|
1
|
Gu C, Tang Q, Li L, Chen Y. Optimization and Implication of Adipose-Derived Stem Cells in Craniofacial Bone Regeneration and Repair. Bioengineering (Basel) 2024; 11:1100. [PMID: 39593759 PMCID: PMC11592193 DOI: 10.3390/bioengineering11111100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Revised: 10/17/2024] [Accepted: 10/27/2024] [Indexed: 11/28/2024] Open
Abstract
Adipose-derived stem cells (ADSCs) have emerged as a promising resource for craniofacial bone regeneration due to their high abundance and easy accessibility, significant osteogenic potential, versatile applications, and potential for personalized medicine, which underscore their importance in this field. This article reviews the current progress of preclinical studies that describe the careful selection of specific ADSC subpopulations, key signaling pathways involved, and usage of various strategies to enhance the osteogenic potential of ADSCs. Additionally, clinical case reports regarding the application of ADSCs in the repair of calvarial defects, cranio-maxillofacial defects, and alveolar bone defects are also discussed.
Collapse
Affiliation(s)
- Cong Gu
- Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA; (Q.T.); (L.L.); (Y.C.)
| | - Qinghuang Tang
- Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA; (Q.T.); (L.L.); (Y.C.)
- Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY 14214, USA
| | - Liwen Li
- Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA; (Q.T.); (L.L.); (Y.C.)
- Department of Biological Sciences, University at Buffalo, Buffalo, NY 14260, USA
| | - YiPing Chen
- Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA; (Q.T.); (L.L.); (Y.C.)
| |
Collapse
|
|
2
|
Guo Q, Chen J, Bu Q, Zhang J, Ruan M, Chen X, Zhao M, Tu X, Zhao C. Establishing stable and highly osteogenic hiPSC-derived MSCs for 3D-printed bone graft through microenvironment modulation by CHIR99021-treated osteocytes. Mater Today Bio 2024; 26:101111. [PMID: 38933413 PMCID: PMC11201125 DOI: 10.1016/j.mtbio.2024.101111] [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: 02/24/2024] [Revised: 05/17/2024] [Accepted: 05/31/2024] [Indexed: 06/28/2024] Open
Abstract
Human induced pluripotent stem cell (hiPSC)-derived mesenchymal stem cells (iMSCs) are ideal candidates for the production of standardised and scalable bioengineered bone grafts. However, stable induction and osteogenic differentiation of iMSCs pose challenges in the industry. We developed a precise differentiation method to produce homogeneous and fully differentiated iMSCs. In this study, we established a standardised system to prepare iMSCs with increased osteogenic potential and improved bioactivity by introducing a CHIR99021 (C91)-treated osteogenic microenvironment (COOME). COOME enhances the osteogenic differentiation and mineralisation of iMSCs via canonical Wnt signalling. Global transcriptome analysis and co-culturing experiments indicated that COOME increased the pro-angiogenesis/neurogenesis activity of iMSCs. The superior osteogenic differentiation and mineralisation abilities of COOME-treated iMSCs were also confirmed in a Bio3D module generated using a polycaprolactone (PCL) and cell-integrated 3D printing (PCI3D) system, which is the closest model to in vivo research. This COOME-treated iMSCs differentiation system offers a new perspective for generating highly osteogenic, bioactive, and anatomically matched grafts for clinical applications. Statement of significance Although human induced pluripotent stem cell-derived MSCs (iMSCs) are ideal seed cells for synthetic bone implants, the challenges of stable induction and osteogenic differentiation hinder their clinical application. This study established a standardised system for the scalable preparation of iMSCs with improved osteogenic potential by combining our precise iMSC differentiation method with the CHIR99021 (C91)-treated osteocyte osteogenic microenvironment (COOME) through the activation of canonical Wnt signalling. Moreover, COOME upregulated the pro-angiogenic and pro-neurogenic capacities of iMSCs, which are crucial for the integration of implanted bone grafts. The superior osteogenic ability of COOME-treated iMSCs was confirmed in Bio3D modules generated using PCL and cell-integrated 3D printing systems, highlighting their functional potential in vivo. This study contributes to tissue engineering by providing insights into the functional differentiation of iMSCs for bone regeneration.
Collapse
Affiliation(s)
- Qiuling Guo
- Laboratory of Skeletal Development and Regeneration, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Jingjing Chen
- Laboratory of Skeletal Development and Regeneration, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Qiqi Bu
- Laboratory of Skeletal Development and Regeneration, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Jinling Zhang
- Laboratory of Skeletal Development and Regeneration, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Minjie Ruan
- Laboratory of Skeletal Development and Regeneration, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Xiaoyu Chen
- Center for Medical Epigenetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China
| | - Mingming Zhao
- Center for Medical Epigenetics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China
| | - Xiaolin Tu
- Laboratory of Skeletal Development and Regeneration, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Chengzhu Zhao
- Laboratory of Skeletal Development and Regeneration, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China
| |
Collapse
|
|
3
|
Zheng Z, Liu H, Liu S, Luo E, Liu X. Mesenchymal stem cells in craniofacial reconstruction: a comprehensive review. Front Mol Biosci 2024; 11:1362338. [PMID: 38690295 PMCID: PMC11058977 DOI: 10.3389/fmolb.2024.1362338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 03/29/2024] [Indexed: 05/02/2024] Open
Abstract
Craniofacial reconstruction faces many challenges, including high complexity, strong specificity, severe injury, irregular and complex wounds, and high risk of bleeding. Traditionally, the "gold standard" for treating craniofacial bone defects has been tissue transplantation, which involves the transplantation of bone, cartilage, skin, and other tissues from other parts of the body. However, the shape of craniofacial bone and cartilage structures varies greatly and is distinctly different from ordinary long bones. Craniofacial bones originate from the neural crest, while long bones originate from the mesoderm. These factors contribute to the poor effectiveness of tissue transplantation in repairing craniofacial defects. Autologous mesenchymal stem cell transplantation exhibits excellent pluripotency, low immunogenicity, and minimally invasive properties, and is considered a potential alternative to tissue transplantation for treating craniofacial defects. Researchers have found that both craniofacial-specific mesenchymal stem cells and mesenchymal stem cells from other parts of the body have significant effects on the restoration and reconstruction of craniofacial bones, cartilage, wounds, and adipose tissue. In addition, the continuous development and application of tissue engineering technology provide new ideas for craniofacial repair. With the continuous exploration of mesenchymal stem cells by researchers and the continuous development of tissue engineering technology, the use of autologous mesenchymal stem cell transplantation for craniofacial reconstruction has gradually been accepted and promoted. This article will review the applications of various types of mesenchymal stem cells and related tissue engineering in craniofacial repair and reconstruction.
Collapse
Affiliation(s)
| | | | | | - En Luo
- State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Xian Liu
- State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| |
Collapse
|
|
4
|
Dhanjal DS, Singh R, Sharma V, Nepovimova E, Adam V, Kuca K, Chopra C. Advances in Genetic Reprogramming: Prospects from Developmental Biology to Regenerative Medicine. Curr Med Chem 2024; 31:1646-1690. [PMID: 37138422 DOI: 10.2174/0929867330666230503144619] [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: 11/12/2022] [Revised: 03/13/2023] [Accepted: 03/16/2023] [Indexed: 05/05/2023]
Abstract
The foundations of cell reprogramming were laid by Yamanaka and co-workers, who showed that somatic cells can be reprogrammed into pluripotent cells (induced pluripotency). Since this discovery, the field of regenerative medicine has seen advancements. For example, because they can differentiate into multiple cell types, pluripotent stem cells are considered vital components in regenerative medicine aimed at the functional restoration of damaged tissue. Despite years of research, both replacement and restoration of failed organs/ tissues have remained elusive scientific feats. However, with the inception of cell engineering and nuclear reprogramming, useful solutions have been identified to counter the need for compatible and sustainable organs. By combining the science underlying genetic engineering and nuclear reprogramming with regenerative medicine, scientists have engineered cells to make gene and stem cell therapies applicable and effective. These approaches have enabled the targeting of various pathways to reprogramme cells, i.e., make them behave in beneficial ways in a patient-specific manner. Technological advancements have clearly supported the concept and realization of regenerative medicine. Genetic engineering is used for tissue engineering and nuclear reprogramming and has led to advances in regenerative medicine. Targeted therapies and replacement of traumatized , damaged, or aged organs can be realized through genetic engineering. Furthermore, the success of these therapies has been validated through thousands of clinical trials. Scientists are currently evaluating induced tissue-specific stem cells (iTSCs), which may lead to tumour-free applications of pluripotency induction. In this review, we present state-of-the-art genetic engineering that has been used in regenerative medicine. We also focus on ways that genetic engineering and nuclear reprogramming have transformed regenerative medicine and have become unique therapeutic niches.
Collapse
Affiliation(s)
- Daljeet Singh Dhanjal
- School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, India
| | - Reena Singh
- School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, India
| | - Varun Sharma
- Head of Bioinformatic Division, NMC Genetics India Pvt. Ltd., Gurugram, India
| | - Eugenie Nepovimova
- Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, 50003, Czech Republic
| | - Vojtech Adam
- Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno, CZ 613 00, Czech Republic
- Central European Institute of Technology, Brno University of Technology, Purkynova 123, Brno, CZ-612 00, Czech Republic
| | - Kamil Kuca
- Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, 50003, Czech Republic
- Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, 50005, Czech Republic
| | - Chirag Chopra
- School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, India
| |
Collapse
|
|
5
|
Carballo-Pedrares N, Ponti F, Lopez-Seijas J, Miranda-Balbuena D, Bono N, Candiani G, Rey-Rico A. Non-viral gene delivery to human mesenchymal stem cells: a practical guide towards cell engineering. J Biol Eng 2023; 17:49. [PMID: 37491322 PMCID: PMC10369726 DOI: 10.1186/s13036-023-00363-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 06/27/2023] [Indexed: 07/27/2023] Open
Abstract
In recent decades, human mesenchymal stem cells (hMSCs) have gained momentum in the field of cell therapy for treating cartilage and bone injuries. Despite the tri-lineage multipotency, proliferative properties, and potent immunomodulatory effects of hMSCs, their clinical potential is hindered by donor variations, limiting their use in medical settings. To address this challenge, gene delivery technologies have emerged as a promising approach to modulate the phenotype and commitment of hMSCs towards specific cell lineages, thereby enhancing osteochondral repair strategies. This review provides a comprehensive overview of current non-viral gene delivery approaches used to engineer MSCs, highlighting key factors such as the choice of nucleic acid or delivery vector, transfection strategies, and experimental parameters. Additionally, it outlines various protocols and methods for qualitative and quantitative evaluation of their therapeutic potential as a delivery system in osteochondral regenerative applications. In summary, this technical review offers a practical guide for optimizing non-viral systems in osteochondral regenerative approaches. hMSCs constitute a key target population for gene therapy techniques. Nevertheless, there is a long way to go for their translation into clinical treatments. In this review, we remind the most relevant transfection conditions to be optimized, such as the type of nucleic acid or delivery vector, the transfection strategy, and the experimental parameters to accurately evaluate a delivery system. This survey provides a practical guide to optimizing non-viral systems for osteochondral regenerative approaches.
Collapse
Affiliation(s)
- Natalia Carballo-Pedrares
- Gene & Cell Therapy Research Group (G-CEL). Centro Interdisciplinar de Química y Biología - CICA, Universidade da Coruña, As Carballeiras, S/N. Campus de Elviña, 15071 A, Coruña, Spain
| | - Federica Ponti
- genT_LΛB, Department of Chemistry, Materials and Chemical Engineering "G. Natta", Politecnico Di Milano, 20131, Milan, Italy
- Laboratory for Biomaterials and Bioengineering, Canada Research Chair I in Biomaterials and Bioengineering for the Innovation in Surgery, Department of Min-Met-Materials Engineering & Research Center of CHU de Quebec, Division of Regenerative Medicine, Laval University, Quebec City, QC, Canada
| | - Junquera Lopez-Seijas
- Gene & Cell Therapy Research Group (G-CEL). Centro Interdisciplinar de Química y Biología - CICA, Universidade da Coruña, As Carballeiras, S/N. Campus de Elviña, 15071 A, Coruña, Spain
| | - Diego Miranda-Balbuena
- Gene & Cell Therapy Research Group (G-CEL). Centro Interdisciplinar de Química y Biología - CICA, Universidade da Coruña, As Carballeiras, S/N. Campus de Elviña, 15071 A, Coruña, Spain
| | - Nina Bono
- genT_LΛB, Department of Chemistry, Materials and Chemical Engineering "G. Natta", Politecnico Di Milano, 20131, Milan, Italy
| | - Gabriele Candiani
- genT_LΛB, Department of Chemistry, Materials and Chemical Engineering "G. Natta", Politecnico Di Milano, 20131, Milan, Italy.
| | - Ana Rey-Rico
- Gene & Cell Therapy Research Group (G-CEL). Centro Interdisciplinar de Química y Biología - CICA, Universidade da Coruña, As Carballeiras, S/N. Campus de Elviña, 15071 A, Coruña, Spain.
| |
Collapse
|
|
6
|
Romano IR, D’Angeli F, Vicario N, Russo C, Genovese C, Lo Furno D, Mannino G, Tamburino S, Parenti R, Giuffrida R. Adipose-Derived Mesenchymal Stromal Cells: A Tool for Bone and Cartilage Repair. Biomedicines 2023; 11:1781. [PMID: 37509421 PMCID: PMC10376676 DOI: 10.3390/biomedicines11071781] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 06/16/2023] [Accepted: 06/20/2023] [Indexed: 07/30/2023] Open
Abstract
The osteogenic and chondrogenic differentiation ability of adipose-derived mesenchymal stromal cells (ASCs) and their potential therapeutic applications in bone and cartilage defects are reported in this review. This becomes particularly important when these disorders can only be poorly treated by conventional therapeutic approaches, and tissue engineering may represent a valuable alternative. Being of mesodermal origin, ASCs can be easily induced to differentiate into chondrocyte-like and osteocyte-like elements and used to repair damaged tissues. Moreover, they can be easily harvested and used for autologous implantation. A plethora of ASC-based strategies are being developed worldwide: they include the transplantation of freshly harvested cells, in vitro expanded cells or predifferentiated cells. Moreover, improving their positive effects, ASCs can be implanted in combination with several types of scaffolds that ensure the correct cell positioning; support cell viability, proliferation and migration; and may contribute to their osteogenic or chondrogenic differentiation. Examples of these strategies are described here, showing the enormous therapeutic potential of ASCs in this field. For safety and regulatory issues, most investigations are still at the experimental stage and carried out in vitro and in animal models. Clinical applications have, however, been reported with promising results and no serious adverse effects.
