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Lecoutre S, Rebière C, Maqdasy S, Lambert M, Dussaud S, Abatan JB, Dugail I, Gautier EL, Clément K, Marcelin G. Enhancing adipose tissue plasticity: progenitor cell roles in metabolic health. Nat Rev Endocrinol 2025; 21:272-288. [PMID: 39757324 DOI: 10.1038/s41574-024-01071-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/27/2024] [Indexed: 01/07/2025]
Abstract
Adipose tissue demonstrates considerable plasticity and heterogeneity, enabling metabolic, cellular and structural adaptations to environmental signals. This adaptability is key for maintaining metabolic homeostasis. Impaired adipose tissue plasticity can lead to abnormal adipose tissue responses to metabolic cues, which contributes to the development of cardiometabolic diseases. In chronic obesity, white adipose tissue undergoes pathological remodelling marked by adipocyte hypertrophy, chronic inflammation and fibrosis, which are linked to local and systemic insulin resistance. Research data suggest that the capacity for healthy or unhealthy white adipose tissue remodelling might depend on the intrinsic diversity of adipose progenitor cells (APCs), which sense and respond to metabolic cues. This Review highlights studies on APCs as key determinants of adipose tissue plasticity, discussing differences between subcutaneous and visceral adipose tissue depots during development, growth and obesity. Modulating APC functions could improve strategies for treating adipose tissue dysfunction and metabolic diseases in obesity.
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Affiliation(s)
- Simon Lecoutre
- Nutrition and Obesities: Systemic Approach Research Group, Nutriomics, Sorbonne Université, INSERM, Paris, France.
| | - Clémentine Rebière
- Nutrition and Obesities: Systemic Approach Research Group, Nutriomics, Sorbonne Université, INSERM, Paris, France
| | - Salwan Maqdasy
- Department of Medicine, Karolinska Institutet Hospital, Stockholm, Sweden
| | - Mélanie Lambert
- Institut National de la Santé et de la Recherche Médicale, Bobigny, France
- Labex Inflamex, Université Sorbonne Paris Nord, Alliance Sorbonne Paris Cité, Bobigny, France
| | - Sébastien Dussaud
- Nutrition and Obesities: Systemic Approach Research Group, Nutriomics, Sorbonne Université, INSERM, Paris, France
| | - Jimon Boniface Abatan
- Nutrition and Obesities: Systemic Approach Research Group, Nutriomics, Sorbonne Université, INSERM, Paris, France
| | - Isabelle Dugail
- Nutrition and Obesities: Systemic Approach Research Group, Nutriomics, Sorbonne Université, INSERM, Paris, France
| | - Emmanuel L Gautier
- Nutrition and Obesities: Systemic Approach Research Group, Nutriomics, Sorbonne Université, INSERM, Paris, France
| | - Karine Clément
- Nutrition and Obesities: Systemic Approach Research Group, Nutriomics, Sorbonne Université, INSERM, Paris, France.
- Department of Nutrition, Pitie-Salpêtriere Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
| | - Geneviève Marcelin
- Nutrition and Obesities: Systemic Approach Research Group, Nutriomics, Sorbonne Université, INSERM, Paris, France.
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Zielinska D, Micka-Michalak K, Ademi H, Fisch P, Boeni R, Linder T, Moehrlen U, Biedermann T, Klar AS. Adipose-mesenchymal stem cells enhance the formation of auricular cartilage in vitro and in vivo. Stem Cells Transl Med 2025; 14:szae098. [PMID: 40304399 PMCID: PMC12042163 DOI: 10.1093/stcltm/szae098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Accepted: 10/11/2024] [Indexed: 05/02/2025] Open
Abstract
Patients suffering from microtia have limited treatment options for auricular reconstruction due to donor-site morbidity, complications, and unaesthetic outcome. Therefore, tissue engineering emerged as an alternative therapeutic option. Here, we generated and characterized human auricular cartilage using differentiated human adipose mesenchymal stem cells (hASCs) combined with human auricular chondrocytes. The differentiated hASCs were analysed for their morphology, phenotype, gene, and protein expression of chondrogenic markers, and biochemical composition at different time points in 2D and 3D in vitro. Importantly, we improved conditions for chondrogenic differentiation of hASCs in vitro to enhance their proliferation, survival, and deposition of cartilaginous-matrix proteins. In particular, gene expression analysis revealed an upregulation of cartilage oligomeric matrix protein (COMP) and aggrecan core protein (ACAN) in hASCs using the improved differentiation protocol in vitro. Additionally, we observed that co-seeding of hASCs with chondrocytes in a 1:5 ratio significantly enhanced the de novo auricular cartilage formation in a collagen-I bioink after 8 weeks on immunodeficient rat. In particular, the co-culture resulted in reduced shrinkage, and increased cartilage matrix production as confirmed by GAG deposition in vivo. Our results demonstrate that in co-cultures, hASCs stimulate cartilage formation due to a synergistic effect: hASCs' differentiation into chondrocytes and a trophic effect of hASCs on human auricular chondrocytes. Here we demonstrate the successful use of an hASC-chondrocyte co-culture technique for auricular cartilage tissue engineering in 3D collagen-I bioink. This co-culture approach omits the major drawbacks of traditional cartilage transplantation and thus, represents a fundamental step towards clinical translation.
