cartilage destruction. Limited chondrocyte turnover, structural damage, and prevailing inflammatory milieu prevent efficient cartilage repair and restoration of joint function. In the present study, we evaluated the role of secreted cytokines, chemokines, and growth factors present in the culture supernatant obtained from an ex vivo osteochondral model of cartilage differentiation using cartilage pellets (CP), bone marrow stem cells (BM-MSCs), and/or BM-MSCs + CP. Multiplex cytokine analysis showed differential secretion of growth factors (G-CSF, GM-CSF, HGF, EGF, VEGF); chemokines (MCP-1, MIP1α, MIP1β, RANTES, Eotaxin, IP-10), pro-inflammatory cytokines (IL-1β, IL-2, IL-5, IL-6, IL-8, TNFα, IL-12, IL-15, IL-17) and anti-inflammatory cytokines (IL-4, IL-10, and IL-13) in the experimental groups compared to the control. In silico analyses of the role of stem cells and CP in relation to the expression of various molecules, canonical pathways and hierarchical cluster patterns were deduced using the Ingenuity Pathway Analysis (IPA) software (Qiagen, United States). The interactions of the cytokines, chemokines, and growth factors that are involved in the cartilage differentiation showed that stem cells, when used together with CP, bring about a favorable cell signaling that supports cartilage differentiation and additionally helps to attenuate inflammatory cytokines and further downstream disease-associated pro-inflammatory pathways. Hence, the autologous or allogeneic stem cells and local cartilage tissues may be used for efficient cartilage differentiation and the management of OA.
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Affiliation(s)
- Mohammad Alam Jafri
- Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Gauthaman Kalamegam
- Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.,Sheikh Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis by Stem Cells, King Abdulaziz University, Jeddah, Saudi Arabia.,Faculty of Medicine, Asian Institute of Medicine, Science and Technology University, Bedong, Malaysia
| | - Mohammed Abbas
- Sheikh Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis by Stem Cells, King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Orthopaedic Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mohammed Al-Kaff
- Sheikh Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis by Stem Cells, King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Orthopaedic Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Farid Ahmed
- Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Sherin Bakhashab
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mahmood Rasool
- Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Muhammad Imran Naseer
- Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Vasan Sinnadurai
- Faculty of Medicine, Asian Institute of Medicine, Science and Technology University, Bedong, Malaysia
| | - Peter Natesan Pushparaj
- Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
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23
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Affiliation(s)
- Jiahui Zhang
- Mechanical and Automotive Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
| | - Yihua Feng
- Mechanical and Automotive Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
| | - Xuan Zhou
- Mechanical and Automotive Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
| | - Yanbin Shi
- Mechanical and Automotive Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
| | - Li Wang
- Mechanical and Automotive Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
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24
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Ma R, Schär M, Chen T, Wang H, Wada S, Ju X, Deng XH, Rodeo SA. Use of Human Placenta-Derived Cells in a Preclinical Model of Tendon Injury. J Bone Joint Surg Am 2019; 101:e61. [PMID: 31274724 DOI: 10.2106/jbjs.15.01381] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Emerging data suggest that human cells derived from extraembryonic tissues may have favorable musculoskeletal repair properties. The purpose of this study was to determine whether the injection of human placenta-derived mesenchymal-like stromal cells, termed placental expanded cells (PLX-PAD), would improve tendon healing in a preclinical model of tendinopathy. METHODS Sixty male Sprague-Dawley rats underwent bilateral patellar tendon injection with either saline solution (control) or PLX-PAD cells (2 × 10 cells/100 µL) 6 days after collagenase injection to induce tendon degeneration. Animals were killed at specific time points for biomechanical, histological, and gene expression analyses of the healing patellar tendons. RESULTS Biomechanical testing 2 weeks after the collagenase injury demonstrated better biomechanical properties in the tendons treated with PLX-PAD cells. The load to failure of the PLX-PAD-treated tendons was higher than that of the saline-solution-treated controls at 2 weeks (77.01 ± 10.51 versus 58.87 ± 11.97 N, p = 0.01). There was no significant difference between the 2 groups at 4 weeks. There were no differences in stiffness at either time point. Semiquantitative histological analysis demonstrated no significant differences in collagen organization or cellularity between the PLX-PAD and saline-solution-treated tendons. Gene expression analysis demonstrated higher levels of interleukin-1β (IL-1β) and IL-6 early in the healing process in the PLX-PAD-treated tendons. CONCLUSIONS Human placenta-derived cell therapy induced an early inflammatory response and a transient beneficial effect on tendon failure load in a model of collagenase-induced tendon degeneration. CLINICAL RELEVANCE Human extraembryonic tissues, such as the placenta, are an emerging source of cells for musculoskeletal repair and may hold promise as a point-of-care cell therapy for tendon injuries.
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Affiliation(s)
- Richard Ma
- Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri
| | - Michael Schär
- Sports Medicine and Shoulder Service, The Hospital for Special Surgery, New York, NY
| | - Tina Chen
- Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri
| | - Hongsheng Wang
- Sports Medicine and Shoulder Service, The Hospital for Special Surgery, New York, NY
| | - Susumu Wada
- Sports Medicine and Shoulder Service, The Hospital for Special Surgery, New York, NY
| | - Xiadong Ju
- Sports Medicine and Shoulder Service, The Hospital for Special Surgery, New York, NY
| | - Xiang-Hua Deng
- Sports Medicine and Shoulder Service, The Hospital for Special Surgery, New York, NY
| | - Scott A Rodeo
- Sports Medicine and Shoulder Service, The Hospital for Special Surgery, New York, NY
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25
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Raj V, Claudine S, Subramanian A, Tam K, Biswas A, Bongso A, Fong CY. Histological, immunohistochemical, and genomic evaluation of excisional and diabetic wounds treated with human Wharton's jelly stem cells with and without a nanocarrier. J Cell Biochem 2019; 120:11222-11240. [PMID: 30706534 DOI: 10.1002/jcb.28398] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Revised: 12/15/2018] [Accepted: 01/10/2019] [Indexed: 01/24/2023]
Abstract
We showed in previous studies that human umbilical cord Wharton's jelly stem cells (hWJSCs) improved the healing rates of excisional and diabetic wounds in the mouse model. As an extension of those studies, we report here the more detailed quantitative histological, immunohistochemical, and genomic evaluation of biopsies from those excisional and diabetic wounds in an attempt to understand the mechanisms of the enhanced wound healing aided by hWJSCs. Bright-field microscopic observations and ImageJ software analysis on histological sections of the excisional and diabetic wound biopsies collected at different time points showed that the thickness of the epidermis and dermis, and positive picrosirius-red stained areas for collagen, were significantly greater in the presence of hWJSCs compared with controls (P < 0.05). Immunohistochemistry of the diabetic wound biopsies showed increased positive staining for the vascular endothelial marker CD31 and cell proliferation marker Ki67 in the presence of hWJSCs and its conditioned medium (hWJSC-CM). Quantitative real-time polymerase chain reaction showed upregulation of groups of genes involved in extracellular matrix regulation, collagen biosynthesis, angiogenesis, antifibrosis, granulation, and immunomodulation in the presence of hWJSCs. Taken together, the results demonstrated that hWJSCs and hWJSC-CM that contains the paracrine secretions of hWJSCs, enhance the healing of excisional and diabetic wounds via re-epithelialization, collagen deposition, angiogenesis, and immunomodulation. The inclusion of an Aloe vera-polycaprolactone (AV/PCL) nanocarrier did not significantly change the effect of the hWJSCs. However, the topical application of an AV/PCL nanocarrier impregnated with hWJSCs is convenient and less invasive than the administration of hWJSC injections into wounds.