Collapse
Affiliation(s)
- Ivana Roberta Romano
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (I.R.R.); (N.V.); (C.R.); (R.P.); (R.G.)
| | - Floriana D’Angeli
- Department of Human Sciences and Quality of Life Promotion, San Raffaele Roma Open University, 00166 Rome, Italy;
| | - Nunzio Vicario
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (I.R.R.); (N.V.); (C.R.); (R.P.); (R.G.)
| | - Cristina Russo
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (I.R.R.); (N.V.); (C.R.); (R.P.); (R.G.)
| | - Carlo Genovese
- Faculty of Medicine and Surgery, “Kore” University of Enna, 94100 Enna, Italy;
| | - Debora Lo Furno
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (I.R.R.); (N.V.); (C.R.); (R.P.); (R.G.)
| | - Giuliana Mannino
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, Italy
| | - Serena Tamburino
- Chi.Pla Chirurgia Plastica, Via Suor Maria Mazzarello, 54, 95128 Catania, Italy;
| | - Rosalba Parenti
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (I.R.R.); (N.V.); (C.R.); (R.P.); (R.G.)
| | - Rosario Giuffrida
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (I.R.R.); (N.V.); (C.R.); (R.P.); (R.G.)
| |
Collapse
|
|
7
|
Du L, Qin C, Zhang H, Han F, Xue J, Wang Y, Wu J, Xiao Y, Huan Z, Wu C. Multicellular Bioprinting of Biomimetic Inks for Tendon-to-Bone Regeneration. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023:e2301309. [PMID: 37119499 PMCID: PMC10375072 DOI: 10.1002/advs.202301309] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Indexed: 06/19/2023]
Abstract
Tendon-to-bone interface has a hierarchical structure and gradient component that are conducive to distributing the stresses to achieve movement. Conventional biomaterials lack the capacity to induce synchronous repair of multiple tissues, resulting in the failure of the interface repair. Biomimetic strategies have attracted enormous attention in the field of complex structure regeneration because they can meet the different physiological requirements of multiple tissues. Herein, a biomimetic ink mimicking tendon/bone tissues is developed by combining tendon/bone-related cells and Mo-containing silicate (MS) bioceramics. Subsequently, biomimetic multicellular scaffolds are fabricated to achieve the simulation of the hierarchical structure and cellular composition of tendon-to-bone interfaces by the spatial distribution of the biomimetic inks via 3D bioprinting, which is of great significance for inducing the regeneration of complex structures in the interface region. In addition, attributed to the desirable ionic microenvironment created by MS bioceramics, the biomimetic scaffolds possess the dual function of inducing tendon/bone-related cells tenogenic and osteogenic differentiation in vitro, and promote the integrated regeneration of tendon-to-bone interfaces in vivo. The study offers a feasible strategy to construct biomimetic multicellular scaffolds with bifunction for inducing multi-lineage tissue regeneration, especially for regenerating soft-to-hard tissue interfaces.
Collapse
Affiliation(s)
- Lin Du
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai, 200050, P. R. China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing, 100049, P. R. China
| | - Chen Qin
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai, 200050, P. R. China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing, 100049, P. R. China
| | - Hongjian Zhang
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai, 200050, P. R. China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing, 100049, P. R. China
| | - Fei Han
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai, 200050, P. R. China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing, 100049, P. R. China
| | - Jianmin Xue
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai, 200050, P. R. China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing, 100049, P. R. China
| | - Yufeng Wang
- Nanjing First Hospital, Nanjing Medical University, 68th Changle Road, Nanjing, Jiangsu, 210006, P. R. China
| | - Jinfu Wu
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai, 200050, P. R. China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing, 100049, P. R. China
| | - Yin Xiao
- School of Medicine and Dentistry, Menzies Health Institute Queensland, Griffith University, Queensland, 4222, Australia
| | - Zhiguang Huan
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai, 200050, P. R. China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing, 100049, P. R. China
| | - Chengtie Wu
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai, 200050, P. R. China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing, 100049, P. R. China
| |
Collapse
|
|
8
|
Hosseinkhani H, Domb AJ, Sharifzadeh G, Nahum V. Gene Therapy for Regenerative Medicine. Pharmaceutics 2023; 15:856. [PMID: 36986717 PMCID: PMC10057434 DOI: 10.3390/pharmaceutics15030856] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 02/24/2023] [Accepted: 03/01/2023] [Indexed: 03/08/2023] Open
Abstract
The development of biological methods over the past decade has stimulated great interest in the possibility to regenerate human tissues. Advances in stem cell research, gene therapy, and tissue engineering have accelerated the technology in tissue and organ regeneration. However, despite significant progress in this area, there are still several technical issues that must be addressed, especially in the clinical use of gene therapy. The aims of gene therapy include utilising cells to produce a suitable protein, silencing over-producing proteins, and genetically modifying and repairing cell functions that may affect disease conditions. While most current gene therapy clinical trials are based on cell- and viral-mediated approaches, non-viral gene transfection agents are emerging as potentially safe and effective in the treatment of a wide variety of genetic and acquired diseases. Gene therapy based on viral vectors may induce pathogenicity and immunogenicity. Therefore, significant efforts are being invested in non-viral vectors to enhance their efficiency to a level comparable to the viral vector. Non-viral technologies consist of plasmid-based expression systems containing a gene encoding, a therapeutic protein, and synthetic gene delivery systems. One possible approach to enhance non-viral vector ability or to be an alternative to viral vectors would be to use tissue engineering technology for regenerative medicine therapy. This review provides a critical view of gene therapy with a major focus on the development of regenerative medicine technologies to control the in vivo location and function of administered genes.
Collapse
Affiliation(s)
- Hossein Hosseinkhani
- Innovation Center for Advanced Technology, Matrix, Inc., New York, NY 10019, USA
| | - Abraham J. Domb
- The Center for Nanoscience and Nanotechnology, Alex Grass Center for Drug Design and Synthesis and Cannabinoids Research, School of Pharmacy, Faculty of Medicine, Institute of Drug Research, The Hebrew University of Jerusalem, Jerusalem 91120, Israel
| | - Ghorbanali Sharifzadeh
- Department of Polymer Engineering, School of Chemical Engineering, Universiti Teknologi Malaysia, Skudai 81310, Johor, Malaysia
| | - Victoria Nahum
- The Center for Nanoscience and Nanotechnology, Alex Grass Center for Drug Design and Synthesis and Cannabinoids Research, School of Pharmacy, Faculty of Medicine, Institute of Drug Research, The Hebrew University of Jerusalem, Jerusalem 91120, Israel
| |
Collapse
|
|
9
|
Cai F, Yusufu A, Liu K, Chen W, Zhao R, Liu Y, Liu Y. High-fat diet causes undesirable bone regeneration by altering the bone marrow environment in rats. Front Endocrinol (Lausanne) 2023; 14:1088508. [PMID: 37056669 PMCID: PMC10086432 DOI: 10.3389/fendo.2023.1088508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Accepted: 03/14/2023] [Indexed: 03/30/2023] Open
Abstract
OBJECTIVE Diet structure has changed greatly over the last few decades, and high-calorie diets have become an integral part of people's daily diet, as well as the important cause of obesity in society. Several organ systems, including the skeletal system, are seriously affected by high-fat-diets (HFD) in the world. There is, however, still a lack of knowledge about the effects of HFD on bone regeneration and the possible mechanisms involved. In this study, the difference in bone regeneration between rats under HFD and low-fat-diets (LFD) was evaluated by monitoring the process of bone regeneration in distraction osteogenesis (DO) model animals, as well as the possible mechanisms. METHODS A total of 40 Sprague Dawley (SD) rats (5 weeks old) were randomly divided into HFD group (n=20) and LFD group (n=20). Except for feeding methods, there were no differences between the two groups in terms of treatment conditions. All animals received the DO surgery eight weeks after starting to feed. After a delay of 5 days (latency phase), the active lengthening phase was performed for 10 days (0.25 mm/12 h), and the consolidation phase followed for 42 days. An observational study of bone included radioscopy (once a week), micro-computed tomography (CT), general morphology, biomechanics, histomorphometry, and immunohistochemistry. RESULT The results showed that HFD group had a higher body weight than LFD group after 8, 14, and 16 weeks of feeding. Furthermore, at the final observation, there were statistically significant differences between LFD group and HFD group in terms of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels. Additionally, observations on bone regeneration showed a slower regeneration and a lower biomechanical strength in HFD group than LFD group, based on radiography, micro-CT, general morphology, biomechanics, histomorphometry, and immunohistochemistry. CONCLUSION In this study, HFD resulted in elevated blood lipids, increased adipose differentiation at the bone marrow level, and delayed bone regeneration. The pieces of evidence are beneficial to better understand the association between diet and bone regeneration and to adjust the diet optimally for fracture patients.
Collapse
Affiliation(s)
- Feiyu Cai
- Department of Burns and Plastic Surgery & Wound Repair Surgery, The Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Aihemaitijiang Yusufu
- Department of Trauma and Micro Reconstructive Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Kai Liu
- Department of Trauma and Micro Reconstructive Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Wenjiao Chen
- Department of Burns and Plastic Surgery & Wound Repair Surgery, The Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Ruomei Zhao
- Department of Burns and Plastic Surgery & Wound Repair Surgery, The Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Yanshi Liu
- Department of Orthopaedics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
- *Correspondence: Yi Liu, ; Yanshi Liu,
| | - Yi Liu
- Department of Burns and Plastic Surgery & Wound Repair Surgery, The Lanzhou University Second Hospital, Lanzhou, Gansu, China
- *Correspondence: Yi Liu, ; Yanshi Liu,
| |
Collapse
|
|
10
|
Cui J, Yu X, Yu B, Yang X, Fu Z, Wan J, Zhu M, Wang X, Lin K. Coaxially Fabricated Dual-Drug Loading Electrospinning Fibrous Mat with Programmed Releasing Behavior to Boost Vascularized Bone Regeneration. Adv Healthc Mater 2022; 11:e2200571. [PMID: 35668705 DOI: 10.1002/adhm.202200571] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 05/22/2022] [Indexed: 01/24/2023]
Abstract
In clinical treatment, the bone regeneration of critical-size defects is desiderated to be solved, and the regeneration of large bone segment defects depends on early vascularization. Therefore, overcoming insufficient vascularization in artificial bone grafts may be a promising strategy for critical-size bone regeneration. Herein, a novel dual-drug programmed releasing electrospinning fibrous mat (EFM) with a deferoxamine (DFO)-loaded shell layer and a dexamethasone (DEX)-loaded core layer is fabricated using coaxial electrospinning technology, considering the temporal sequence of vascularization and bone repair. DFO acts as an angiogenesis promoter and DEX is used as an osteogenesis inducer. The results demonstrate that the early and rapid release of DFO promotes angiogenesis in human umbilical vascular endothelial cells and the sustained release of DEX enhances the osteogenic differentiation of rat bone mesenchymal stem cells. DFO and DEX exert synergetic effects on osteogenic differentiation via the Wnt/β-catenin signaling pathway, and the dual-drug programmed releasing EFM acquired perfect vascularized bone regeneration ability in a rat calvarial defect model. Overall, the study suggests a low-cost strategy to enhance vascularized bone regeneration by adjusting the behavior of angiogenesis and osteogenesis in time dimension.
Collapse
Affiliation(s)
- Jinjie Cui
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, 200011, China
| | - Xingge Yu
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, 200011, China
| | - Bin Yu
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, 200011, China
| | - Xiuyi Yang
- Department of Orthodontics, Affiliated Stomatological Hospital of Soochow University, Suzhou, 215005, China
| | - Zeyu Fu
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, 200011, China
| | - Jianyu Wan
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, 200011, China
| | - Min Zhu
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, 200011, China
| | - Xudong Wang
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, 200011, China
| | - Kaili Lin
- Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Research Unit of Oral and Maxillofacial Regenerative Medicine, Chinese Academy of Medical Sciences, Shanghai, 200011, China
| |
Collapse
|
|
11
|
Zhao Y, Xing Y, Wang M, Huang Y, Xu H, Su Y, Zhao Y, Shang Y. Supramolecular Hydrogel Based on an Osteogenic Growth Peptide Promotes Bone Defect Repair. ACS OMEGA 2022; 7:11395-11404. [PMID: 35415354 PMCID: PMC8992256 DOI: 10.1021/acsomega.2c00501] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 03/16/2022] [Indexed: 05/13/2023]
Abstract
Current bone defect treatment strategies are associated with several risks and have major limitations. Therefore, it is necessary to develop an inexpensive growth factor delivery system that can be easily produced in large quantities and can promote long-term bone regeneration. An osteogenic growth peptide (OGP) is a 14 amino acid peptide with a short peptide sequence active fragment. In this study, we developed two OGP-based self-assembling supramolecular hydrogels (F- and G-sequence hydrogels) and investigated the in vitro and in vivo effects on proliferation and osteogenesis, including the mechanism of hydrogel-mediated bone defect repair. The hydrogels presented excellent biocompatibility and cell proliferation-promoting properties (1.5-1.7-fold increase). The hydrogels could effectively upregulate the expression of osteogenic factors, including RUNX2, BMP2, OCN, and OPN, to promote osteogenesis differentiation. Interestingly, 353 differentially expressed genes were identified in hBMSCs treated with hydrogels. The hydrogels were proved to be involved in the inflammatory pathways and folate-related pathways to mediate the osteogenesis differentiation. Furthermore, the therapeutic efficiency (bone volume/total volume, trabecular number, and bone mineral density) of hydrogels on bone regeneration in vivo was evaluated. The results showed that the hydrogels promoted bone formation in the early stage of bone defect healing. Taken together, this study was the first to develop and evaluate the properties of OGP-based self-assembling supramolecular hydrogels. Our study will provide inspiration for the development of delivering OGP for bone regeneration.