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Affiliation(s)
- Vaishnevi Raj
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore
| | - Stephanie Claudine
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore
| | - Arjunan Subramanian
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore
| | - Kimberley Tam
- BioSystems and Micromechanics IRG, Singapore-MIT Alliance in Research and Technology, Singapore
| | - Arijit Biswas
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore
| | - Ariff Bongso
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore
| | - Chui-Yee Fong
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore
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Mazini L, Rochette L, Amine M, Malka G. Regenerative Capacity of Adipose Derived Stem Cells (ADSCs), Comparison with Mesenchymal Stem Cells (MSCs). Int J Mol Sci 2019; 20:ijms20102523. [PMID: 31121953 PMCID: PMC6566837 DOI: 10.3390/ijms20102523] [Citation(s) in RCA: 262] [Impact Index Per Article: 43.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 05/03/2019] [Accepted: 05/06/2019] [Indexed: 12/13/2022] Open
Abstract
Adipose tissue is now on the top one of stem cell sources regarding its accessibility, abundance, and less painful collection procedure when compared to other sources. The adipose derived stem cells (ADSCs) that it contains can be maintained and expanded in culture for long periods of time without losing their differentiation capacity, leading to large cell quantities being increasingly used in cell therapy purposes. Many reports showed that ADSCs-based cell therapy products demonstrated optimal efficacy and efficiency in some clinical indications for both autologous and allogeneic purposes, hence becoming considered as potential tools for replacing, repairing, and regenerating dead or damaged cells. In this review, we analyzed the therapeutic advancement of ADSCs in comparison to bone marrow (BM) and umbilical cord (UC)-mesenchymal stem cells (MSCs) and designed the specific requirements to their best clinical practices and safety. Our analysis was focused on the ADSCs, rather than the whole stromal vascular fraction (SVF) cell populations, to facilitate characterization that is related to their source of origins. Clinical outcomes improvement suggested that these cells hold great promise in stem cell-based therapies in neurodegenerative, cardiovascular, and auto-immunes diseases.
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Affiliation(s)
- Loubna Mazini
- Laboratoire Cellules Souches et Ingénierie Tissulaire, Centre Interface Applications Médicales CIAM, Université Mohammed VI polytechnique, Ben Guérir 43150, Morocco.
| | - Luc Rochette
- Equipe d'Accueil (EA 7460), Physiopathologie et Epidémiologie Cérébro-Cardiovasculaires (PEC2), Université de Bourgogne Franche Comté, Faculté des Sciences de Santé, 7 Bd Jeanne d'Arc, 21000 Dijon, France.
| | - Mohamed Amine
- Laboratoire d'Epidémiologie et de Biostatique, Centre Interface Applications Médicales CIAM, Université Mohammed VI polytechnique, Ben Guérir 43150, Morocco.
- Département de Santé Publique et de Médecine Communautaire, Faculté de Médecine et de Pharmacie, Université Cadi Ayyad, Marrakech 40000, Morocco.
| | - Gabriel Malka
- Laboratoire Cellules Souches et Ingénierie Tissulaire, Centre Interface Applications Médicales CIAM, Université Mohammed VI polytechnique, Ben Guérir 43150, Morocco.
- Laboratoire d'Epidémiologie et de Biostatique, Centre Interface Applications Médicales CIAM, Université Mohammed VI polytechnique, Ben Guérir 43150, Morocco.
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27
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Mazini L, Rochette L, Amine M, Malka G. Regenerative Capacity of Adipose Derived Stem Cells (ADSCs), Comparison with Mesenchymal Stem Cells (MSCs). Int J Mol Sci 2019. [PMID: 31121953 DOI: 10.3390/ijms20102523.pmid:31121953;pmcid:pmc6566837] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023] Open
Abstract
Adipose tissue is now on the top one of stem cell sources regarding its accessibility, abundance, and less painful collection procedure when compared to other sources. The adipose derived stem cells (ADSCs) that it contains can be maintained and expanded in culture for long periods of time without losing their differentiation capacity, leading to large cell quantities being increasingly used in cell therapy purposes. Many reports showed that ADSCs-based cell therapy products demonstrated optimal efficacy and efficiency in some clinical indications for both autologous and allogeneic purposes, hence becoming considered as potential tools for replacing, repairing, and regenerating dead or damaged cells. In this review, we analyzed the therapeutic advancement of ADSCs in comparison to bone marrow (BM) and umbilical cord (UC)-mesenchymal stem cells (MSCs) and designed the specific requirements to their best clinical practices and safety. Our analysis was focused on the ADSCs, rather than the whole stromal vascular fraction (SVF) cell populations, to facilitate characterization that is related to their source of origins. Clinical outcomes improvement suggested that these cells hold great promise in stem cell-based therapies in neurodegenerative, cardiovascular, and auto-immunes diseases.
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Affiliation(s)
- Loubna Mazini
- Laboratoire Cellules Souches et Ingénierie Tissulaire, Centre Interface Applications Médicales CIAM, Université Mohammed VI polytechnique, Ben Guérir 43150, Morocco.
| | - Luc Rochette
- Equipe d'Accueil (EA 7460), Physiopathologie et Epidémiologie Cérébro-Cardiovasculaires (PEC2), Université de Bourgogne Franche Comté, Faculté des Sciences de Santé, 7 Bd Jeanne d'Arc, 21000 Dijon, France.
| | - Mohamed Amine
- Laboratoire d'Epidémiologie et de Biostatique, Centre Interface Applications Médicales CIAM, Université Mohammed VI polytechnique, Ben Guérir 43150, Morocco.
- Département de Santé Publique et de Médecine Communautaire, Faculté de Médecine et de Pharmacie, Université Cadi Ayyad, Marrakech 40000, Morocco.
| | - Gabriel Malka
- Laboratoire Cellules Souches et Ingénierie Tissulaire, Centre Interface Applications Médicales CIAM, Université Mohammed VI polytechnique, Ben Guérir 43150, Morocco.
- Laboratoire d'Epidémiologie et de Biostatique, Centre Interface Applications Médicales CIAM, Université Mohammed VI polytechnique, Ben Guérir 43150, Morocco.
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Wu KC, Chang YH, Liu HW, Ding DC. Transplanting human umbilical cord mesenchymal stem cells and hyaluronate hydrogel repairs cartilage of osteoarthritis in the minipig model. Tzu Chi Med J 2019; 31:11-19. [PMID: 30692826 PMCID: PMC6334562 DOI: 10.4103/tcmj.tcmj_87_18] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Revised: 01/15/2018] [Accepted: 04/21/2018] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVES Osteoarthritis (OA) is a chronic disease of degenerative joints. Mesenchymal stem cells (MSCs) have been used for cartilage regeneration in OA. We investigated the therapeutic potential of human umbilical cord-derived MSCs (HUCMSCs) with hyaluronic acid (HA) hydrogel transplanted into a porcine OA preclinical model. MATERIALS AND METHODS The HUCMSCs were characterized with respect to morphology, surface markers, and differentiation capabilities. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was used to examine gene expressions in a HUCMSC-HA coculture. Two healthy female minipigs weighing 30-40 kg and aged approximately 4 months were used in this large animal study. A full-thickness chondral injury was created in the trochlear groove of each of the pig's rear knees. After 3 weeks, a second osteochondral defect was created. Then, 1.5 mL of a HUCMSC (5 × 106 cells) and HA composite (4%) was transplanted into the chondral-injured area in the right knee of each pig. Using the same surgical process, an osteochondral defect (untreated) was created in the left knee as a control. The pigs were sacrificed 12 weeks after transplantation. Macroscopic and microscopic histologies, qRT-PCR, and immunostaining evaluated the degree of chondral degradation. RESULTS The HUCMSCs exhibited typical MSC characteristics, including spindle morphology, expression of surface markers (positive for CD29, CD4, CD73, CD90, and human leukocyte antigen [HLA]-ABC; negative for CD34, CD45, and HLA-DR), and multipotent differentiation (adipogenesis, osteogenesis, and chondrogenesis). More extensive proliferation of HUCMSCs was noted with 4% and 25% of HA than without HA. Expression of COL2A1 and aggrecan in the HUCMSC-derived chondrocytes was increased when HA was included. The treated knees showed significant gross and histological improvements in hyaline cartilage regeneration when compared to the control knees. The International Cartilage Repair Society histological score was higher for the treated knees than the control knees. CONCLUSION Our findings suggest that cartilage regeneration using a mixture of HUCMSCs and HA in a large animal model may be an effective treatment for OA, and this study is a stepping stone toward the future clinical trials.
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Affiliation(s)
- Kun-Chi Wu
- Department of Orthopedics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Yu-Hsun Chang
- Department of Pediatrics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Hwan-Wun Liu
- Department of Occupational Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
- Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
| | - Dah-Ching Ding
- Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
- Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
- Department of Research, Stem Cell Laboratory, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
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Zhang Y, Liu S, Guo W, Wang M, Hao C, Gao S, Zhang X, Li X, Chen M, Jing X, Wang Z, Peng J, Lu S, Guo Q. Human umbilical cord Wharton's jelly mesenchymal stem cells combined with an acellular cartilage extracellular matrix scaffold improve cartilage repair compared with microfracture in a caprine model. Osteoarthritis Cartilage 2018; 26:954-965. [PMID: 29391278 DOI: 10.1016/j.joca.2018.01.019] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Revised: 01/16/2018] [Accepted: 01/22/2018] [Indexed: 02/07/2023]
Abstract
OBJECTIVE As a novel and promising seed cell, human umbilical cord Wharton's jelly mesenchymal stem cells (hWJMSCs) are widely applied in tissue engineering. However, whether hWJMSCs can better repair and regenerate the articular cartilage in big animals than microfracture (MF, a predominant clinical treatment strategy for damaged cartilage) is unclear. Evaluation of the validity, and safety of hWJMSCs in a caprine model with a full-thickness femoral condyle articular cartilage defect, compared with MF is required. METHODS After cultivation and identification, hWJMSCs were seeded in an acellular cartilage extracellular matrix (ACECM)-oriented scaffold to construct cell-scaffold complex. Six goats with full-thickness femoral condyle articular cartilage defects were randomized to MF (microfracture group, MFG) and cell-scaffold complexes (experimental group, EG). At 2 and 4 weeks, joint fluid was used to assess immuno-inflammatory responses. At 6 and 9 months, all goats were euthanized for assessment of morphology, and magnetic resonance imaging (MRI), histology staining, and evaluation of the elasticity modulus and glycosaminoglycan (GAG) contents of the repaired regions. RESULTS There were no significant differences between the two groups in immuno-inflammatory parameters. MRI demonstrated higher-quality cartilage and complete subchondral bone at defect sites in the EG at 9 months. Histological staining showed that extracellular cartilage, cartilage lacuna and collagen type II levels were higher in the EG compared to the MFG, while the EG exhibited a higher elasticity modulus. CONCLUSIONS The hWJMSCs-ACECM scaffold complex achieved better quality repair and regeneration of hyaline cartilage without cartilage-inducing factor, while retaining the structure and functional integrity of the subchondral bone, compared with MF.
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Affiliation(s)
- Y Zhang
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, 28 Fuxing Road, Haidian District, Beijing 100853, China; Institute of Orthopaedics, Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Gulou District, Nanjing 210008, China
| | - S Liu
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - W Guo
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - M Wang
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - C Hao
- Institute of Anesthesia, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - S Gao
- Academy for Advanced Interdisciplinary Studies, Peking University, No. 5 Yiheyuan Road, Haidian District, Beijing CN 154007, China
| | - X Zhang
- Shanxi Traditional Chinese, No. 46 Binzhou West Street, YingZe District, Taiyuan 030001, China
| | - X Li
- School of Medicine, Naikai University, Tianjin 300071, China
| | - M Chen
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - X Jing
- First Department of Orthopedics, First Affiliated Hospital of Jiamusi University, Jiamusi 154007, China
| | - Z Wang
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - J Peng
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - S Lu
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, 28 Fuxing Road, Haidian District, Beijing 100853, China
| | - Q Guo
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, 28 Fuxing Road, Haidian District, Beijing 100853, China.
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Chang YH, Wu KC, Liu HW, Chu TY, Ding DC. Human umbilical cord-derived mesenchymal stem cells reduce monosodium iodoacetate-induced apoptosis in cartilage. Tzu Chi Med J 2018; 30:71-80. [PMID: 29875586 PMCID: PMC5968746 DOI: 10.4103/tcmj.tcmj_23_18] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Revised: 09/04/2017] [Accepted: 09/08/2017] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVE The present study investigated the therapeutic potential and underlying mechanisms of human umbilical cord mesenchymal stem cells (HUCMSCs) on joint cartilage destruction induced by monosodium iodoacetate (MIA) in mice. MATERIALS AND METHODS HUCMSCs were tested for mesenchymal stem cell (MSC) characteristics including surface markers by flow cytometry and mesoderm differentiation (adipogenesis, osteogenesis, and chondrogenesis). Terminal deoxynucleotidyl transferase dUTP nick end labeling assay and Western blot assay were used to evaluate MIA-induced chondrocyte apoptosis. In the in vivo study, 18 mice were divided into three groups (n = 6 each); normal saline (control), MIA-treated, and MIA-treated/HUCMSC-transplantation. Rota-Rods tests were used to evaluate MIA-induced cartilage destruction behaviors in mice. Histological changes in the mice cartilage were examined by immunohistochemistry. RESULTS HUCMSCs had an immunophenotype similar to bone marrow-derived MSCs and were able to differentiate into adipocytes, osteocytes, and chondrocytes. Conditioned medium of the HUCMSCs exhibited an anti-apoptotic effect and inhibited expression of caspase 3 in MIA-treated chondrocytes. HUCMSC transplantation assisted in recovery from movement impairment (from 30% on day 7 to 115% on day 14) and in regeneration and repair of cartilage damaged by MIA. (International Cartilage Repair Society score: 3.8 in the MIA group vs. 10.2 in the HUCMSC-treated group); HUCMSC transplantation ameliorated cartilage apoptosis through the caspase 3 pathway in MIA-induced cartilage destruction in mice. CONCLUSION Taken together, these observations suggest that HUCMSC transplantation appears to be effective in protecting cartilage from MIA damage.