Collapse
Affiliation(s)
- Yanhong Zhao
- Hospital
of Stomatology, Tianjin Medical University, Tianjin 300070, People ’s Republic of China
| | - Yi Xing
- Hospital
of Stomatology, Tianjin Medical University, Tianjin 300070, People ’s Republic of China
| | - Min Wang
- Hospital
of Stomatology, Tianjin Medical University, Tianjin 300070, People ’s Republic of China
| | - Ying Huang
- Hospital
of Stomatology, Tianjin Medical University, Tianjin 300070, People ’s Republic of China
| | - Hainan Xu
- Hospital
of Stomatology, Tianjin Medical University, Tianjin 300070, People ’s Republic of China
| | - Yuran Su
- Hospital
of Stomatology, Tianjin Medical University, Tianjin 300070, People ’s Republic of China
| | - Yanmei Zhao
- Institute
of Disaster and Emergency Medicine, Tianjin
University, Tianjin 300072, People ’s Republic
of China
| | - Yuna Shang
- Tianjin
Key Laboratory of Structure and Performance for Functional Molecules,
College of Chemistry, Tianjin Normal University, Tianjin 300387, People ’s Republic of China
| |
Collapse
|
|
12
|
An YZ, Strauss FJ, Park JY, Shen YQ, Thoma DS, Lee JS. Membrane fixation enhances guided bone regeneration in standardized calvarial defects: A pre-clinical study. J Clin Periodontol 2022; 49:177-187. [PMID: 34866208 DOI: 10.1111/jcpe.13583] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 10/09/2021] [Accepted: 11/23/2021] [Indexed: 12/21/2022]
Abstract
AIM To determine whether collagen membrane (CM) fixation enhances guided bone regeneration in standardized defects. MATERIALS AND METHODS Four 8-mm-diameter defects were surgically made in eight rabbit calvaria, and randomly allocated into four groups: control (empty), unfixed-CM, fixed-CM, and unfixed-CM with bone graft (BG + CM) (positive control). After 1- and 4-week healing periods, the animals were sacrificed and quantitative reverse transcription polymerase chain reaction, micro-computed tomography, and histological outcomes were assessed. RESULTS At week 1, the expression levels of BMP-2, FGF-2, VEGF, and osteocalcin were significantly higher in the fixed-CM group than in the unfixed-CM and control groups (p < .05). Conversely, cathepsin-K was significantly expressed in the unfixed-CM group. No significant differences in expression markers were observed between the fixed-CM and BG + CM groups (p > .05). At week 4, new bone formation was significantly higher in the fixed-CM group than the unfixed-CM and control groups (p < .05), but similar to the BG + CM group (p > .05). CONCLUSIONS CM fixation enhances the expression of osteogenic factors similar to BG + CM, leading to significantly more new bone formation. This suggests that the osteogenic potential is greater when membranes are fixed, thereby limiting the necessity of membrane-supporting materials to enhance bone formation.
Collapse
Affiliation(s)
- Yin-Zhe An
- Department of Periodontology, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Franz-Josef Strauss
- Clinic of Reconstructive Dentistry, University of Zurich, Zurich, Switzerland
- Department of Conservative Dentistry, Faculty of Dentistry, University of Chile, Santiago, Chile
- Department of Oral Biology, Medical University of Vienna, Vienna, Austria
| | - Jin-Young Park
- Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, Seoul, Republic of Korea
| | - Yu Qin Shen
- Department of Periodontology, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
- Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Daniel Stefan Thoma
- Clinic of Reconstructive Dentistry, University of Zurich, Zurich, Switzerland
| | - Jung-Seok Lee
- Department of Oral Biology, Medical University of Vienna, Vienna, Austria
- Department of Periodontology, Research Institute for Periodontal Regeneration, College of Dentistry, Yonsei University, Seoul, Republic of Korea
- Innovation Research and Support Center for Dental Science, Yonsei University Dental Hospital, Seoul, Republic of Korea
| |
Collapse
|
|
13
|
Zhang Y, Ding Y, Li X, Zhang Z, Zhang X, Chen Y, Yang Z, Shi Y, Hu ZW. Enzyme-instructed self-assembly enabled fluorescence light-up for alkaline phosphatase detection. Talanta 2021; 239:123078. [PMID: 34823863 DOI: 10.1016/j.talanta.2021.123078] [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] [Received: 08/31/2021] [Revised: 11/11/2021] [Accepted: 11/16/2021] [Indexed: 11/27/2022]
Abstract
Alkaline phosphatase (ALP) exists in both normal and pathological tissues. Spatiotemporal variations in ALP levels can reveal its potential physiological functions and changes that occur during pathological conditions. However, it is still challenging to exploit fluorescent probes that can measure ALP activity under good spatial and temporal resolutions. Herein, enzyme-instructed self-assembly (EISA) was used to construct a high-performing analytical tool (MN-pY) to probe ALP activity. MN-pY alone (free state) showed negligible fluorescence but presented an almost 13-fold increase in fluorescence intensity in the presence of ALP (assembly state). Mechanism study indicated the increase in fluorescence intensity was due to hydrogelation and formation of supramolecular fibrils, mainly consisting of dephosphorylated MN-Y. The dephosphorylation and further fibrillation of MN-pY could induce the formation of a "hydrophobic pocket", leading to a further increase in fluorescence intensity. Moreover, MN-pY could selectively illuminate HeLa cells with a higher ALP expression but not LO2 cells with lower ALP levels, promising a potential application in cancer diagnosis.
Collapse
Affiliation(s)
- Yiming Zhang
- State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, And Collaboration Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, China
| | - Yinghao Ding
- State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, And Collaboration Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, China
| | - Xinxin Li
- State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, And Collaboration Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, China
| | - Zhenghao Zhang
- State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, And Collaboration Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, China
| | - Xiangyang Zhang
- State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, And Collaboration Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, China
| | - Yumiao Chen
- State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, And Collaboration Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, China
| | - Zhimou Yang
- State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, And Collaboration Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, China
| | - Yang Shi
- State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, And Collaboration Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, China.
| | - Zhi-Wen Hu
- State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, And Collaboration Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, China.
| |
Collapse
|
|
14
|
Liu T, Xu J, Pan X, Ding Z, Xie H, Wang X, Xie H. Advances of adipose-derived mesenchymal stem cells-based biomaterial scaffolds for oral and maxillofacial tissue engineering. Bioact Mater 2021; 6:2467-2478. [PMID: 33553828 PMCID: PMC7850942 DOI: 10.1016/j.bioactmat.2021.01.015] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 01/03/2021] [Accepted: 01/11/2021] [Indexed: 02/05/2023] Open
Abstract
The management of oral and maxillofacial tissue defects caused by tumors, trauma, and congenital or acquired deformities has been a major challenge for surgeons over the last few decades. Autologous tissue transplantation, the gold standard of tissue reconstruction, is a valid method for repairing the oral and maxillofacial functions and aesthetics. However, several limitations hinder its clinical applications including complications of donor sites, limited tissue volume, and uncertain long-term outcomes. Adipose-derived mesenchymal stem cells (ADMSCs) widely exist in adipose tissue and can be easily obtained through liposuction. Like the bone marrow-derived mesenchymal stem cells (BMSCs), ADMSCs also have the multi-pluripotent potencies to differentiate into osteoblasts, chondrocytes, neurons, and myocytes. Therefore, the multilineage capacity of ADMSCs makes them valuable for cell-based medical therapies. In recent years, researchers have developed many candidates of ADMSCs-based biomaterial scaffolds to cater for the needs of oral and maxillofacial tissue engineering due to their superior performance. This review presents the advances and applications of ADMSCs-based biomaterial scaffolds, and explores their tissue engineering prospects in oral and maxillofacial reconstructions.
Collapse
Affiliation(s)
- Tong Liu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Jia Xu
- The Key Laboratory of Oral Biomedicine, Jiangxi Province, School of Stomatology, Nanchang University, Nanchang, 330006, China
| | - Xun Pan
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Zhangfan Ding
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Hao Xie
- General Surgery Department, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, 241000, China
| | - Xiaoyi Wang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Huixu Xie
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| |
Collapse
|
|
15
|
Da Silva D, Crous A, Abrahamse H. Photobiomodulation: An Effective Approach to Enhance Proliferation and Differentiation of Adipose-Derived Stem Cells into Osteoblasts. Stem Cells Int 2021; 2021:8843179. [PMID: 33833810 PMCID: PMC8012132 DOI: 10.1155/2021/8843179] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 03/07/2021] [Accepted: 03/11/2021] [Indexed: 01/07/2023] Open
Abstract
Osteoporosis is regarded as the most common chronic metabolic bone condition in humans. In osteoporosis, bone mesenchymal stem cells (MSCs) have reduced cellular function. Regenerative medicine using adipose-derived stem cell (ADSC) transplantation can promote the growth and strength of new bones, improve bone stability, and reduce the risk of fractures. Various methods have been attempted to differentiate ADSCs to functioning specialized cells for prospective clinical application. However, commonly used therapies have resulted in damage to the donor site and morbidity, immune reactions, carcinogenic generation, and postoperative difficulties. Photobiomodulation (PBM) improves ADSC differentiation and proliferation along with reducing clinical difficulties such as treatment failures to common drug therapies and late initiation of treatment. PBM is a noninvasive, nonthermal treatment that encourages cells to produce more energy and to undergo self-repair by using visible green and red and invisible near-infrared (NIR) radiation. The use of PBM for ADSC proliferation and differentiation has been widely studied with multiple outcomes observed due to laser fluence and wavelength dependence. In this article, the potential for differentiating ADSCs into osteoblasts and the various methods used, including biological induction, chemical induction, and PBM, will be addressed. Likewise, the optimal laser parameters that could improve the proliferation and differentiation of ADSC, translating into clinical success, will be commented on.
Collapse
Affiliation(s)
- Daniella Da Silva
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg, South Africa 2028
| | - Anine Crous
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg, South Africa 2028
| | - Heidi Abrahamse
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg, South Africa 2028
| |
Collapse
|
|
16
|
Ofiteru AM, Becheru DF, Gharbia S, Balta C, Herman H, Mladin B, Ionita M, Hermenean A, Burns JS. Qualifying Osteogenic Potency Assay Metrics for Human Multipotent Stromal Cells: TGF-β2 a Telling Eligible Biomarker. Cells 2020; 9:E2559. [PMID: 33260388 PMCID: PMC7760953 DOI: 10.3390/cells9122559] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 11/18/2020] [Accepted: 11/24/2020] [Indexed: 02/06/2023] Open
Abstract
Potency assays are critical for regenerative medicine, addressing the known challenge of functional heterogeneity among human multipotent stromal cells (hMSC). Necessary laboratory cell expansion allows analysis before implantation in the patient. Levels of induction of five signature gene biomarkers, ALPL, COL1A2, DCN, ELN and RUNX2, constituted a previously reported proof-of-principle osteogenic potency assay. We tested assay modification to enhance reproducibility using six consistent bone marrow derived hBM-MSC and explored applicability to three adipose tissue derived hAT-MSC. Using a potent proprietary osteogenic induction factor, the GUSB/YWAHZ reference gene pair provided real time PCR consistency. The novel assay conditions supported the concept that genes encoding extracellular matrix proteins one week after osteogenic induction were informative. Nonetheless, relatively low induction of COL1A2 and ELN encouraged search for additional biomarkers. TGFB2 mRNA induction, important for osteogenic commitment, was readily quantifiable in both hBM-MSC and hAT-MSC. Combined with DCN, TGFB2 mRNA induction data provided discriminatory power for resolving donor-specific heterogeneity. Histomorphometric decorin and TGF-β2 protein expression patterns in eight-week heterotopic bone implants also discriminated the two non-bone-forming hMSC. We highlight progress towards prompt osteogenic potency assays, needed by current clinical trials to accelerate improved intervention with enhanced stem cell therapy for serious bone fractures.
Collapse
Affiliation(s)
- Augustin M. Ofiteru
- Faculty of Medical Engineering, University Politehnica of Bucharest, Gh Polizu 1-7, 011061 Bucharest, Romania; (D.F.B.); (M.I.)
| | - Diana F. Becheru
- Faculty of Medical Engineering, University Politehnica of Bucharest, Gh Polizu 1-7, 011061 Bucharest, Romania; (D.F.B.); (M.I.)
- Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Gh Polizu 1-7, 011061 Bucharest, Romania
| | - Sami Gharbia
- “Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Rebreanu, 310414 Arad, Romania; (S.G.); (C.B.); (H.H.); (B.M.); (A.H.)
| | - Cornel Balta
- “Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Rebreanu, 310414 Arad, Romania; (S.G.); (C.B.); (H.H.); (B.M.); (A.H.)
| | - Hildegard Herman
- “Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Rebreanu, 310414 Arad, Romania; (S.G.); (C.B.); (H.H.); (B.M.); (A.H.)
| | - Bianca Mladin
- “Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Rebreanu, 310414 Arad, Romania; (S.G.); (C.B.); (H.H.); (B.M.); (A.H.)
| | - Mariana Ionita
- Faculty of Medical Engineering, University Politehnica of Bucharest, Gh Polizu 1-7, 011061 Bucharest, Romania; (D.F.B.); (M.I.)
| | - Anca Hermenean
- “Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Rebreanu, 310414 Arad, Romania; (S.G.); (C.B.); (H.H.); (B.M.); (A.H.)
| | - Jorge S. Burns
- Faculty of Medical Engineering, University Politehnica of Bucharest, Gh Polizu 1-7, 011061 Bucharest, Romania; (D.F.B.); (M.I.)
- Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy
| |
Collapse
|
|
17
|
Gantenbein B, Tang S, Guerrero J, Higuita-Castro N, Salazar-Puerta AI, Croft AS, Gazdhar A, Purmessur D. Non-viral Gene Delivery Methods for Bone and Joints. Front Bioeng Biotechnol 2020; 8:598466. [PMID: 33330428 PMCID: PMC7711090 DOI: 10.3389/fbioe.2020.598466] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 10/26/2020] [Indexed: 12/12/2022] Open
Abstract
Viral carrier transport efficiency of gene delivery is high, depending on the type of vector. However, viral delivery poses significant safety concerns such as inefficient/unpredictable reprogramming outcomes, genomic integration, as well as unwarranted immune responses and toxicity. Thus, non-viral gene delivery methods are more feasible for translation as these allow safer delivery of genes and can modulate gene expression transiently both in vivo, ex vivo, and in vitro. Based on current studies, the efficiency of these technologies appears to be more limited, but they are appealing for clinical translation. This review presents a summary of recent advancements in orthopedics, where primarily bone and joints from the musculoskeletal apparatus were targeted. In connective tissues, which are known to have a poor healing capacity, and have a relatively low cell-density, i.e., articular cartilage, bone, and the intervertebral disk (IVD) several approaches have recently been undertaken. We provide a brief overview of the existing technologies, using nano-spheres/engineered vesicles, lipofection, and in vivo electroporation. Here, delivery for microRNA (miRNA), and silencing RNA (siRNA) and DNA plasmids will be discussed. Recent studies will be summarized that aimed to improve regeneration of these tissues, involving the delivery of bone morphogenic proteins (BMPs), such as BMP2 for improvement of bone healing. For articular cartilage/osteochondral junction, non-viral methods concentrate on targeted delivery to chondrocytes or MSCs for tissue engineering-based approaches. For the IVD, growth factors such as GDF5 or GDF6 or developmental transcription factors such as Brachyury or FOXF1 seem to be of high clinical interest. However, the most efficient method of gene transfer is still elusive, as several preclinical studies have reported many different non-viral methods and clinical translation of these techniques still needs to be validated. Here we discuss the non-viral methods applied for bone and joint and propose methods that can be promising in clinical use.