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Affiliation(s)
- Yu-Hsun Chang
- Department of Pediatrics, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
- Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
| | - Kun-Chi Wu
- Department of Orthopedics, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan
| | - Hwan-Wun Liu
- Department of Occupational Medicine, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan
| | - Tang-Yuan Chu
- Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
- Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan
| | - Dah-Ching Ding
- Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
- Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan
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Al-Yamani A, Kalamegam G, Ahmed F, Abbas M, Sait KHW, Anfinan N, Al-Wasiyah MK, Huwait EA, Gari M, Al-Qahtani M. Evaluation of in vitro chondrocytic differentiation: A stem cell research initiative at the King Abdulaziz University, Kingdom of Saudi Arabia. Bioinformation 2018; 14:53-59. [PMID: 29618900 PMCID: PMC5879944 DOI: 10.6026/97320630014053] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Revised: 02/01/2018] [Accepted: 02/01/2018] [Indexed: 12/15/2022] Open
Abstract
Mesenchymal stem cells (MSCs) from various sources have been used in cartilage differentiation with variable success. Therefore, it is
of interest to evaluate the in vitro differentiation potential of the hWJSCs derived from the human umbilical cords into chondrocytes at
the stem cell research facility at the King Abdulaziz University. hWJSCs are an attractive choice for tissue engineering and regenerative
medical applications including cartilage regeneration. We evaluated the hWJSCs using classical histological and cartilage related gene
expression studies. Some of the known parameters were re-examined for consistency at the current laboratory conditions. Early
passages (P1-P4) showed short fibroblastic morphology and high expression of MSC related surface markers namely CD29 (99.9%),
CD44 (97.8%), CD73 (99.6%), CD90 (95.1%) and CD105 (98.9%). MTT assay showed time dependent increase in hWJSCs proliferation by
61.06% and 206.31% at 48h and 72h respectively. Toluidine blue histology showed that hWJSCs were successfully differentiated into
chondrocytes in chondrocytic differentiation medium for 21 days. Differentiated hWJSCs also showed significantly increased
expression of collagen type II, aggrecan and SOX9 compared to the undifferentiated control. It should be noted that the determination
of the average cell yield, the population doubling time and histological staining wtih alcian blue and/or safronin O is required in future
studies for improved evaluation of differentiation. Painless derivation, abundance of stem cells that are hypo-immunogenic and safety
issues makes this method advantages to MSCs derived from other sources.
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Affiliation(s)
- Aisha Al-Yamani
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
| | - Gauthaman Kalamegam
- Stem Cell Unit, Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.,Sheikh Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis by Stem Cells, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Farid Ahmed
- Stem Cell Unit, Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mohammed Abbas
- Sheikh Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis by Stem Cells, King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Orthopaedic Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Khalid Hussein Wali Sait
- Department of Obstetrics and Gynaecology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Nisreen Anfinan
- Department of Obstetrics and Gynaecology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mohammad Khalid Al-Wasiyah
- Stem Cell Unit, Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Etimad A Huwait
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
| | - Mamdouh Gari
- Stem Cell Unit, Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
| | - Mohammed Al-Qahtani
- Stem Cell Unit, Centre of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia
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Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures. Stem Cells Int 2018. [PMID: 29535784 PMCID: PMC5832141 DOI: 10.1155/2018/9079538] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain uncertain. Stem cells can contribute to cartilage repair via chondrogenic differentiation, via immunomodulation, or by the production of paracrine factors and extracellular vesicles. But before novel cell-based therapies for cartilage repair can be introduced into the clinic, rigorous testing in preclinical animal models is required. Preclinical models used in regenerative cartilage studies include murine, lapine, caprine, ovine, porcine, canine, and equine models, each associated with its specific advantages and limitations. This review presents a summary of recent in vitro data and from in vivo preclinical studies justifying the use of MSCs and iPSCs in cartilage tissue engineering. Moreover, the advantages and disadvantages of utilizing small and large animals will be discussed, while also describing suitable outcome measures for evaluating cartilage repair.
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Kalamegam G, Memic A, Budd E, Abbas M, Mobasheri A. A Comprehensive Review of Stem Cells for Cartilage Regeneration in Osteoarthritis. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1089:23-36. [PMID: 29725971 DOI: 10.1007/5584_2018_205] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Osteoarthritis (OA) is an age related joint disease associated with degeneration and loss of articular cartilage. Consequently, OA patients suffer from chronic joint pain and disability. Weight bearing joints and joints that undergo repetitive stress and excessive 'wear and tear' are particularly prone to developing OA. Cartilage has a poor regenerative capacity and current pharmacological agents only provide symptomatic pain relief. OA patients that respond poorly to conventional therapies are ultimately treated with surgical procedures to promote cartilage repair by implantation of artificial joint structures (arthroplasty) or total joint replacement (TJR). In the last two decades, stem cells derived from various tissues with varying differentiation and tissue regeneration potential have been used for the treatment of OA either alone or in combination with natural or synthetic scaffolds to aid cartilage repair. Although stem cells can be differentiated into chondrocytes in vitro or aid cartilage regeneration in vivo, their potential for OA management remains limited as cartilage regenerated by stem cells fails to fully recapitulate the structural and biomechanical properties of the native tissue. Efficient tissue regeneration remains elusive despite the simple design of cartilage, which unlike most other tissues is avascular and aneural, consisting of a single cell type. In this article, we have comprehensively reviewed the types of stem cells that have been proposed or tested for the management of OA, their potential efficacy as well as their limitations. We also touch on the role of biomaterials in cartilage tissue engineering and examine the prospects for their use in cell-based therapies.
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Affiliation(s)
- Gauthaman Kalamegam
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.,Sheikh Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis with Stem Cells, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Adnan Memic
- Center of Nanotechnology, King AbdulAziz University, Jeddah, Saudi Arabia
| | - Emma Budd
- Department of Veterinary Pre-Clinical Sciences, School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Mohammed Abbas
- Sheikh Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis with Stem Cells, King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Orthopaedic Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ali Mobasheri
- Sheikh Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis with Stem Cells, King Abdulaziz University, Jeddah, Saudi Arabia. .,Department of Veterinary Pre-Clinical Sciences, School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK. .,Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, Queen's Medical Centre, Nottingham, UK. .,Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania.
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Allogeneic Umbilical Cord-Derived Mesenchymal Stem Cells as a Potential Source for Cartilage and Bone Regeneration: An In Vitro Study. Stem Cells Int 2017; 2017:1732094. [PMID: 29358953 PMCID: PMC5735324 DOI: 10.1155/2017/1732094] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2017] [Revised: 10/02/2017] [Accepted: 10/11/2017] [Indexed: 02/06/2023] Open
Abstract
Umbilical cord (UC) may represent an attractive cell source for allogeneic mesenchymal stem cell (MSC) therapy. The aim of this in vitro study is to investigate the chondrogenic and osteogenic potential of UC-MSCs grown onto tridimensional scaffolds, to identify a possible clinical relevance for an allogeneic use in cartilage and bone reconstructive surgery. Chondrogenic differentiation on scaffolds was confirmed at 4 weeks by the expression of sox-9 and type II collagen; low oxygen tension improved the expression of these chondrogenic markers. A similar trend was observed in pellet culture in terms of matrix (proteoglycan) production. Osteogenic differentiation on bone-graft-substitute was also confirmed after 30 days of culture by the expression of osteocalcin and RunX-2. Cells grown in the hypertrophic medium showed at 5 weeks safranin o-positive stain and an increased CbFa1 expression, confirming the ability of these cells to undergo hypertrophy. These results suggest that the UC-MSCs isolated from minced umbilical cords may represent a valuable allogeneic cell population, which might have a potential for orthopaedic tissue engineering such as the on-demand cell delivery using chondrogenic, osteogenic, and endochondral scaffold. This study may have a clinical relevance as a future hypothetical option for allogeneic single-stage cartilage repair and bone regeneration.
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Alves da Silva M, Martins A, Costa-Pinto AR, Monteiro N, Faria S, Reis RL, Neves NM. Electrospun Nanofibrous Meshes Cultured With Wharton's Jelly Stem Cell: An Alternative for Cartilage Regeneration, Without the Need of Growth Factors. Biotechnol J 2017; 12. [PMID: 28902474 DOI: 10.1002/biot.201700073] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Revised: 08/28/2017] [Indexed: 12/24/2022]
Abstract
Many efforts are being directed worldwide to the treatment of OA-focal lesions. The majority of those efforts comprise either the refinement of surgical techniques or combinations of biomaterials with various autologous cells. Herein, we tested electrospun polycaprolactone (PCL) nanofibrous meshes for cartilage tissue engineering. For that, articular chondrocytes (hACs) isolated from human osteoarthritic joints and Wharton's Jelly Stem Cells (hWJSCs) are cultured on electrospun nanofiber meshes, without adding external growth factors. We observed higher glycosaminoglycans production and higher over-expression of cartilage-related genes from hWJSCs cultured with basal medium, when compared to hACs isolated from osteoarthritic joints. Moreover, the presence of sulfated proteoglycans and collagen type II is observed on both types of cell cultures. We believe that this effect is due to either the electrospun nanofibers topography or the intrinsic chondrogenic differentiation potential of hWJSCs. Therefore, we propose the electrospun nanofibrous scaffolds in combination with hWJSCs as a viable alternative to the commercial membranes used in autologous chondrogenic regeneration approaches.