Collapse
Affiliation(s)
- Benjamin Gantenbein
- Tissue Engineering for Orthopaedics and Mechanobiology, Department for BioMedical Research (DBMR), Faculty of Medicine, University of Bern, Bern, Switzerland.,Department of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Shirley Tang
- Department of Biomedical Engineering and Department of Orthopaedics, Spine Research Institute Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, United States
| | - Julien Guerrero
- Tissue Engineering for Orthopaedics and Mechanobiology, Department for BioMedical Research (DBMR), Faculty of Medicine, University of Bern, Bern, Switzerland.,Department of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Natalia Higuita-Castro
- Department of Biomedical Engineering and Department of Surgery, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, United States
| | - Ana I Salazar-Puerta
- Department of Biomedical Engineering and Department of Surgery, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, United States
| | - Andreas S Croft
- Tissue Engineering for Orthopaedics and Mechanobiology, Department for BioMedical Research (DBMR), Faculty of Medicine, University of Bern, Bern, Switzerland.,Department of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Amiq Gazdhar
- Department of Pulmonary Medicine, Inselspital, University Hospital, University of Bern, Bern, Switzerland
| | - Devina Purmessur
- Department of Biomedical Engineering and Department of Orthopaedics, Spine Research Institute Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, United States
| |
Collapse
|
|
18
|
Jalal AR, Dixon JE. Efficient Delivery of Transducing Polymer Nanoparticles for Gene-Mediated Induction of Osteogenesis for Bone Regeneration. Front Bioeng Biotechnol 2020; 8:849. [PMID: 32850720 PMCID: PMC7419434 DOI: 10.3389/fbioe.2020.00849] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Accepted: 07/01/2020] [Indexed: 01/08/2023] Open
Abstract
Developing non-viral gene therapy vectors that both protect and functionally deliver nucleic acid cargoes will be vital if gene augmentation and editing strategies are to be effectively combined with advanced regenerative medicine approaches. Currently such methodologies utilize high concentrations of recombinant growth factors, which result in toxicity and off-target effects. Herein we demonstrate the use of modified cell penetrating peptides (CPPs), termed Glycosaminoglycan (GAG)-binding Enhanced Transduction (GET) peptides with plasmid DNA (pDNA) encapsulated poly (lactic-co-glycolic acid) PLGA nanoparticles (pDNA-encapsulated PLGA NPs). In order to encapsulate the pDNA, it was first condensed with a cationic low molecular weight Poly L-Lysine (PLL) into 30-60 nm NPs followed by encapsulation in PLGA NPs by double emulsion; yielding encapsulation efficiencies (EE) of ∼30%. PLGA NPs complexed with GET peptides show enhanced intracellular delivery (up to sevenfold) and transfection efficiencies (up to five orders of magnitude). Moreover, the pDNA cargo has enhanced protection from nucleases (such as DNase I) promoting their translatability. As an example, we show these NPs efficiently deliver pBMP2 which can promote osteogenic differentiation in vitro. Gene delivery to human Mesenchymal Stromal Cells (hMSCs) inducing their osteogenic programming was confirmed by Alizarin red calcium staining and bone lineage specific gene expression (Q RT-PCR). By combining simplistic and FDA-approved PLGA polymer nanotechnology with the GET delivery system, therapeutic non-viral vectors could have significant impact in future cellular therapy and regenerative medicine applications.
Collapse
Affiliation(s)
| | - James E. Dixon
- Regenerative Medicine and Cellular Therapies Division, The University of Nottingham Biodiscovery Institute (BDI), School of Pharmacy, University of Nottingham, Nottingham, United Kingdom
| |
Collapse
|
|
19
|
Wang P, Logeart-Avramoglou D, Petite H, Goncalves C, Midoux P, Perche F, Pichon C. Co-delivery of NS1 and BMP2 mRNAs to murine pluripotent stem cells leads to enhanced BMP-2 expression and osteogenic differentiation. Acta Biomater 2020; 108:337-346. [PMID: 32251783 DOI: 10.1016/j.actbio.2020.03.045] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 03/05/2020] [Accepted: 03/30/2020] [Indexed: 12/26/2022]
Abstract
Application of messenger RNA (mRNA) for bone regeneration is a promising alternative to DNA, recombinant proteins and peptides. However, exogenous in vitro transcribed mRNA (IVT mRNA) triggers innate immune response resulting in mRNA degradation and translation inhibition. Inspired by the ability of viral immune evasion proteins to inhibit host cell responses against viral RNA, we applied non-structural protein-1 (NS1) from Influenza A virus (A/Texas/36/1991) as an IVT mRNA enhancer. We evidenced a dose-dependent blocking of RNA sensors by NS1 expression. The co-delivery of NS1 mRNA with mRNA of reporter genes significantly increased the translation efficiency. Interestingly, unlike the use of nucleosides modification, NS1-mediated mRNA translation enhancement does not dependent to cell type. Dual delivery of NS1 mRNA and BMP-2 mRNA to murine pluripotent stem cells (C3H10T1/2), promoted osteogenic differentiation evidenced by enhanced expression of osteoblastic markers (e.g. alkaline phosphatase, type I collagen, osteopontin, and osteocalcin), and extracellular mineralization. Overall, these results support the adjuvant potentiality of NS1 for mRNA-based regenerative therapies. STATEMENT OF SIGNIFICANCE: mRNA therapy has the potential to improve the efficiency of nucleic acid based regenerative medicine. Up to now, the incorporation of expensive modified nucleotides is a common way to avoid IVT mRNA-induced detrimental immunogenicity. We here introduce co-delivery of Influenza virus immune evasion protein-NS1 coding mRNA as a strategy to suppress RNA sensors for maximizing IVT mRNA expression. An increased osteogenic commitment of pluripotent stem cells was observed after BMP2 mRNA and NS1 mRNA delivery. This study revealed how applying non-modified mRNA with NS1 could be a promising alternative as a therapeutic in bone regeneration.
Collapse
Affiliation(s)
- Pinpin Wang
- Centre de Biophysique Moléculaire, UPR 4301 CNRS, Rue Charles Sadron, 45071 Orléans, France
| | | | - Hervé Petite
- Université de Paris, CNRS, INSERM, B3OA, 10 Avenue de Verdun, 75010 Paris, France
| | - Cristine Goncalves
- Centre de Biophysique Moléculaire, UPR 4301 CNRS, Rue Charles Sadron, 45071 Orléans, France
| | - Patrick Midoux
- Centre de Biophysique Moléculaire, UPR 4301 CNRS, Rue Charles Sadron, 45071 Orléans, France
| | - Federico Perche
- Centre de Biophysique Moléculaire, UPR 4301 CNRS, Rue Charles Sadron, 45071 Orléans, France
| | - Chantal Pichon
- Centre de Biophysique Moléculaire, UPR 4301 CNRS, Rue Charles Sadron, 45071 Orléans, France; Faculty of Sciences and Techniques, University of Orléans, France.
| |
Collapse
|
|
20
|
Kronemberger GS, Matsui RAM, Miranda GDASDCE, Granjeiro JM, Baptista LS. Cartilage and bone tissue engineering using adipose stromal/stem cells spheroids as building blocks. World J Stem Cells 2020; 12:110-122. [PMID: 32184936 PMCID: PMC7062040 DOI: 10.4252/wjsc.v12.i2.110] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 10/19/2019] [Accepted: 01/15/2020] [Indexed: 02/06/2023] Open
Abstract
Scaffold-free techniques in the developmental tissue engineering area are designed to mimic in vivo embryonic processes with the aim of biofabricating, in vitro, tissues with more authentic properties. Cell clusters called spheroids are the basis for scaffold-free tissue engineering. In this review, we explore the use of spheroids from adult mesenchymal stem/stromal cells as a model in the developmental engineering area in order to mimic the developmental stages of cartilage and bone tissues. Spheroids from adult mesenchymal stromal/stem cells lineages recapitulate crucial events in bone and cartilage formation during embryogenesis, and are capable of spontaneously fusing to other spheroids, making them ideal building blocks for bone and cartilage tissue engineering. Here, we discuss data from ours and other labs on the use of adipose stromal/stem cell spheroids in chondrogenesis and osteogenesis in vitro. Overall, recent studies support the notion that spheroids are ideal "building blocks" for tissue engineering by “bottom-up” approaches, which are based on tissue assembly by advanced techniques such as three-dimensional bioprinting. Further studies on the cellular and molecular mechanisms that orchestrate spheroid fusion are now crucial to support continued development of bottom-up tissue engineering approaches such as three-dimensional bioprinting.
Collapse
Affiliation(s)
- Gabriela S Kronemberger
- Laboratory of Tissue Bioengineering, Directory of Metrology Applied to Life Sciences, National Institute of Metrology, Quality and Technology (INMETRO), Duque de Caxias, RJ 25250-020, Brazil
- Post-graduate Program in Translational Biomedicine (Biotrans), Unigranrio, Campus I, Duque de Caxias, RJ 25250-020, Brazil
| | - Renata Akemi Morais Matsui
- Laboratory of Tissue Bioengineering, Directory of Metrology Applied to Life Sciences, National Institute of Metrology, Quality and Technology (INMETRO), Duque de Caxias, RJ 25250-020, Brazil
- Post-graduate Program in Biotechnology, National Institute of Metrology, Quality and Technology (INMETRO), Duque de Caxias, RJ 25250-020, Brazil
| | - Guilherme de Almeida Santos de Castro e Miranda
- Laboratory of Tissue Bioengineering, Directory of Metrology Applied to Life Sciences, National Institute of Metrology, Quality and Technology (INMETRO), Duque de Caxias, RJ 25250-020, Brazil
- Federal University of Rio de Janeiro (UFRJ), Campus Duque de Caxias, Duque de Caxias, RJ 25250-020, Brazil
| | - José Mauro Granjeiro
- Laboratory of Tissue Bioengineering, Directory of Metrology Applied to Life Sciences, National Institute of Metrology, Quality and Technology (INMETRO), Duque de Caxias, RJ 25250-020, Brazil
- Post-graduate Program in Biotechnology, National Institute of Metrology, Quality and Technology (INMETRO), Duque de Caxias, RJ 25250-020, Brazil
- Laboratory of Clinical Research in Odontology, Fluminense Federal University (UFF), Niterói 25255-030 Brazil
| | - Leandra Santos Baptista
- Laboratory of Tissue Bioengineering, Directory of Metrology Applied to Life Sciences, National Institute of Metrology, Quality and Technology (INMETRO), Duque de Caxias, RJ 25250-020, Brazil
- Post-graduate Program in Translational Biomedicine (Biotrans), Unigranrio, Campus I, Duque de Caxias, RJ 25250-020, Brazil
- Post-graduate Program in Biotechnology, National Institute of Metrology, Quality and Technology (INMETRO), Duque de Caxias, RJ 25250-020, Brazil
- Multidisciplinary Center for Biological Research (Numpex-Bio), Federal University of Rio de Janeiro (UFRJ) Campus Duque de Caxias, Duque de Caxias, RJ 25245-390, Brazil
| |
Collapse
|
|
21
|
Dębski T, Kurzyk A, Ostrowska B, Wysocki J, Jaroszewicz J, Święszkowski W, Pojda Z. Scaffold vascularization method using an adipose-derived stem cell (ASC)-seeded scaffold prefabricated with a flow-through pedicle. Stem Cell Res Ther 2020; 11:34. [PMID: 31973733 PMCID: PMC6979360 DOI: 10.1186/s13287-019-1535-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Revised: 11/18/2019] [Accepted: 12/19/2019] [Indexed: 02/06/2023] Open
Abstract
Background Vascularization is important for the clinical application of tissue engineered products. Both adipose-derived stem cells (ASCs) and surgical prefabrication can be used to induce angiogenesis in scaffolds. Our aim was to compare the angiogenic potential of ASC-seeded scaffolds combined with scaffold prefabrication with that of non-seeded, non-prefabricated scaffolds. Methods For prefabrication, functional blood vessels were introduced into the scaffold using a flow-through pedicle system. ASCs were isolated from rat fat deposits. Three-dimensional-printed cylindrical poly-ε-caprolactone scaffolds were fabricated by fused deposition modelling. Three groups, each containing six rats, were investigated by using non-seeded, ASC-seeded, and osteogenic induced ASC-seeded scaffolds. In each group, one rat was implanted with two scaffolds in the inguinal region. On the right side, a scaffold was implanted subcutaneously around the inferior epigastric vessels (classic prefabrication group). On the left side, the inferior epigastric vessels were placed inside the prefabricated scaffold in the flow-through pedicle system (flow-through prefabrication group). The vessel density and vascular architecture were examined histopathologically and by μCT imaging, respectively, at 2 months after implantation. Results The mean vessel densities were 10- and 5-fold higher in the ASC-seeded and osteogenic induced ASC-seeded scaffolds with flow-through prefabrication, respectively, than in the non-seeded classic prefabricated group (p < 0.001). μCT imaging revealed functional vessels within the scaffold. Conclusion ASC-seeded scaffolds with prefabrication showed significantly improved scaffold vasculogenesis and could be useful for application to tissue engineering products in the clinical settings.