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Affiliation(s)
- Marta Alves da Silva
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, Dept. of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4806-909 Taipas, Guimarães, Portugal
- ICVS/3B's Laboratório Associado PT Government Associate Laboratory, Portugal
| | - Albino Martins
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, Dept. of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4806-909 Taipas, Guimarães, Portugal
- ICVS/3B's Laboratório Associado PT Government Associate Laboratory, Portugal
| | - Ana R Costa-Pinto
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, Dept. of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4806-909 Taipas, Guimarães, Portugal
- ICVS/3B's Laboratório Associado PT Government Associate Laboratory, Portugal
| | - Nélson Monteiro
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, Dept. of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4806-909 Taipas, Guimarães, Portugal
- ICVS/3B's Laboratório Associado PT Government Associate Laboratory, Portugal
| | - Susana Faria
- Prof. S. Faria, Department of Mathematics for Science and Technology, Research CMAT, University of Minho, Guimaraes, Portugal
| | - Rui L Reis
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, Dept. of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4806-909 Taipas, Guimarães, Portugal
- ICVS/3B's Laboratório Associado PT Government Associate Laboratory, Portugal
| | - Nuno M Neves
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, Dept. of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4806-909 Taipas, Guimarães, Portugal
- ICVS/3B's Laboratório Associado PT Government Associate Laboratory, Portugal
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Zhang Y, Guo W, Wang M, Hao C, Lu L, Gao S, Zhang X, Li X, Chen M, Li P, Jiang P, Lu S, Liu S, Guo Q. Co-culture systems-based strategies for articular cartilage tissue engineering. J Cell Physiol 2017; 233:1940-1951. [PMID: 28548713 DOI: 10.1002/jcp.26020] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Accepted: 05/18/2017] [Indexed: 01/01/2023]
Abstract
Cartilage engineering facilitates repair and regeneration of damaged cartilage using engineered tissue that restores the functional properties of the impaired joint. The seed cells used most frequently in tissue engineering, are chondrocytes and mesenchymal stem cells. Seed cells activity plays a key role in the regeneration of functional cartilage tissue. However, seed cells undergo undesirable changes after in vitro processing procedures, such as degeneration of cartilage cells and induced hypertrophy of mesenchymal stem cells, which hinder cartilage tissue engineering. Compared to monoculture, which does not mimic the in vivo cellular environment, co-culture technology provides a more realistic microenvironment in terms of various physical, chemical, and biological factors. Co-culture technology is used in cartilage tissue engineering to overcome obstacles related to the degeneration of seed cells, and shows promise for cartilage regeneration and repair. In this review, we focus first on existing co-culture systems for cartilage tissue engineering and related fields, and discuss the conditions and mechanisms thereof. This is followed by methods for optimizing seed cell co-culture conditions to generate functional neo-cartilage tissue, which will lead to a new era in cartilage tissue engineering.
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Affiliation(s)
- Yu Zhang
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, People's Republic of China
| | - Weimin Guo
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, People's Republic of China
| | - Mingjie Wang
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, People's Republic of China
| | - Chunxiang Hao
- Institute of Anesthesia, Chinese PLA General Hospital, Beijing, People's Republic of China
| | - Liang Lu
- Anhui Provincial Hospital, Hefei, People's Republic of China
| | - Shuang Gao
- Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, People's Republic of China
| | - Xueliang Zhang
- Shanxi Traditional Chinese, Taiyuan, People's Republic of China
| | - Xu Li
- School of Medicine, Naikai University, Tianjin, People's Republic of China
| | - Mingxue Chen
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, People's Republic of China
| | - Penghao Li
- School of Medicine, Naikai University, Tianjin, People's Republic of China
| | - Peng Jiang
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, People's Republic of China
| | - Shibi Lu
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, People's Republic of China
| | - Shuyun Liu
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, People's Republic of China
| | - Quanyi Guo
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, People's Republic of China
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Park YB, Ha CW, Kim JA, Han WJ, Rhim JH, Lee HJ, Kim KJ, Park YG, Chung JY. Single-stage cell-based cartilage repair in a rabbit model: cell tracking and in vivo chondrogenesis of human umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel composite. Osteoarthritis Cartilage 2017; 25:570-580. [PMID: 27789339 DOI: 10.1016/j.joca.2016.10.012] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2016] [Revised: 09/26/2016] [Accepted: 10/15/2016] [Indexed: 02/02/2023]
Abstract
OBJECTIVE Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) have gained popularity as a promising cell source for regenerative medicine, but limited in vivo studies have reported cartilage repair. In addition, the roles of MSCs in cartilage repair are not well-understood. The purpose of this study was to investigate the feasibility of transplanting hUCB-MSCs and hyaluronic acid (HA) hydrogel composite to repair articular cartilage defects in a rabbit model and determine whether the transplanted cells persisted or disappeared from the defect site. DESIGN Osteochondral defects were created in the trochlear grooves of the knees. The hUCB-MSCs and HA composite was transplanted into the defect of experimental knees. Control knees were transplanted by HA or left untreated. Animals were sacrificed at 8 and 16 weeks post-transplantation and additionally at 2 and 4 weeks to evaluate the fate of transplanted cells. The repair tissues were evaluated by gross, histological and immunohistochemical analysis. RESULTS Transplanting hUCB-MSCs and HA composite resulted in overall superior cartilage repair tissue with better quality than HA alone or no treatment. Cellular architecture and collagen arrangement at 16 weeks were similar to those of surrounding normal articular cartilage tissue. Histological scores also revealed that cartilage repair in experimental knees was better than that in control knees. Immunohistochemical analysis with anti-human nuclear antibody confirmed that the transplanted MSCs disappeared gradually over time. CONCLUSION Transplanting hUCB-MSCs and HA composite promote cartilage repair and interactions between hUCB-MSCs and host cells initiated by paracrine action may play an important role in cartilage repair.
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Affiliation(s)
- Y B Park
- Department of Orthopedic Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea.
| | - C W Ha
- Department of Orthopedic Surgery, Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea.
| | - J A Kim
- Department of Orthopedic Surgery, Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
| | - W J Han
- Department of Orthopedic Surgery, Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
| | - J H Rhim
- Department of Orthopedic Surgery, Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
| | - H J Lee
- Department of Orthopedic Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea.
| | - K J Kim
- Department of Orthopedic Surgery, Jeju National University Hospital, Jeju National University School of Medicine, Jeju, South Korea.
| | - Y G Park
- Department of Orthopedic Surgery, Jeju National University Hospital, Jeju National University School of Medicine, Jeju, South Korea.
| | - J Y Chung
- Department of Orthopedic Surgery, Ajou University Hospital, Ajou University School of Medicine, Suwon, South Korea.