Collapse
Affiliation(s)
- Tomasz Dębski
- Department of Regenerative Medicine, Maria Sklodowska Curie Institute - Oncology Center, Roentgena 5, 02-781, Warsaw, Poland.
| | - Agata Kurzyk
- Department of Regenerative Medicine, Maria Sklodowska Curie Institute - Oncology Center, Roentgena 5, 02-781, Warsaw, Poland
| | - Barbara Ostrowska
- Materials Design Division, Faculty of Materials Science and Engineering, Warsaw University of Technology, Woloska 141, 02-507, Warsaw, Poland
| | - Juliusz Wysocki
- Department of Regenerative Medicine, Maria Sklodowska Curie Institute - Oncology Center, Roentgena 5, 02-781, Warsaw, Poland
| | - Jakub Jaroszewicz
- Materials Design Division, Faculty of Materials Science and Engineering, Warsaw University of Technology, Woloska 141, 02-507, Warsaw, Poland
| | - Wojciech Święszkowski
- Materials Design Division, Faculty of Materials Science and Engineering, Warsaw University of Technology, Woloska 141, 02-507, Warsaw, Poland
| | - Zygmunt Pojda
- Department of Regenerative Medicine, Maria Sklodowska Curie Institute - Oncology Center, Roentgena 5, 02-781, Warsaw, Poland
| |
Collapse
|
|
22
|
Choi J, Bae T, Byambasuren N, Park SH, Jo CH, Kim D, Hur JK, Hwang NS. CRISPR-Cpf1 Activation of Endogenous BMP4 Gene for Osteogenic Differentiation of Umbilical-Cord-Derived Mesenchymal Stem Cells. MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT 2020; 17:309-316. [PMID: 32021879 PMCID: PMC6994413 DOI: 10.1016/j.omtm.2019.12.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 12/17/2019] [Indexed: 12/11/2022]
Abstract
The CRISPR systems provide powerful genome-editing tools for wide applications in biological and medical research fields. However, the safety issue due to off-target effects of CRISPR has been one of the major hindrances of its application to regenerative medicine. The conventional CRISPR system has the intrinsic danger of inducing unpredictable mutations at non-targeted genomic loci via erroneous double-strand DNA breaks (DSBs). In this study, we demonstrate a safety-enhanced application of a recently discovered CRISPR-Cpf1 for targeted gene activation, without DNA double-strand break, to facilitate osteogenic differentiation of human umbilical-cord-derived mesenchymal stem cells (UC-MSCs). To this end, we developed a catalytically inactive AsCpf1 fused to tripartite transcription activator domain (dAsCpf1-VPR) that can induce upregulation of targeted gene expression in mammalian cells. We observed that the CRISPR-dAsCpf1-VPR activator can be applied to enhance the osteogenic differentiation of human UC-MSCs, via increasing the expression level of endogenous BMP4 gene. The results suggested that the CRISPR-Cpf1 activator provides versatile methods applicable for bone regeneration and regenerative medicine.
Collapse
Affiliation(s)
- Jaehoon Choi
- School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul, Korea
| | - Taegeun Bae
- Department of Medicine, Graduate School, Kyung Hee University, Seoul, Korea
| | - Ninj Byambasuren
- Interdisciplinary Program in Bioengineering, Institute of Bio Engineering, Seoul National University, Seoul, Korea
| | - Seong-Ho Park
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Korea
| | - Chris H Jo
- Department of Orthopedic Surgery, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Dokyoung Kim
- Department of Anatomy and Neurobiology, College of Medicine, Kyung Hee University, Seoul, Korea.,Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Korea.,Center for Converging Humanities, Kyung Hee University, Seoul, Korea.,Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Kyung Hee University, Seoul, Korea
| | - Junho K Hur
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Korea.,Department of Pathology, College of Medicine, Kyung Hee Unversity, Seoul, Korea
| | - Nathaniel S Hwang
- School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul, Korea.,Interdisciplinary Program in Bioengineering, Institute of Bio Engineering, Seoul National University, Seoul, Korea
| |
Collapse
|
|
23
|
Yu X, Hu L, Wang G, Huang T, Wei W, Wang M, Xia Z. DNA-mediated biomineralization of calcium-deficient hydroxyapatite for bone tissue engineering. NEW J CHEM 2020. [DOI: 10.1039/c9nj04921e] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
A random DNA duplex was utilized as the biotemplate to mediate the biomineralization of calcium-deficient hydroxyapatite with osteoconductive properties.
Collapse
Affiliation(s)
- Xinsheng Yu
- School of Pharmaceutical Sciences
- Chongqing University
- Chongqing
- China
| | - Lianzhe Hu
- Chongqing Key Laboratory of Green Synthesis and Applications
- College of Chemistry
- Chongqing Normal University
- Chongqing
- China
| | - Guixia Wang
- College of Chemistry and Chemical Engineering, and Henan Key Laboratory of Function-Oriented Porous Materials
- Luoyang Normal University
- Luoyang 471934
- China
| | - Ting Huang
- School of Pharmaceutical Sciences
- Chongqing University
- Chongqing
- China
| | - Weili Wei
- School of Pharmaceutical Sciences
- Chongqing University
- Chongqing
- China
| | - Min Wang
- School of Pharmaceutical Sciences
- Chongqing University
- Chongqing
- China
| | - Zhining Xia
- School of Pharmaceutical Sciences
- Chongqing University
- Chongqing
- China
| |
Collapse
|
|
24
|
Progress and Applications of Polyphosphate in Bone and Cartilage Regeneration. BIOMED RESEARCH INTERNATIONAL 2019; 2019:5141204. [PMID: 31346519 PMCID: PMC6620837 DOI: 10.1155/2019/5141204] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 04/29/2019] [Accepted: 06/11/2019] [Indexed: 02/06/2023]
Abstract
Patients with bone and cartilage defects due to infection, tumors, and trauma are quite common. Repairing bone and cartilage defects is thus a major problem for clinicians. Autologous and artificial bone transplantations are associated with many challenges, such as limited materials and immune rejection. Bone and cartilage regeneration has become a popular research topic. Inorganic polyphosphate (polyP) is a widely occurring biopolymer with high-energy phosphoanhydride bonds that exists in organisms from bacteria to mammals. Much data indicate that polyP acts as a regulator of gene expression in bone and cartilage tissues and exerts morphogenetic effects on cells involved in bone and cartilage formation. Exposure of these cells to polyP leads to the increase of cytokines that promote the differentiation of mesenchymal stem cells into osteoblasts, accelerates the osteoblast mineralization process, and inhibits the differentiation of osteoclast precursors to functionally active osteoclasts. PolyP-based materials have been widely reported in in vivo and in vitro studies. This paper reviews the current cellular mechanisms and material applications of polyP in bone and cartilage regeneration.
Collapse
|
|
25
|
Torres-Torrillas M, Rubio M, Damia E, Cuervo B, Del Romero A, Peláez P, Chicharro D, Miguel L, Sopena JJ. Adipose-Derived Mesenchymal Stem Cells: A Promising Tool in the Treatment of Musculoskeletal Diseases. Int J Mol Sci 2019; 20:ijms20123105. [PMID: 31242644 PMCID: PMC6627452 DOI: 10.3390/ijms20123105] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Revised: 06/20/2019] [Accepted: 06/20/2019] [Indexed: 02/08/2023] Open
Abstract
Chronic musculoskeletal (MSK) pain is one of the most common medical complaints worldwide and musculoskeletal injuries have an enormous social and economical impact. Current pharmacological and surgical treatments aim to relief pain and restore function; however, unsatiscactory outcomes are commonly reported. In order to find an accurate treatment to such pathologies, over the last years, there has been a significantly increasing interest in cellular therapies, such as adipose-derived mesenchymal stem cells (AMSCs). These cells represent a relatively new strategy in regenerative medicine, with many potential applications, especially regarding MSK disorders, and preclinical and clinical studies have demonstrated their efficacy in muscle, tendon, bone and cartilage regeneration. Nevertheless, several worries about their safety and side effects at long-term remain unsolved. This article aims to review the current state of AMSCs therapy in the treatment of several MSK diseases and their clinical applications in veterinary and human medicine.
Collapse
Affiliation(s)
- Marta Torres-Torrillas
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain.
| | - Monica Rubio
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain.
- García Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain.
| | - Elena Damia
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain.
| | - Belen Cuervo
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain.
| | - Ayla Del Romero
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain.
| | - Pau Peláez
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain.
| | - Deborah Chicharro
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain.
| | - Laura Miguel
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain.
| | - Joaquin J Sopena
- Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain.
- García Cugat Foundation CEU-UCH Chair of Medicine and Regenerative Surgery, CEU Cardenal Herrera University, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain.
| |
Collapse
|
|
26
|
Youn YH, Lee SJ, Choi GR, Lee HR, Lee D, Heo DN, Kim BS, Bang JB, Hwang YS, Correlo VM, Reis RL, Im SG, Kwon IK. Simple and facile preparation of recombinant human bone morphogenetic protein-2 immobilized titanium implant via initiated chemical vapor deposition technique to promote osteogenesis for bone tissue engineering application. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2019; 100:949-958. [PMID: 30948131 DOI: 10.1016/j.msec.2019.03.048] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Revised: 09/13/2018] [Accepted: 03/13/2019] [Indexed: 01/07/2023]
Abstract
Over the past few decades, titanium (Ti) implants have been widely used to repair fractured bones. To promote osteogenesis, immobilization of osteoinductive agents, such as recombinant human bone morphogenic protein-2 (rhBMP2), onto the Ti surface is required. In this study, we prepared rhBMP2 immobilized on glycidyl methacrylate (GMA) deposited Ti surface through initiated chemical vapor deposition (iCVD) technique. After preparation, the bio-functionalized Ti surface was characterized by physicochemical analysis. For in vitro analysis, the developed Ti was evaluated by cell proliferation, alkaline phosphatase activity, calcium deposition, and real-time polymerase chain reaction to verify their osteogenic activity against human adipose-derived stem cells (hASCs). The GMA deposited Ti surface was found to effectively immobilize a large dose of rhBMP2 as compared to untreated Ti. Additionally, rhBMP2 immobilized on Ti showed significantly enhanced osteogenic differentiation and increased calcium deposition with nontoxic cell viability. These results clearly confirm that our strategy may provide a simple, solvent-free strategy to prepare an osteoinductive Ti surface for bone tissue engineering applications.
Collapse
Affiliation(s)
- Yun Hee Youn
- Interdisciplinary Program for Bioengineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea; 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark - Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, GMR, Portugal
| | - Sang Jin Lee
- Department of Dental Materials, School of Dentistry, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea
| | - Go Ro Choi
- Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea
| | - Hak Rae Lee
- Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea
| | - Donghyun Lee
- Department of Dental Materials, School of Dentistry, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea
| | - Dong Nyoung Heo
- Department of Dental Materials, School of Dentistry, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea
| | - Byung-Soo Kim
- Interdisciplinary Program for Bioengineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea; School of Chemical and Biological Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea
| | - Jae Beum Bang
- Department of Dental Education, School of Dentistry, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea
| | - Yu-Shik Hwang
- Department of Maxillofacial Biomedical Engineering, School of Dentistry, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea
| | - Vitor M Correlo
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark - Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, GMR, Portugal
| | - Rui L Reis
- 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark - Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, GMR, Portugal; Department of Dental Materials, School of Dentistry, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea
| | - Sung Gap Im
- Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
| | - Il Keun Kwon
- Department of Dental Materials, School of Dentistry, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
| |
Collapse
|
|
27
|
Wu X, Zhang Y, Xing Y, Zhao B, Zhou C, Wen Y, Xu X. High-fat and high-glucose microenvironment decreases Runx2 and TAZ expression and inhibits bone regeneration in the mouse. J Orthop Surg Res 2019; 14:55. [PMID: 30777111 PMCID: PMC6380030 DOI: 10.1186/s13018-019-1084-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Accepted: 02/01/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) and hyperlipidemia are negatively related to bone regeneration. The aim of this study was to evaluate the effect of high-fat and high-glucose microenvironment on bone regeneration and to detect the expression of runt-related transcription factor 2 (Runx2) and transcriptional co-activator with PDZ-binding domain (TAZ) during this process. METHODS After establishing a high-fat and high-glucose mouse model, a 1 mm × 1.5 mm bone defect was developed in the mandible. On days 7, 14, and 28 after operation, bone regeneration was evaluated by hematoxylin-eosin staining, Masson staining, TRAP staining, and immunohistochemistry, while Runx2 and TAZ expression were detected by immunohistochemistry, RT-PCR, and Western blot analysis. RESULTS Our results showed that the inhibition of bone regeneration in high-fat and high-glucose group was the highest among the four groups. In addition, the expression of Runx2 in high-fat, high-glucose, and high-fat and high-glucose groups was weaker than that in the control group, but the expression of TAZ only showed a decreasing trend in the high-fat and high-glucose group during bone regeneration. CONCLUSIONS In conclusion, these results suggest that high-fat and high-glucose microenvironment inhibits bone regeneration, which may be related to the inhibition of Runx2 and TAZ expression.
Collapse
Affiliation(s)
- Xuan Wu
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, 250012 Shandong People’s Republic of China
- School of Stomatology, Shandong University, No. 44-1, Wenhua Xi Road, Jinan, China
| | - Yunpeng Zhang
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, 250012 Shandong People’s Republic of China
- School of Stomatology, Shandong University, No. 44-1, Wenhua Xi Road, Jinan, China
| | - Yixiao Xing
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, 250012 Shandong People’s Republic of China
- School of Stomatology, Shandong University, No. 44-1, Wenhua Xi Road, Jinan, China
| | - Bin Zhao
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, 250012 Shandong People’s Republic of China
- School of Stomatology, Shandong University, No. 44-1, Wenhua Xi Road, Jinan, China
| | - Cong Zhou
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, 250012 Shandong People’s Republic of China
- School of Stomatology, Shandong University, No. 44-1, Wenhua Xi Road, Jinan, China
| | - Yong Wen
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, 250012 Shandong People’s Republic of China
- School of Stomatology, Shandong University, No. 44-1, Wenhua Xi Road, Jinan, China
| | - Xin Xu
- Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, 250012 Shandong People’s Republic of China
- School of Stomatology, Shandong University, No. 44-1, Wenhua Xi Road, Jinan, China
| |
Collapse
|
|
28
|
Lee E, Ko JY, Kim J, Park JW, Lee S, Im GI. Osteogenesis and angiogenesis are simultaneously enhanced in BMP2-/VEGF-transfected adipose stem cells through activation of the YAP/TAZ signaling pathway. Biomater Sci 2019; 7:4588-4602. [DOI: 10.1039/c9bm01037h] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
While bone has the capability to heal itself, there is a great difficulty in reconstituting large bone defects created by heavy trauma or the resection of malignant tumors.