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Fong CY, Biswas A, Stunkel W, Chong YS, Bongso A. Tissues Derived From Reprogrammed Wharton's Jelly Stem Cells of the Umbilical Cord Provide an Ideal Platform to Study the Effects of Glucose, Zika Virus, and Other Agents on the Fetus. J Cell Biochem 2016; 118:437-441. [DOI: 10.1002/jcb.25733] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Accepted: 09/09/2016] [Indexed: 12/11/2022]
Affiliation(s)
- Chui-Yee Fong
- Department of Obstetrics and Gynaecology; National University Health System; National University of Singapore; Singapore Singapore
| | - Arijit Biswas
- Department of Obstetrics and Gynaecology; National University Health System; National University of Singapore; Singapore Singapore
| | - Walter Stunkel
- Singapore Institute of Clinical Sciences; Singapore Singapore
| | - Yap-Seng Chong
- Department of Obstetrics and Gynaecology; National University Health System; National University of Singapore; Singapore Singapore
- Singapore Institute of Clinical Sciences; Singapore Singapore
| | - Ariff Bongso
- Department of Obstetrics and Gynaecology; National University Health System; National University of Singapore; Singapore Singapore
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Paduszyński P, Aleksander-Konert E, Zajdel A, Wilczok A, Jelonek K, Witek A, Dzierżewicz Z. Changes in expression of cartilaginous genes during chondrogenesis of Wharton's jelly mesenchymal stem cells on three-dimensional biodegradable poly(L-lactide-co-glycolide) scaffolds. Cell Mol Biol Lett 2016; 21:14. [PMID: 28536617 PMCID: PMC5414664 DOI: 10.1186/s11658-016-0012-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Accepted: 01/08/2016] [Indexed: 01/08/2023] Open
Abstract
Background In cartilage tissue regeneration, it is important to develop biodegradable scaffolds that provide a structural and logistic template for three-dimensional cultures of chondrocytes. In this study, we evaluated changes in expression of cartilaginous genes during in vitro chondrogenic differentiation of WJ-MSCs on PLGA scaffolds. Methods The biocompatibility of the PLGA material was investigated using WJ-MSCs by direct and indirect contact methods according to the ISO 10993–5 standard. PLGA scaffolds were fabricated by the solvent casting/salt-leaching technique. We analyzed expression of chondrogenic genes of WJ-MSCs after a 21-day culture. Results The results showed the biocompatibility of PLGA and confirmed the usefulness of PLGA as material for fabrication of 3D scaffolds that can be applied for WJ-MSC culture. The in vitro penetration and colonization of the scaffolds by WJ-MSCs were assessed by confocal microscopy. The increase in cell number demonstrated that scaffolds made of PLGA copolymers enabled WJ-MSC proliferation. The obtained data showed that as a result of chondrogenesis of WJ-MSCs on the PLGA scaffold the expression of the key markers collagen type II and aggrecan was increased. Conclusions The observed changes in transcriptional activity of cartilaginous genes suggest that the PLGA scaffolds may be applied for WJ-MSC differentiation. This primary study suggests that chondrogenic capacity of WJ-MSCs cultured on the PLGA scaffolds can be useful for cell therapy of cartilage.
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Affiliation(s)
- Piotr Paduszyński
- Department of Biopharmacy, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland
| | - Ewelina Aleksander-Konert
- Department of Biopharmacy, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland
| | - Alicja Zajdel
- Department of Biopharmacy, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland
| | - Adam Wilczok
- Department of Biopharmacy, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland
| | - Katarzyna Jelonek
- Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Zabrze, Poland
| | - Andrzej Witek
- Department of Gynecology and Obstetrics, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | - Zofia Dzierżewicz
- Department of Biopharmacy, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland.,Department of Health Care, Silesian Medical College, Katowice, Poland
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Kalamegam G, Abbas M, Gari M, Alsehli H, Kadam R, Alkaff M, Chaudhary A, Al-Qahtani M, Abuzenadah A, Kafienah W, Mobasheri A. Pelleted Bone Marrow Derived Mesenchymal Stem Cells Are Better Protected from the Deleterious Effects of Arthroscopic Heat Shock. Front Physiol 2016; 7:180. [PMID: 27252654 PMCID: PMC4877393 DOI: 10.3389/fphys.2016.00180] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Accepted: 05/05/2016] [Indexed: 01/10/2023] Open
Abstract
Introduction: The impact of arthroscopic temperature on joint tissues is poorly understood and it is not known how mesenchymal stem cells (MSCs) respond to the effects of heat generated by the device during the process of arthroscopy assisted experimental cell-based therapy. In the present study, we isolated and phenotypically characterized human bone marrow mesenchymal stem cells (hBMMSCs) from osteoarthritis (OA) patients, and evaluated the effect of arthroscopic heat on cells in suspension and pellet cultures. Methods: Primary cultures of hBMMSCs were isolated from bone marrow aspirates of OA patients and cultured using DMEM supplemented with 10% FBS and characterized for their stemness. hBMMSCs (1 × 106 cells) cultured as single cell suspensions or cell pellets were exposed to an illuminated arthroscope for 10, 20, or 30 min. This was followed by analysis of cellular proliferation and heat shock related gene expression. Results: hBMMSCs were viable and exhibited population doubling, short spindle morphology, MSC related CD surface markers expression and tri-lineage differentiation into adipocytes, chondrocytes and osteoblasts. Chondrogenic and osteogenic differentiation increased collagen production and alkaline phosphatase activity. Exposure of hBMMSCs to an illuminated arthroscope for 10, 20, or 30 min for 72 h decreased metabolic activity of the cells in suspensions (63.27% at 30 min) and increased metabolic activity in cell pellets (62.86% at 10 min and 68.57% at 20 min). hBMMSCs exposed to 37, 45, and 55°C for 120 s demonstrated significant upregulation of BAX, P53, Cyclin A2, Cyclin E1, TNF-α, and HSP70 in cell suspensions compared to cell pellets. Conclusions: hBMMSC cell pellets are better protected from temperature alterations compared to cell suspensions. Transplantation of hBMMSCs as pellets rather than as cell suspensions to the cartilage defect site would therefore support their viability and may aid enhanced cartilage regeneration.
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Affiliation(s)
- Gauthaman Kalamegam
- Center of Excellence in Genomic Medicine Research, King Abdulaziz UniversityJeddah, Saudi Arabia; Sheik Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis by Stem Cells, King Abdulaziz UniversityJeddah, Saudi Arabia
| | - Mohammed Abbas
- Sheik Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis by Stem Cells, King Abdulaziz UniversityJeddah, Saudi Arabia; Department of Orthopedic Surgery, Faculty of Medicine, King Abdulaziz University HospitalJeddah, Saudi Arabia
| | - Mamdooh Gari
- Center of Excellence in Genomic Medicine Research, King Abdulaziz UniversityJeddah, Saudi Arabia; Sheik Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis by Stem Cells, King Abdulaziz UniversityJeddah, Saudi Arabia; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz UniversityJeddah, Saudi Arabia
| | - Haneen Alsehli
- Faculty of Applied Medical Sciences, Center of Innovation in Personalized Medicine, King Abdulaziz University Jeddah, Saudi Arabia
| | - Roaa Kadam
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University Jeddah, Saudi Arabia
| | - Mohammed Alkaff
- Sheik Salem Bin Mahfouz Scientific Chair for Treatment of Osteoarthritis by Stem Cells, King Abdulaziz UniversityJeddah, Saudi Arabia; Department of Orthopedic Surgery, Faculty of Medicine, King Abdulaziz University HospitalJeddah, Saudi Arabia
| | - Adeel Chaudhary
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University Jeddah, Saudi Arabia
| | - Mohammed Al-Qahtani
- Center of Excellence in Genomic Medicine Research, King Abdulaziz University Jeddah, Saudi Arabia
| | - Adel Abuzenadah
- Center of Excellence in Genomic Medicine Research, King Abdulaziz UniversityJeddah, Saudi Arabia; Faculty of Applied Medical Sciences, Center of Innovation in Personalized Medicine, King Abdulaziz UniversityJeddah, Saudi Arabia
| | - Wael Kafienah
- School of Cellular and Molecular Medicine, University of Bristol Bristol, UK
| | - Ali Mobasheri
- Center of Excellence in Genomic Medicine Research, King Abdulaziz UniversityJeddah, Saudi Arabia; The D-BOARD European Consortium for Biomarker Discovery, The APPROACH Innovative Medicines Initiative Consortium, Faculty of Health and Medical Sciences, University of SurreySurrey, UK; Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, Arthritis Research UK Pain Centre, Medical Research Council and Arthritis Research UK Centre for Musculoskeletal Aging Research, University of Nottingham, Queen's Medical CentreNottingham, UK
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Chang YH, Liu HW, Wu KC, Ding DC. Mesenchymal Stem Cells and Their Clinical Applications in Osteoarthritis. Cell Transplant 2016; 25:937-50. [DOI: 10.3727/096368915x690288] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Osteoarthritis is a chronic degenerative joint disorder characterized by articular cartilage destruction and osteophyte formation. Chondrocytes in the matrix have a relatively slow turnover rate, and the tissue itself lacks a blood supply to support repair and remodeling. Researchers have evaluated the effectiveness of stem cell therapy and tissue engineering for treating osteoarthritis. All sources of stem cells, including embryonic, induced pluripotent, fetal, and adult stem cells, have potential use in stem cell therapy, which provides a permanent biological solution. Mesenchymal stem cells (MSCs) isolated from bone marrow, adipose tissue, and umbilical cord show considerable promise for use in cartilage repair. MSCs can be sourced from any or all joint tissues and can modulate the immune response. Additionally, MSCs can directly differentiate into chondrocytes under appropriate signal transduction. They also have immunosuppressive and anti-inflammatory paracrine effects. This article reviews the current clinical applications of MSCs and future directions of research in osteoarthritis.
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Affiliation(s)
- Yu-Hsun Chang
- Department of Pediatrics, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
- Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
| | - Hwan-Wun Liu
- Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
- Department of Occupational Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
| | - Kun-Chi Wu
- Department of Orthopedics, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
| | - Dah-Ching Ding
- Department of Pediatrics, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
- Department of Obstetrics and Gynecology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
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42
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Zhao L, Feng Y, Chen X, Yuan J, Liu X, Chen Y, Zhao Y, Liu P, Li Y. Effects of IGF-1 on neural differentiation of human umbilical cord derived mesenchymal stem cells. Life Sci 2016; 151:93-101. [DOI: 10.1016/j.lfs.2016.03.001] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2015] [Revised: 02/28/2016] [Accepted: 03/01/2016] [Indexed: 12/12/2022]
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Khodabandeh Z, Vojdani Z, Talaei-Khozani T, Jaberipour M, Hosseini A, Bahmanpour S. Comparison of the Expression of Hepatic Genes by Human Wharton's Jelly Mesenchymal Stem Cells Cultured in 2D and 3D Collagen Culture Systems. IRANIAN JOURNAL OF MEDICAL SCIENCES 2016; 41:28-36. [PMID: 26722142 PMCID: PMC4691267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
BACKGROUND Human Wharton's jelly mesenchymal stem cells (HWJMSCs) express liver-specific markers such as albumin, alpha-fetoprotein, cytokeratin-19, cytokeratin-18, and glucose-6-phosphatase. Therefore, they can be considered as a good source for cell replacement therapy for liver diseases. This study aimed to evaluate the effects of various culture systems on the hepatocyte-specific gene expression pattern of naïve HWJMSCs. METHODS HWJMSCs were characterized as MSCs by detecting the surface CD markers and capability to differentiate toward osteoblast and adipocyte. HWJMSCs were cultured in 2D collagen films and 3D collagen scaffolds for 21 days and were compared to control cultures. Real time RT-PCR was used to evaluate the expression of liver-specific genes. RESULTS The HWJMSCs which were grown on non-coated culture plates expressed cytokeratin-18 and -19, alpha-fetoprotein, albumin, glucose-6-phosphatase, and claudin. The expression of the hepatic nuclear factor 4 (HNF4) was very low. The cells showed a significant increase in caludin expression when they cultured in 3D collagen scaffolds compared to the conventional monolayer culture and 2D collagen scaffold. CONCLUSION Various culture systems did not influence on hepatocyte specific marker expression by HWJMSCs, except for claudin. The expression of claudin showed that 3D collagen scaffold provided the extracellular matrix for induction of the cells to interconnect with each other.
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Affiliation(s)
- Zahra Khodabandeh
- Laboratory for Stem Cell Research, Department of Anatomy, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran,Transgenic Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Vojdani
- Laboratory for Stem Cell Research, Department of Anatomy, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran,Correspondence: Zahra Vojdani, PhD; Department of Anatomy, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Tel: +98 71 32304372 Fax: +98 71 32304372
| | - Tahereh Talaei-Khozani
- Laboratory for Stem Cell Research, Department of Anatomy, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran,Tissue Engineering Lab, Department of Tissue Engineering, School of Advance Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mansoureh Jaberipour
- Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ahmad Hosseini
- Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Soghra Bahmanpour
- Laboratory for Stem Cell Research, Department of Anatomy, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
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Abstract
Among the surgical options for large full-thickness chondral injuries, cell-based therapy has been practiced and its satisfactory outcomes have been reported. One area that appears promising is cell-based therapies utilizing stem cells. Various tissues within the human body contain mesenchymal stem cells (MSCs) from where these can be harvested. These include bone marrow, adipose, synovium, peripheral blood, and umbilical cord. In this article, both preclinical animal studies and clinical studies dealing with the use of MSCs for cartilage repair of the knee are reviewed. Majority of the clinical papers have shown promising results; however, there are a limited number of studies of high evidence level. Clinical significance of the stem cell therapy as compared to other surgical options as well as optimization of the procedure in terms of cell type and delivery method is still to be determined.
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Affiliation(s)
- Shinichi Yoshiya
- Department of Orthopaedic Surgery, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
| | - Aman Dhawan
- Sports Medicine, Penn State Hershey Bone and Joint Institute, Hershey, PA, 17033-0850, USA.
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Su Y, Cheng R, Zhang J, Qian J, Diao C, Ran J, Zhang H, Li L. Interferon-α2b gene-modified human bone marrow mesenchymal stem cells inhibit hepatocellular carcinoma by reducing the Notch1 levels. Life Sci 2015; 143:18-26. [PMID: 26518164 DOI: 10.1016/j.lfs.2015.10.031] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 10/19/2015] [Accepted: 10/22/2015] [Indexed: 12/12/2022]
Abstract
AIMS Hepatocellular carcinoma (HCC) is the most common liver cancer worldwide. IFN-α has been used in clinics as a potential therapeutic strategy to treat HCC. In spite of the therapeutic effects, IFN-α caused many side effects due to its short half-life and high dose. Here, we aim to detect the anti-tumor effect of a novel gene delivery system - IFN-α2b gene-modified human bone marrow mesenchymal stem cells (BMSCs) in HCC. MAIN METHODS Two HCC cell lines, HepG2 and Huh7 were used in the current study. The secretion of IFN-α2b in the BMSC cultured conditioned media (CM) was measured by ELISA. The cell cycle was determined by flow cytometry. The Xenografted NOD/SCID mouse tumor model was generated by subcutaneous inoculation with HepG2 cells. KEY FINDINGS We found that the IFN-α2b-modified BMSC (BMSC/IFN-α2b) could express IFN-α2b stably. The CM from BMSC/IFN-α2b inhibited the proliferation of HCC cells with a much lower growth rate compared with BMSC/vector-CM or DMEM culture group. We further demonstrated that the population of G2/M phase was higher in BMSC/IFN-α2b-CM treated cells than the other two groups. In addition, BMSC/IFN-α2b could significantly inhibit tumor growth in NOD/SCID mice. Moreover, we found that BMSC/IFN-α2b-CM could significantly decrease the mRNA and protein levels of Notch signaling molecules of HCC in vitro and in vivo. SIGNIFICANCE Our data demonstrated that BMSC/IFN-α2b could significantly inhibit HCC cell growth through negatively regulating the Notch signaling, which suggested that IFN-α2b-modified BMSC may be used as an effective therapeutic strategy for hepatomas.