Collapse
Affiliation(s)
- Eugene Lee
- Research Institute for Integrative Regenerative Biomedical Engineering
- Dongguk University
- Goyang 10326
- Republic of Korea
- Department of Orthopaedics
| | - Ji-Yun Ko
- Research Institute for Integrative Regenerative Biomedical Engineering
- Dongguk University
- Goyang 10326
- Republic of Korea
| | - Juyoung Kim
- Research Institute for Integrative Regenerative Biomedical Engineering
- Dongguk University
- Goyang 10326
- Republic of Korea
| | - Jeong-Won Park
- Research Institute for Integrative Regenerative Biomedical Engineering
- Dongguk University
- Goyang 10326
- Republic of Korea
| | - Songhee Lee
- Research Institute for Integrative Regenerative Biomedical Engineering
- Dongguk University
- Goyang 10326
- Republic of Korea
| | - Gun-Il Im
- Research Institute for Integrative Regenerative Biomedical Engineering
- Dongguk University
- Goyang 10326
- Republic of Korea
- Department of Orthopaedics
| |
Collapse
|
|
29
|
Lee SJ, Lee HJ, Kim SY, Seok JM, Lee JH, Kim WD, Kwon IK, Park SY, Park SA. In situ gold nanoparticle growth on polydopamine-coated 3D-printed scaffolds improves osteogenic differentiation for bone tissue engineering applications: in vitro and in vivo studies. NANOSCALE 2018; 10:15447-15453. [PMID: 30091763 DOI: 10.1039/c8nr04037k] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
In this study, we designed scaffolds coated with gold nanoparticles (GNPs) grown on a polydopamine (PDA) coating of a three-dimensional (3D) printed polycaprolactone (PCL) scaffold. Our results demonstrated that the scaffolds developed here may represent an innovative paradigm in bone tissue engineering by inducing osteogenesis as a means of remodeling and healing bone defects.
Collapse
Affiliation(s)
- Sang Jin Lee
- Department of Nature-Inspired Nanoconvergence Systems, Korea Institute of Machinery and Materials, 156 Gajeongbuk-ro, Yuseong-gu, Daejeon 34103, Republic of Korea.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
30
|
Mencía Castaño I, Curtin CM, Duffy GP, O'Brien FJ. Harnessing an Inhibitory Role of miR-16 in Osteogenesis by Human Mesenchymal Stem Cells for Advanced Scaffold-Based Bone Tissue Engineering. Tissue Eng Part A 2018; 25:24-33. [PMID: 29490603 DOI: 10.1089/ten.tea.2017.0460] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
MicroRNA (miRNA) therapeutics is increasingly being developed to either target bone-related diseases such as osteoporosis and osteoarthritis or as the basis for novel bone tissue engineering strategies. A number of miRNAs have been reported as potential osteo-therapeutics but no consensus has yet been established on the optimal target. miR-16 has been studied extensively in nonosteogenic functions and used as functionality reporter target in the development of nonviral miRNA delivery platforms. This study hypothesized that miR-16 may also play an inhibitory role in osteogenesis due to its ability to directly target Smad5 and AcvR2a. This study thus aimed to assess the potential of miR-16 inhibition to increase osteogenesis in human mesenchymal stem cells (hMSCs) using a previously established miRNA delivery platform composed of nanohydroxyapatite (nHA) particles as nonviral vectors in combination with collagen-nHA scaffolds designed specifically for bone repair. Initial results showed that antagomiR-16 delivery efficiently increased the relative levels of both putative targets and Runx2, the key transcription factor for osteogenesis, while also increasing osteocalcin levels. Furthermore, significant increases in mineral calcium deposition by hMSCs were found in both monolayer and most importantly in scaffold-based osteodifferentiation studies, ultimately demonstrating that miR-16 inhibition further enhances the therapeutic potential of a scaffold with known potential for bone repair applications and thus holds significant therapeutic potential as a novel bone tissue engineering strategy. Furthermore, we suggest that harnessing the additional functions known to miR-16 by incorporating either its enhancers or inhibitors to tissue-specific tailored scaffolds provides exciting opportunities for a diverse range of therapeutic indications.
Collapse
Affiliation(s)
- Irene Mencía Castaño
- 1 Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland.,2 Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, Ireland.,3 Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and TCD, Dublin, Ireland
| | - Caroline M Curtin
- 1 Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland.,2 Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, Ireland.,3 Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and TCD, Dublin, Ireland
| | - Garry P Duffy
- 1 Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland.,2 Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, Ireland.,3 Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and TCD, Dublin, Ireland.,4 Department of Anatomy, School of Medicine, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Ireland
| | - Fergal J O'Brien
- 1 Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland.,2 Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, Ireland.,3 Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and TCD, Dublin, Ireland
| |
Collapse
|
|
31
|
Grol MW, Lee BH. Gene therapy for repair and regeneration of bone and cartilage. Curr Opin Pharmacol 2018; 40:59-66. [PMID: 29621661 DOI: 10.1016/j.coph.2018.03.005] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Accepted: 03/12/2018] [Indexed: 12/28/2022]
Abstract
Gene therapy refers to the use of viral and non-viral vectors to deliver nucleic acids to tissues of interest using direct (in vivo) or transduced cell-mediated (ex vivo) approaches. Over the past few decades, strategies have been adopted to express therapeutic transgenes at sites of injury to promote or facilitate repair of bone and cartilage. Targets of interest have typically included secreted proteins such as growth factors and anti-inflammatory mediators; however, work has also begun to focus intracellularly on signaling components, transcription factors and small, regulatory nucleic acids such as microRNAs (miRNAs). In recent years, a number of single therapeutic gene approaches (termed 'monotherapies') have proven effective in preclinical models of disease, and several are being evaluated in clinical trials. In particular, an ex vivo TGF-β1 gene therapy was approved in Korea in 2017 for treatment of moderate-to-severe osteoarthritis (OA). The ability to utilize viral vectors for context-specific and combinatorial gene therapy is also being investigated, and these strategies are likely to be important in more robustly addressing the complexities of tissue repair and regeneration in skeletal disease. In this review, we provide an overview of viral gene therapies being developed for treatment of bone and cartilage pathologies, with an emphasis on emerging combinatorial strategies as well as those targeting intracellular mediators such as miRNAs.
Collapse
Affiliation(s)
- Matthew W Grol
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
| | - Brendan H Lee
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
| |
Collapse
|
|
32
|
Bougioukli S, Sugiyama O, Pannell W, Ortega B, Tan MH, Tang AH, Yoho R, Oakes DA, Lieberman JR. Gene Therapy for Bone Repair Using Human Cells: Superior Osteogenic Potential of Bone Morphogenetic Protein 2-Transduced Mesenchymal Stem Cells Derived from Adipose Tissue Compared to Bone Marrow. Hum Gene Ther 2018; 29:507-519. [PMID: 29212377 DOI: 10.1089/hum.2017.097] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Ex vivo regional gene therapy strategies using animal mesenchymal stem cells genetically modified to overexpress osteoinductive growth factors have been successfully used in a variety of animal models to induce both heterotopic and orthotopic bone formation. However, in order to adapt regional gene therapy for clinical applications, it is essential to assess the osteogenic capacity of transduced human cells and choose the cell type that demonstrates the best clinical potential. Bone-marrow stem cells (BMSC) and adipose-derived stem cells (ASC) were selected in this study for in vitro evaluation, before and after transduction with a lentiviral two-step transcriptional amplification system (TSTA) overexpressing bone morphogenetic protein 2 (BMP-2; LV-TSTA-BMP-2) or green fluorescent protein (GFP; LV-TSTA-GFP). Cell growth, transduction efficiency, BMP-2 production, and osteogenic capacity were assessed. The study demonstrated that BMSC were characterized by a slower cell growth compared to ASC. Fluorescence-activated cell sorting analysis of GFP-transduced cells confirmed successful transduction with the vector and revealed an overall higher but not statistically significant transduction efficiency in ASC versus BMSC (90.2 ± 4.06% vs. 80.4 ± 8.51%, respectively; p = 0.146). Enzyme-linked immunosorbent assay confirmed abundant BMP-2 production by both cell types transduced with LV-TSTA-BMP-2, with BMP-2 production being significantly higher in ASC versus BMSC (239.5 ± 116.55 ng vs. 70.86 ± 24.7 ng; p = 0.001). Quantitative analysis of extracellular deposition of calcium (Alizarin red) and alkaline phosphatase activity showed that BMP-2-transduced cells had a higher osteogenic differentiation capacity compared to non-transduced cells. When comparing the two cell types, ASC/LV-TSTA-BMP-2 demonstrated a significantly higher mineralization potential compared to BMSC/LV-TSTA-BMP-2 7 days post transduction (p = 0.014). In conclusion, this study demonstrates that transduction with LV-TSTA-BMP-2 can significantly enhance the osteogenic potential of both human BMSC and ASC. BMP-2-treated ASC exhibited higher BMP-2 production and greater osteogenic differentiation capacity compared to BMP-2-treated BMSC. These results, along with the fact that liposuction is an easy procedure with lower donor-site morbidity compared to BM aspiration, indicate that adipose tissue might be a preferable source of MSCs to develop a regional gene therapy approach to treat difficult bone-repair scenarios.
Collapse
Affiliation(s)
- Sofia Bougioukli
- 1 Department of Orthopedic Surgery, Keck School of Medicine, University of Southern California , Los Angeles, California
| | - Osamu Sugiyama
- 1 Department of Orthopedic Surgery, Keck School of Medicine, University of Southern California , Los Angeles, California
| | - William Pannell
- 1 Department of Orthopedic Surgery, Keck School of Medicine, University of Southern California , Los Angeles, California
| | - Brandon Ortega
- 1 Department of Orthopedic Surgery, Keck School of Medicine, University of Southern California , Los Angeles, California
| | - Matthew H Tan
- 1 Department of Orthopedic Surgery, Keck School of Medicine, University of Southern California , Los Angeles, California
| | - Amy H Tang
- 1 Department of Orthopedic Surgery, Keck School of Medicine, University of Southern California , Los Angeles, California
| | - Robert Yoho
- 2 Cosmetic Surgery Practice , Pasadena, California
| | - Daniel A Oakes
- 1 Department of Orthopedic Surgery, Keck School of Medicine, University of Southern California , Los Angeles, California
| | - Jay R Lieberman
- 1 Department of Orthopedic Surgery, Keck School of Medicine, University of Southern California , Los Angeles, California
| |
Collapse
|
|
33
|
Grol MW, Stone A, Ruan MZ, Guse K, Lee BH. Prospects of Gene Therapy for Skeletal Diseases. GENETICS OF BONE BIOLOGY AND SKELETAL DISEASE 2018:119-137. [DOI: 10.1016/b978-0-12-804182-6.00008-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
|
34
|
Huang Z, Xu J, Chen J, Chen H, Wang H, Huang Z, Chen Y, Lu X, Lu F, Hu J. Photoacoustic stimulation promotes the osteogenic differentiation of bone mesenchymal stem cells to enhance the repair of bone defect. Sci Rep 2017; 7:15842. [PMID: 29158525 PMCID: PMC5696557 DOI: 10.1038/s41598-017-15879-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 10/30/2017] [Indexed: 02/05/2023] Open
Abstract
The aim of this study was to evaluate the direct photoacoustic (PA) effect on bone marrow mesenchymal stem cells (BMSCs) which is a key cell source for osteogenesis. As scaffold is also an indispensable element for tissue regeneration, here we firstly fabricated a composited sheet using polylactic-co-glycolic acid (PLGA) mixing with graphene oxide (GO). BMSCs were seeded on the PLGA-GO sheets and received PA treatment in vitro for 3, 9 and 15 days, respectively. Then the BMSCs were harvested and subjected to assess alkaline phosphatase (ALP) activity, calcium content and osteopontin (OPN) on 3, 9 and 15 days. For in vivo study, PLGA-GO sheet seeded with BMSCs after in vitro PA stimulation for 9 days were implanted to repair the bone defect established in the femoral mid-shaft of Sprague-Dawley rat. PLGA-GO group with PA pretreatment showed promising outcomes in terms of the expression of ALP, OPN, and calcium content, thus enhanced the repair of bone defect. In conclusion, we have developed an alternative approach to enhance the repair of bone defect by making good use of the beneficial effect of PA.
Collapse
Affiliation(s)
- Zebin Huang
- Department of Orthopaedics, the First Affiliated Hospital, Shantou University Medical College, Guangdong Province, China
| | - Jiankun Xu
- Department of Orthopaedics, the First Affiliated Hospital, Shantou University Medical College, Guangdong Province, China
- Department of Orthopaedics and Traumatology, Prince of Wales Hospital, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jiebin Chen
- Department of Orthopaedics, the First Affiliated Hospital, Shantou University Medical College, Guangdong Province, China
| | - Hongjiang Chen
- Department of Orthopaedics, the First Affiliated Hospital, Shantou University Medical College, Guangdong Province, China
| | - Hailong Wang
- Department of Chemistry and Key Laboratory for Preparation and Application of Ordered Structural Materials of Guangdong Province, Shantou University, Guangdong Province, China
| | - Zhonglian Huang
- Department of Orthopaedics, the First Affiliated Hospital, Shantou University Medical College, Guangdong Province, China
| | - Youbin Chen
- Department of Orthopaedics, the First Affiliated Hospital, Shantou University Medical College, Guangdong Province, China
| | - Xiaolin Lu
- Department of Orthopaedics, the First Affiliated Hospital, Shantou University Medical College, Guangdong Province, China
| | - Fushen Lu
- Department of Chemistry and Key Laboratory for Preparation and Application of Ordered Structural Materials of Guangdong Province, Shantou University, Guangdong Province, China.
| | - Jun Hu
- Department of Orthopaedics, the First Affiliated Hospital, Shantou University Medical College, Guangdong Province, China.
| |
Collapse
|
|
35
|
Abstract
Adipose-derived stem/stromal cells (ASCs), together with adipocytes, vascular endothelial cells, and vascular smooth muscle cells, are contained in fat tissue. ASCs, like the human bone marrow stromal/stem cells (BMSCs), can differentiate into several lineages (adipose cells, fibroblast, chondrocytes, osteoblasts, neuronal cells, endothelial cells, myocytes, and cardiomyocytes). They have also been shown to be immunoprivileged, and genetically stable in long-term cultures. Nevertheless, unlike the BMSCs, ASCs can be easily harvested in large amounts with minimal invasive procedures. The combination of these properties suggests that these cells may be a useful tool in tissue engineering and regenerative medicine.
Collapse
Affiliation(s)
- Simone Ciuffi
- Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
| | - Roberto Zonefrati
- Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
| | - Maria Luisa Brandi
- Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
| |
Collapse
|
|
36
|
Bustos F, Sepúlveda H, Prieto CP, Carrasco M, Díaz L, Palma J, Lattus J, Montecino M, Palma V. Runt-Related Transcription Factor 2 Induction During Differentiation of Wharton's Jelly Mesenchymal Stem Cells to Osteoblasts Is Regulated by Jumonji AT-Rich Interactive Domain 1B Histone Demethylase. Stem Cells 2017; 35:2430-2441. [DOI: 10.1002/stem.2704] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Accepted: 08/26/2017] [Indexed: 12/19/2022]
Affiliation(s)
- Francisco Bustos
- Laboratory of Stem Cells and Development; Faculty of Sciences, Universidad de Chile, Ñuñoa; Santiago Chile
- FONDAP Center for Genome Regulation.; Santiago Chile
- Sir James Black Centre, School of Life Sciences; University of Dundee; Dundee United Kingdom
| | - Hugo Sepúlveda
- FONDAP Center for Genome Regulation.; Santiago Chile
- Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello.; Santiago Chile
| | - Catalina P. Prieto
- Laboratory of Stem Cells and Development; Faculty of Sciences, Universidad de Chile, Ñuñoa; Santiago Chile
- FONDAP Center for Genome Regulation.; Santiago Chile
| | - Margarita Carrasco
- FONDAP Center for Genome Regulation.; Santiago Chile
- Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello.; Santiago Chile
| | - Lorena Díaz
- Laboratory of Stem Cells and Development; Faculty of Sciences, Universidad de Chile, Ñuñoa; Santiago Chile
| | - José Palma
- Laboratory of Stem Cells and Development; Faculty of Sciences, Universidad de Chile, Ñuñoa; Santiago Chile
| | - José Lattus
- Department of Obstetrics and Gynecology; Dr. Luis Tisné Brousse Hospital, Universidad de Chile, Campus Oriente.; Peñalolén Santiago Chile
| | - Martín Montecino
- FONDAP Center for Genome Regulation.; Santiago Chile
- Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello.; Santiago Chile
| | - Verónica Palma
- Laboratory of Stem Cells and Development; Faculty of Sciences, Universidad de Chile, Ñuñoa; Santiago Chile
- FONDAP Center for Genome Regulation.; Santiago Chile
| |
Collapse
|
|
37
|
Yu J, Xu L, Li K, Xie N, Xi Y, Wang Y, Zheng X, Chen X, Wang M, Ye X. Zinc-modified Calcium Silicate Coatings Promote Osteogenic Differentiation through TGF-β/Smad Pathway and Osseointegration in Osteopenic Rabbits. Sci Rep 2017; 7:3440. [PMID: 28611362 PMCID: PMC5469779 DOI: 10.1038/s41598-017-03661-5] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Accepted: 05/03/2017] [Indexed: 12/19/2022] Open
Abstract
Surface-modified metal implants incorporating different ions have been employed in the biomedical field as bioactive dental implants with good osseointegration properties. However, the molecular mechanism through which surface coatings exert the biological activity is not fully understood, and the effects have been difficult to achieve, especially in the osteopenic bone. In this study, We examined the effect of zinc-modified calcium silicate coatings with two different Zn contents to induce osteogenic differentiation of rat bone marrow-derived pericytes (BM-PCs) and osteogenetic efficiency in ovariectomised rabbits. Ti-6Al-4V with zinc-modified calcium silicate coatings not only enhanced proliferation but also promoted osteogenic differentiation and mineralized matrix deposition of rat BM-PCs as the zinc content and culture time increased in vitro. The associated molecular mechanisms were investigated by Q-PCR and Western blotting, revealing that TGF-β/Smad signaling pathway plays a direct and significant role in regulating BM-PCs osteoblastic differentiation on Zn-modified coatings. Furthermore, in vivo results that revealed Zn-modified calcium silicate coatings significantly promoted new bone formation around the implant surface in osteopenic rabbits as the Zn content and exposure time increased. Therefore, Zn-modified calcium silicate coatings can improve implant osseointegration in the condition of osteopenia, which may be beneficial for patients suffering from osteoporosis-related fractures.
Collapse
Affiliation(s)
- Jiangming Yu
- Department of Orthopaedics, Changzheng Hospital of Second Military Medical University, Shanghai, 200003, China.
- National Engineering Research Center for Nanotechnology, Shanghai, 200241, China.
| | - Lizhang Xu
- Department of Orthopaedics, Changzheng Hospital of Second Military Medical University, Shanghai, 200003, China
| | - Kai Li
- Key Laboratory of Inorganic Coating Materials, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China
| | - Ning Xie
- Department of Orthopaedics, Changzheng Hospital of Second Military Medical University, Shanghai, 200003, China
| | - Yanhai Xi
- Department of Orthopaedics, Changzheng Hospital of Second Military Medical University, Shanghai, 200003, China
| | - Yang Wang
- Department of Orthopaedics, Changzheng Hospital of Second Military Medical University, Shanghai, 200003, China
| | - Xuebin Zheng
- Key Laboratory of Inorganic Coating Materials, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China
| | - Xiongsheng Chen
- Department of Orthopaedics, Changzheng Hospital of Second Military Medical University, Shanghai, 200003, China
| | - Meiyan Wang
- Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
| | - Xiaojian Ye
- Department of Orthopaedics, Changzheng Hospital of Second Military Medical University, Shanghai, 200003, China.
| |
Collapse
|
|
38
|
Barba M, Di Taranto G, Lattanzi W. Adipose-derived stem cell therapies for bone regeneration. Expert Opin Biol Ther 2017; 17:677-689. [PMID: 28374644 DOI: 10.1080/14712598.2017.1315403] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Cell-based therapies exploit the heterogeneous and self-sufficient biological environment of stem cells to restore, maintain and improve tissue functions. Adipose-derived stem cells (ASCs) are, to this aim, promising cell types thanks to advantageous isolation procedures, growth kinetics, plasticity and trophic properties. Specifically, bone regeneration represents a suitable, though often challenging, target setting to test and apply ASC-based therapeutic strategies. Areas covered: ASCs are extremely plastic and secrete bioactive peptides that mediate paracrine functions, mediating their trophic actions in vivo. Numerous preclinical studies demonstrated that ASCs improve bone healing. Clinical trials are ongoing to validate the clinical feasibility of these approaches. This review is intended to define the state-of-the-art on ASCs, encompassing the biological features that make them suitable for bone regenerative strategies, and to provide an update on existing preclinical and clinical applications. Expert opinion: ASCs offer numerous advantages over other stem cells in terms of feasibility of clinical translation. Data obtained from in vivo experimentation are encouraging, and clinical trials are ongoing. More robust validations are thus expected to be achieved during the next few years, and will likely pave the way to optimized patient-tailored treatments for bone regeneration.
Collapse
Affiliation(s)
- Marta Barba
- a Institute of Anatomy and Cell Biology , Università Cattolica del Sacro Cuore , Rome , Italy
| | - Giuseppe Di Taranto
- b Department of Plastic, Reconstructive and Aesthetic Surgery , University of Rome "Sapienza" , Policlinico Umberto I, Rome , Italy
| | - Wanda Lattanzi
- a Institute of Anatomy and Cell Biology , Università Cattolica del Sacro Cuore , Rome , Italy
| |
Collapse
|
|
39
|
Tassi SA, Sergio NZ, Misawa MYO, Villar CC. Efficacy of stem cells on periodontal regeneration: Systematic review of pre-clinical studies. J Periodontal Res 2017; 52:793-812. [PMID: 28394043 DOI: 10.1111/jre.12455] [Citation(s) in RCA: 100] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/14/2017] [Indexed: 01/10/2023]
Abstract
This systematic review aims to evaluate mesenchymal stem cells (MSC) periodontal regenerative potential in animal models. MEDLINE, EMBASE and LILACS databases were searched for quantitative pre-clinical controlled animal model studies that evaluated the effect of local administration of MSC on periodontal regeneration. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines. Twenty-two studies met the inclusion criteria. Periodontal defects were surgically created in all studies. In seven studies, periodontal inflammation was experimentally induced following surgical defect creation. Differences in defect morphology were identified among the studies. Autogenous, alogenous and xenogenous MSC were used to promote periodontal regeneration. These included bone marrow-derived MSC, periodontal ligament (PDL)-derived MSC, dental pulp-derived MSC, gingival margin-derived MSC, foreskin-derived induced pluripotent stem cells, adipose tissue-derived MSC, cementum-derived MSC, periapical follicular MSC and alveolar periosteal cells. Meta-analysis was not possible due to heterogeneities in study designs. In most of the studies, local MSC implantation was not associated with adverse effects. The use of bone marrow-derived MSC for periodontal regeneration yielded conflicting results. In contrast, PDL-MSC consistently promoted increased PDL and cementum regeneration. Finally, the adjunct use of MSC improved the regenerative outcomes of periodontal defects treated with membranes or bone substitutes. Despite the quality level of the existing evidence, the current data indicate that the use of MSC may provide beneficial effects on periodontal regeneration. The various degrees of success of MSC in periodontal regeneration are likely to be related to the use of heterogeneous cells. Thus, future studies need to identify phenotypic profiles of highly regenerative MSC populations.
Collapse
Affiliation(s)
- S A Tassi
- Division of Periodontics, Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, Brazil
| | - N Z Sergio
- Division of Periodontics, Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, Brazil
| | - M Y O Misawa
- Division of Periodontics, Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, Brazil
| | - C C Villar
- Division of Periodontics, Department of Stomatology, School of Dentistry, University of São Paulo, São Paulo, Brazil.,Department of Periodontics, University of Texas Health Science Center at San Antonio Dental School, San Antonio, TX, USA
| |
Collapse
|
|
40
|
Sun J, Zhang Y, Li B, Gu Y, Chen L. Controlled release of BMP-2 from a collagen-mimetic peptide-modified silk fibroin–nanohydroxyapatite scaffold for bone regeneration. J Mater Chem B 2017; 5:8770-8779. [PMID: 32264271 DOI: 10.1039/c7tb02043k] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Controlled release of BMP-2 from a collagen-mimetic peptide-modified scaffold for bone regeneration.
Collapse
Affiliation(s)
- Jiachen Sun
- Department of Orthopaedic Surgery
- The First Affiliated Hospital of Soochow University
- Suzhou
- P. R. China
| | - Yanxia Zhang
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science
- Soochow University
- Suzhou
- P. R. China
| | - Bin Li
- Department of Orthopaedic Surgery
- The First Affiliated Hospital of Soochow University
- Suzhou
- P. R. China
- Orthopedic Institute
| | - Yong Gu
- Department of Orthopaedic Surgery
- The First Affiliated Hospital of Soochow University
- Suzhou
- P. R. China
| | - Liang Chen
- Department of Orthopaedic Surgery
- The First Affiliated Hospital of Soochow University
- Suzhou
- P. R. China
| |
Collapse
|
|
41
|
Fu X, Yang H, Zhang H, Wang G, Liu K, Gu Q, Tao Y, Chen G, Jiang X, Li G, Gu Y, Shi Q. Improved osteogenesis and upregulated immunogenicity in human placenta-derived mesenchymal stem cells primed with osteogenic induction medium. Stem Cell Res Ther 2016; 7:138. [PMID: 27649692 PMCID: PMC5028975 DOI: 10.1186/s13287-016-0400-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Revised: 06/18/2016] [Accepted: 08/30/2016] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSCs) are widely used in cell-based therapy owing to their multilineage potential and low immunogenicity. However, low differentiation efficiency and unpredictable immunogenicity of allogeneic MSCs in vivo limit their success in therapeutic treatment. Herein, we evaluated the differentiation potential and immunogenicity of human placenta-derived MSCs manipulated with osteogenic priming and dedifferentiation process. METHODS MSCs from human placentas were subjected to osteogenic induction and then cultivated in osteogenic factor-free media; the obtained cell population was termed dedifferentiated mesenchymal stem cells (De-MSCs). De-MSCs were induced into osteo-, chondro- and adipo-differentiation in vitro. Cell proliferation was quantified by a Cell-Counting Kit-8 or tritiated thymidine ([(3)H]-TdR) incorporation. Meanwhile, the osteogenesis of De-MSCs in vivo was assayed by real-time PCR and histological staining. The expressions of stem cell markers and co-stimulatory molecules on De-MSCs and lymphocytes from primed BALB/c mouse with De-MSCs were determined by flow cytometry. RESULTS De-MSCs exhibited some properties similar to MSCs including multiple differentiation potential and hypoimmunogenicity. Upon re-osteogenic induction, De-MSCs exhibited higher differentiation capability than MSCs both in vitro and in vivo. Of note, De-MSCs had upregulated immunogenicity in association with their osteogenesis, reflected by the alternated expressions of co-stimulatory molecules on the surface and decreased suppression on T cell activation. Functionally, De-MSC-derived osteoblasts could prime lymphocytes of peripheral blood and spleen in BALB/c mice in vivo. CONCLUSIONS These data are of great significance for the potential application of De-MSCs as an alternative resource for regenerative medicine and tissue engineering. In order to avoid being rejected by the host during allogeneic De-MSC therapy, we suggest that immune intervention should be considered to boost the immune acceptance and integration because of the upregulated immunogenicity of De-MSCs with redifferentiation in clinical applications.
Collapse
Affiliation(s)
- Xuejie Fu
- Orthopedic Department, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, 215006, People's Republic of China
| | - Huilin Yang
- Orthopedic Department, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, 215006, People's Republic of China
| | - Hui Zhang
- Orthopedic Department, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, 215006, People's Republic of China
| | - Guichao Wang
- Orthopedic Department, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, 215006, People's Republic of China
| | - Ke Liu
- Orthopedic Department, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, 215006, People's Republic of China
| | - Qiaoli Gu
- Orthopedic Department, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, 215006, People's Republic of China
| | - Yunxia Tao
- Orthopedic Department, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, 215006, People's Republic of China
| | - Guangcun Chen
- Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine and i-Lab, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, People's Republic of China
| | - Xiaohua Jiang
- Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China
| | - Gang Li
- Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, China
| | - Yanzheng Gu
- Orthopedic Department, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, 215006, People's Republic of China. .,Key Laboratory of Stem Cell of Jiangsu Province, Institute of Medical Biotechnology, Soochow University, No.188 Shizi Street, Suzhou, 215006, People's Republic of China.
| | - Qin Shi
- Orthopedic Department, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, Suzhou, 215006, People's Republic of China.
| |
Collapse
|
|
42
|
Bhattacharya I, Ghayor C, Weber FE. The Use of Adipose Tissue-Derived Progenitors in Bone Tissue Engineering - a Review. Transfus Med Hemother 2016; 43:336-343. [PMID: 27781021 DOI: 10.1159/000447494] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Accepted: 06/08/2016] [Indexed: 12/12/2022] Open
Abstract
2500 years ago, Hippocrates realized that bone can heal without scaring. The natural healing potential of bone is, however, restricted to small defects. Extended bone defects caused by trauma or during tumor resections still pose a huge problem in orthopedics and cranio-maxillofacial surgery. Bone tissue engineering strategies using stem cells, growth factors, and scaffolds could overcome the problems with the treatment of extended bone defects. In this review, we give a short overview on bone tissue engineering with emphasis on the use of adipose tissue-derived stem cells and small molecules.