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Affiliation(s)
- Yanjun Su
- Department of general surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China
| | - Ruochuan Cheng
- Department of general surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China
| | - Jianming Zhang
- Department of general surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China
| | - Jun Qian
- Department of general surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China
| | - Chang Diao
- Department of general surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China
| | - Jianghua Ran
- Department of Hepatobiliary Surgery, The Calmette Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650011, China
| | - Hongqing Zhang
- Department of Hepatobiliary Surgery, The Calmette Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650011, China
| | - Li Li
- Department of Hepatobiliary Surgery, The Calmette Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650011, China.
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In vitro differentiation process of human Wharton’s jelly mesenchymal stem cells to male germ cells in the presence of gonadal and non-gonadal conditioned media with retinoic acid. In Vitro Cell Dev Biol Anim 2015; 51:1093-101. [DOI: 10.1007/s11626-015-9929-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2014] [Accepted: 06/08/2015] [Indexed: 01/01/2023]
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Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration. Methods 2015; 99:69-80. [PMID: 26384579 DOI: 10.1016/j.ymeth.2015.09.015] [Citation(s) in RCA: 333] [Impact Index Per Article: 33.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2015] [Revised: 08/10/2015] [Accepted: 09/15/2015] [Indexed: 01/15/2023] Open
Abstract
Musculoskeletal disorders represent a major cause of disability and morbidity globally and result in enormous costs for health and social care systems. Development of cell-based therapies is rapidly proliferating in a number of disease areas, including musculoskeletal disorders. Novel biological therapies that can effectively treat joint and spine degeneration are high priorities in regenerative medicine. Mesenchymal stem cells (MSCs) isolated from bone marrow (BM-MSCs), adipose tissue (AD-MSCs) and umbilical cord (UC-MSCs) show considerable promise for use in cartilage and intervertebral disc (IVD) repair. This review article focuses on stem cell-based therapeutics for cartilage and IVD repair in the context of the rising global burden of musculoskeletal disorders. We discuss the biology MSCs and chondroprogenitor cells and specifically focus on umbilical cord/Wharton's jelly derived MSCs and examine their potential for regenerative applications. We also summarize key components of the molecular machinery and signaling pathways responsible for the control of chondrogenesis and explore biomimetic scaffolds and biomaterials for articular cartilage and IVD regeneration. This review explores the exciting opportunities afforded by MSCs and discusses the challenges associated with cartilage and IVD repair and regeneration. There are still many technical challenges associated with isolating, expanding, differentiating, and pre-conditioning MSCs for subsequent implantation into degenerate joints and the spine. However, the prospect of combining biomaterials and cell-based therapies that incorporate chondrocytes, chondroprogenitors and MSCs leads to the optimistic view that interdisciplinary approaches will lead to significant breakthroughs in regenerating musculoskeletal tissues, such as the joint and the spine in the near future.
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Sypecka J, Sarnowska A. Mesenchymal cells of umbilical cord and umbilical cord blood as a source of human oligodendrocyte progenitors. Life Sci 2015; 139:24-9. [PMID: 26285174 DOI: 10.1016/j.lfs.2015.08.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2015] [Revised: 07/06/2015] [Accepted: 08/11/2015] [Indexed: 12/16/2022]
Affiliation(s)
- Joanna Sypecka
- NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5, Pawinskiego str., 02-106 Warsaw, Poland.
| | - Anna Sarnowska
- Translative Platform for Regenerative Medicine, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego Street, 02-106 Warsaw, Poland; Stem Cell Bioengineering Laboratory, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego Street, 02-106 Warsaw, Poland
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Stem Cells and Regenerative Medicine: Myth or Reality of the 21th Century. Stem Cells Int 2015; 2015:734731. [PMID: 26300923 PMCID: PMC4537770 DOI: 10.1155/2015/734731] [Citation(s) in RCA: 111] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2014] [Revised: 04/22/2015] [Accepted: 05/24/2015] [Indexed: 02/07/2023] Open
Abstract
Since the 1960s and the therapeutic use of hematopoietic stem cells of bone marrow origin, there has been an increasing interest in the study of undifferentiated progenitors that have the ability to proliferate and differentiate into various tissues. Stem cells (SC) with different potency can be isolated and characterised. Despite the promise of embryonic stem cells, in many cases, adult or even fetal stem cells provide a more interesting approach for clinical applications. It is undeniable that mesenchymal stem cells (MSC) from bone marrow, adipose tissue, or Wharton's Jelly are of potential interest for clinical applications in regenerative medicine because they are easily available without ethical problems for their uses. During the last 10 years, these multipotent cells have generated considerable interest and have particularly been shown to escape to allogeneic immune response and be capable of immunomodulatory activity. These properties may be of a great interest for regenerative medicine. Different clinical applications are under study (cardiac insufficiency, atherosclerosis, stroke, bone and cartilage deterioration, diabetes, urology, liver, ophthalmology, and organ's reconstruction). This review focuses mainly on tissue and organ regeneration using SC and in particular MSC.
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Klontzas ME, Kenanidis EI, Heliotis M, Tsiridis E, Mantalaris A. Bone and cartilage regeneration with the use of umbilical cord mesenchymal stem cells. Expert Opin Biol Ther 2015; 15:1541-52. [PMID: 26176327 DOI: 10.1517/14712598.2015.1068755] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
INTRODUCTION The production of functional alternatives to bone autografts and the development new treatment strategies for cartilage defects are great challenges that could be addressed by the field of tissue engineering. Umbilical cord mesenchymal stem cells (MSCs) can be used to produce cost-effective, atraumatic and possibly autologous bone and cartilage grafts. AREAS COVERED MSCs can be isolated from umbilical cord Wharton's jelly, perivascular tissue and blood using various techniques. Those cells have been characterized and phenotypic similarities with bone marrow-derived MSCs (BM-MSCs) and embryonic stem cells have been found. Findings on their differentiation into the osteogenic and chondrogenic lineage differ between studies and are not as consistent as for BM-MSCs. EXPERT OPINION MSCs from umbilical cords have to be more extensively studied and the mechanisms underlying their differentiation have to be clarified. To date, they seem to be an attractive alternative to BM-MSCs. However, further research with suitable scaffolds and growth factors as well as with novel scaffold fabrication and culture technology should be conducted before they are introduced to clinical practice and replace BM-MSCs.
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Affiliation(s)
- Michail E Klontzas
- a 1 Imperial College London, Department of Chemical Engineering and Chemical Technology , South Kensington Campus, London, UK
| | - Eustathios I Kenanidis
- b 2 Aristotle University Medical School, Academic Orthopaedic Unit , University Campus 54 124, Thessaloniki, Greece.,c 3 Aristotle University Medical School, "PapaGeorgiou" General Hospital, Academic Orthopaedic Unit , Thessaloniki, Greece
| | | | - Eleftherios Tsiridis
- b 2 Aristotle University Medical School, Academic Orthopaedic Unit , University Campus 54 124, Thessaloniki, Greece.,e 5 Imperial College London, Department of Surgery and Cancer, Division of Surgery , B-block, Hammersmith, Du-Cane Road, London, UK
| | - Athanasios Mantalaris
- f 6 Imperial College London, Department of Chemical Engineering , South Kensington Campus, London, UK
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