Collapse
Affiliation(s)
- Indranil Bhattacharya
- Oral Biotechnology & Bioengineering, Cranio-Maxillofacial and Oral Surgery, Center for Dental Medicine, University of Zurich, Zurich, Switzerland
| | - Chafik Ghayor
- Oral Biotechnology & Bioengineering, Cranio-Maxillofacial and Oral Surgery, Center for Dental Medicine, University of Zurich, Zurich, Switzerland
| | - Franz E Weber
- Oral Biotechnology & Bioengineering, Cranio-Maxillofacial and Oral Surgery, Center for Dental Medicine, University of Zurich, Zurich, Switzerland
| |
Collapse
|
|
43
|
Histological analysis of in vitro co-culture and in vivo mice co-transplantation of stem cell-derived adipocyte and osteoblast. Tissue Eng Regen Med 2016; 13:227-234. [PMID: 30603403 DOI: 10.1007/s13770-016-9094-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2015] [Revised: 12/23/2015] [Accepted: 12/28/2015] [Indexed: 11/27/2022] Open
Abstract
Many researchers have focused on the role of adipocytes in increasing efficient bone tissue engineering and osteogenic differentiation of stem cells. Previous reports have not reached a definite consensus on whether adipocytes positively influence in vitro osteogenic differentiation and in vivo bone formation. We investigated the adipocyte influence on osteogenic differentiation from adipose-derived stromal cells (ADSCs) and bone formation through histological analysis in vitro and in vivo. Using the direct co-culture system, we analyzed the influence of adipocytes to promote the differentiation fate of ADSCs. Using co-transplantation of ADSC-derived adipocytes and osteoblasts into the dorsal region of mice, the osteogenesis and bone quality were determined by histological morphology, radiography, and the measurement of the Ca2+ concentration. The adipocyte negatively affected the osteoblast differentiation of ADSCs in the in vitro system and induced osteogenesis of osteoblasts in the in vivo system through co-transplantation. Interestingly, in the co-transplanted adipocytes and osteoblasts, the bone formation areas decreased in the osteoblast only group compared with the mixed adipocytes and osteoblast group 6 weeks after transplantation. Conversely, co-transplantation and osteoblast transplantation had similar degrees of calcification as observed from radiography analysis and the measurement of the Ca2+ concentrations. Our results revealed that adipocytes inhibited osteoblast differentiation in vitro but enhanced the efficacy of osteogenesis in vivo. In addition, the adipocytes controlled the activity of osteoclasts in the newly formed bone tissue. Our approach can be used to reconstruct bone using stem cell-based tissue engineering and to enhance the understanding of the role adipocytes play.
Collapse
|
|
44
|
Wang X, Huang J, Wang K, Neufurth M, Schröder HC, Wang S, Müller WE. The morphogenetically active polymer, inorganic polyphosphate complexed with GdCl 3 , as an inducer of hydroxyapatite formation in vitro. Biochem Pharmacol 2016; 102:97-106. [DOI: 10.1016/j.bcp.2015.12.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2015] [Accepted: 12/14/2015] [Indexed: 12/30/2022]
|
|
45
|
Gene delivery of osteoinductive signals to a human fetal osteoblast cell line induces cell death in a dose-dependent manner. Drug Deliv Transl Res 2016; 5:160-7. [PMID: 25787741 DOI: 10.1007/s13346-013-0163-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Gene delivery provides a powerful tool for regulating tissue regeneration by activating or inhibiting specific genes associated with targeted signaling pathways. Up-regulating bone morphogenetic protein-2 (BMP-2) or silencing GNAS and Noggin gene expression in stem cells has been shown to enhance osteogenic differentiation and bone tissue formation. However, few studies have examined how such gene delivery would influence other differentiated cell types residing in the bone. In this study, we examined the effects of DNA delivery of BMP-2 and siRNA delivery of GNAS or Noggin on a widely used human fetal osteoblast cell line (hFOB1.19) using biomaterials-mediated gene delivery. Our results showed that both GNAS and Noggin siRNA delivery increased cell death in hFOB1.19 in a dose-dependent manner. In particular, groups treated with the highest doses of BMP-2, siGNAS or siNoggin showed a more than 50% decline in cell proliferation and a 90% decline in cell viability compared to untransfected and sham DNA/siRNA-transfected controls. TUNEL staining showed that BMP-2, siGNAS or siNoggin induced cell apoptosis in hFOBs. In contrast, cells transfected using sham DNA or siRNA showed no noticeable cell death or apoptosis. These results elucidate the nuanced responses of progenitor and immortalized cell populations to the delivery of exogenous osteoinductive genes. In particular, they highlight the differences between immortalized and primary cell lines and underscore the importance of targeted gene delivery mechanisms in the regeneration of injured bone tissue.
Collapse
|
|
46
|
Kwon D, Kim JS, Cha BH, Park KS, Han I, Park KS, Bae H, Han MK, Kim KS, Lee SH. The Effect of Fetal Bovine Serum (FBS) on Efficacy of Cellular Reprogramming for Induced Pluripotent Stem Cell (iPSC) Generation. Cell Transplant 2015; 25:1025-42. [PMID: 26450367 DOI: 10.3727/096368915x689703] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Induced pluripotent stem cells (iPSCs) are pivotal to the advancement of regenerative medicine. However, the low efficacy of iPSC generation and insufficient knowledge about the reprogramming mechanisms involved in somatic cell/adult stem cell reversion to a pluripotent phenotype remain critical hurdles to the therapeutic application of iPSCs. The present study investigated whether the concentration of fetal bovine serum (FBS), a widely employed cell culture additive, can influence the cellular reprogramming efficacy (RE) of human adipose-derived stem cells (hADSCs) to generate iPSCs. Compared with the typically employed concentration of FBS (10%), high concentrations (20% and 30%) increased the RE of hADSCs by approximately twofold, whereas a low concentration (5%) decreased the RE by the same extent. Furthermore, cell counting kit-8 (CCK-8), bromodeoxyuridine (BrdU) incorporation, and fluorescence-activated cell sorting (FACS) assays showed that hADSC proliferation during reprogramming was significantly enhanced by FBS at 20% and 30%, whereas quantitative polymerase chain reaction (qPCR) and Western blotting assays revealed a concomitant decrease in p53, p51, and p21 expression. In addition, the efficacy of retrovirus-mediated transduction into hADSCs was increased by approximately 10% at high concentrations of FBS. It was confirmed that platelet-derived growth factor in the FBS enhanced proliferation and reprogramming efficacy. Finally, the generated iPSCs showed a normal karyotype, the same fingerprinting pattern as parental hADSCs, a genome-wide transcriptome pattern similar to that of human embryonic stem cells (hESCs), and in vivo pluripotency. In conclusion, the current investigation demonstrated that high concentrations of FBS can modulate molecular and cellular mechanisms underlying the reprogramming process in hADSCs, thereby augmenting the cellular RE for iPSC generation.
Collapse
Affiliation(s)
- Daekee Kwon
- Department of Biomedical Science, College of Life Science, CHA University, Gyeonggi-do, Republic of Korea
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
47
|
Griffin MF, Butler PE, Seifalian AM, Kalaskar DM. Control of stem cell fate by engineering their micro and nanoenvironment. World J Stem Cells 2015; 7:37-50. [PMID: 25621104 PMCID: PMC4300935 DOI: 10.4252/wjsc.v7.i1.37] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2014] [Revised: 09/13/2014] [Accepted: 09/19/2014] [Indexed: 02/06/2023] Open
Abstract
Stem cells are capable of long-term self-renewal and differentiation into specialised cell types, making them an ideal candidate for a cell source for regenerative medicine. The control of stem cell fate has become a major area of interest in the field of regenerative medicine and therapeutic intervention. Conventional methods of chemically inducing stem cells into specific lineages is being challenged by the advances in biomaterial technology, with evidence highlighting that material properties are capable of driving stem cell fate. Materials are being designed to mimic the clues stem cells receive in their in vivo stem cell niche including topographical and chemical instructions. Nanotopographical clues that mimic the extracellular matrix (ECM) in vivo have shown to regulate stem cell differentiation. The delivery of ECM components on biomaterials in the form of short peptides sequences has also proved successful in directing stem cell lineage. Growth factors responsible for controlling stem cell fate in vivo have also been delivered via biomaterials to provide clues to determine stem cell differentiation. An alternative approach to guide stem cells fate is to provide genetic clues including delivering DNA plasmids and small interfering RNAs via scaffolds. This review, aims to provide an overview of the topographical, chemical and molecular clues that biomaterials can provide to guide stem cell fate. The promising features and challenges of such approaches will be highlighted, to provide directions for future advancements in this exciting area of stem cell translation for regenerative medicine.
Collapse
|
|
48
|
Schroeder J, Kueper J, Leon K, Liebergall M. Stem cells for spine surgery. World J Stem Cells 2015; 7:186-194. [PMID: 25621119 PMCID: PMC4300930 DOI: 10.4252/wjsc.v7.i1.186] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2014] [Revised: 10/08/2014] [Accepted: 10/29/2014] [Indexed: 02/06/2023] Open
Abstract
In the past few years, stem cells have become the focus of research by regenerative medicine professionals and tissue engineers. Embryonic stem cells, although capable of differentiating into cell lineages of all three germ layers, are limited in their utilization due to ethical issues. In contrast, the autologous harvest and subsequent transplantation of adult stem cells from bone marrow, adipose tissue or blood have been experimentally utilized in the treatment of a wide variety of diseases ranging from myocardial infarction to Alzheimer’s disease. The physiologic consequences of stem cell transplantation and its impact on functional recovery have been studied in countless animal models and select clinical trials. Unfortunately, the bench to bedside translation of this research has been slow. Nonetheless, stem cell therapy has received the attention of spinal surgeons due to its potential benefits in the treatment of neural damage, muscle trauma, disk degeneration and its potential contribution to bone fusion.
Collapse
|
|
49
|
Fang YL, Chen XG, W T G. Gene delivery in tissue engineering and regenerative medicine. J Biomed Mater Res B Appl Biomater 2014; 103:1679-99. [PMID: 25557560 DOI: 10.1002/jbm.b.33354] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Revised: 11/07/2014] [Accepted: 11/18/2014] [Indexed: 12/13/2022]
Abstract
As a promising strategy to aid or replace tissue/organ transplantation, gene delivery has been used for regenerative medicine applications to create or restore normal function at the cell and tissue levels. Gene delivery has been successfully performed ex vivo and in vivo in these applications. Excellent proliferation capabilities and differentiation potentials render certain cells as excellent candidates for ex vivo gene delivery for regenerative medicine applications, which is why multipotent and pluripotent cells have been intensely studied in this vein. In this review, gene delivery is discussed in detail, along with its applications to tissue engineering and regenerative medicine. A definition of a stem cell is compared to a definition of a stem property, and both provide the foundation for an in-depth look at gene delivery investigations from a germ lineage angle.
Collapse
Affiliation(s)
- Y L Fang
- Department of Chemical & Biomolecular Engineering, Laboratory for Gene Therapy and Cellular Engineering, Tulane University, 300 Lindy Boggs Center, New Orleans, Louisiana, 70118
| | - X G Chen
- Department of Chemical & Biomolecular Engineering, Laboratory for Gene Therapy and Cellular Engineering, Tulane University, 300 Lindy Boggs Center, New Orleans, Louisiana, 70118
| | - Godbey W T
- Department of Chemical & Biomolecular Engineering, Laboratory for Gene Therapy and Cellular Engineering, Tulane University, 300 Lindy Boggs Center, New Orleans, Louisiana, 70118
| |
Collapse
|
|
50
|
Lin CY, Chang YH, Sung LY, Chen CL, Lin SY, Li KC, Yen TC, Lin KJ, Hu YC. Long-term tracking of segmental bone healing mediated by genetically engineered adipose-derived stem cells: focuses on bone remodeling and potential side effects. Tissue Eng Part A 2014; 20:1392-402. [PMID: 24367947 DOI: 10.1089/ten.tea.2013.0314] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
We previously showed that transplantation of adipose-derived stem cells (ASCs) engineered with hybrid baculovirus (BV) persistently expressing bone morphogenetic protein 2 (BMP2)/vascular endothelial growth factor (VEGF) into segmental defects in New Zealand White (NZW) rabbits led to successful defect reunion. By using microcomputed tomography and histology, here we further demonstrated that transplanting the hybrid BV-engineered ASCs into the massive defects (10 mm in length) at the femoral diaphysis of NZW rabbits resulted in trabecular bone formation in the interior via endochondral ossification and bone remodeling at 3 months post-transplantation. The progression of bone remodeling gave rise to the resorption of trabecular bone and conspicuous reconstruction of medullary cavity and cortical bone with lamellar structure at 8 months post-transplantation, hence conferring mechanical properties that were comparable to those of nonoperated femora. Importantly, X-ray, positron emission tomography/computed tomography scans, and histopathology revealed no signs of heterotopic bone formation and tumor formation. These data altogether attested that the genetically engineered ASCs and prolonged BMP2/VEGF expression not only healed and remodeled the stringent segmental defects, but also revitalized the defects into living bone tissues that structurally and biomechanically resembled intact bones without appreciable side effects, making it one step closer to translate this technology to the clinical setting.
Collapse
Affiliation(s)
- Chin-Yu Lin
- 1 Department of Chemical Engineering, National Tsing Hua University , Hsinchu, Taiwan
| | | | | | | | | | | | | | | | | |
Collapse
|