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Affiliation(s)
- Dominika Zielinska
- Tissue Biology Research Unit, Department of Surgery, University Children’s Hospital Zurich, University of Zurich, 8952 Schlieren, Switzerland
- Medical Faculty, University of Zurich, 8006 Zurich, Switzerland
- Children’s Research Center, University Children’s Hospital Zurich, 8008 Zurich, Switzerland
| | - Katarzyna Micka-Michalak
- Tissue Biology Research Unit, Department of Surgery, University Children’s Hospital Zurich, University of Zurich, 8952 Schlieren, Switzerland
- Medical Faculty, University of Zurich, 8006 Zurich, Switzerland
- Children’s Research Center, University Children’s Hospital Zurich, 8008 Zurich, Switzerland
| | - Hyrije Ademi
- Tissue Biology Research Unit, Department of Surgery, University Children’s Hospital Zurich, University of Zurich, 8952 Schlieren, Switzerland
- Medical Faculty, University of Zurich, 8006 Zurich, Switzerland
- Children’s Research Center, University Children’s Hospital Zurich, 8008 Zurich, Switzerland
| | - Philip Fisch
- Tissue Engineering and Biofabrication Laboratory, Department of Health Sciences and Technology, ETH Zurich, 8093 Zurich, Switzerland
| | - Roland Boeni
- White House Centre for Liposuction, 8044 Zurich, Switzerland
| | - Thomas Linder
- Otorhinolaryngology Clinic, Cantonal Hospital Luzern, 6000 Luzern, Switzerland
| | - Ueli Moehrlen
- Tissue Biology Research Unit, Department of Surgery, University Children’s Hospital Zurich, University of Zurich, 8952 Schlieren, Switzerland
- Medical Faculty, University of Zurich, 8006 Zurich, Switzerland
- Children’s Research Center, University Children’s Hospital Zurich, 8008 Zurich, Switzerland
- Department of Pediatric Surgery, University Children’s Hospital Zurich, University of Zurich, 8008 Zurich, Switzerland
| | - Thomas Biedermann
- Tissue Biology Research Unit, Department of Surgery, University Children’s Hospital Zurich, University of Zurich, 8952 Schlieren, Switzerland
- Medical Faculty, University of Zurich, 8006 Zurich, Switzerland
- Children’s Research Center, University Children’s Hospital Zurich, 8008 Zurich, Switzerland
| | - Agnes S Klar
- Tissue Biology Research Unit, Department of Surgery, University Children’s Hospital Zurich, University of Zurich, 8952 Schlieren, Switzerland
- Medical Faculty, University of Zurich, 8006 Zurich, Switzerland
- Children’s Research Center, University Children’s Hospital Zurich, 8008 Zurich, Switzerland
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Jenkins TL, Venkataraman S, Saleh A, Calve S, Pourdeyhimi B, Little D. Application of Tendon-Derived Matrix and Carbodiimide Crosslinking Matures the Engineered Tendon-Like Proteome on Meltblown Scaffolds. J Tissue Eng Regen Med 2025; 2025:2184723. [PMID: 40224957 PMCID: PMC11985250 DOI: 10.1155/term/2184723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 01/20/2025] [Indexed: 04/15/2025]
Abstract
Background: Tendon injuries are increasingly common and heal by fibrosis rather than scar-less regeneration. Tissue engineering seeks to improve repair using synthetic polymer scaffolds with biomimetic factors to enhance the regenerative potential. Methods: In this study, we compared three groups, namely, poly(lactic acid) (PLA) meltblown scaffolds, PLA meltblown scaffolds coated with tendon-derived matrix (TDM), and PLA meltblown scaffolds with carbodiimide crosslinked TDM (2.5:1:1 EDC:NHS:COOH ratio) (EDC-TDM) and determined their potential for engineered tendon development. We cultured human adipose stem cells (hASCs) for 28 days on meltblown scaffolds (n = 4-6/group) and measured tensile mechanical function, matrix synthesis, and matrix composition using biochemical assays and proteomics. Results: Coating PLA meltblown scaffolds with TDM improved yield stretch and stress at 28 days compared with PLA. Matrix synthesis rates for TDM or EDC-TDM were similar to PLA. Proteomic analysis revealed that hASCs produced a collagen-rich extracellular matrix, with many tendon-related matrix proteins. Coating scaffolds with TDM led to an increase in collagen type I whereas EDC-TDM scaffolds had an increase in glycoproteins and ECM regulators compared with other groups, consistent with increased maturity of the newly deposited matrix. Conclusions: TDM coating and crosslinking of meltblown scaffolds demonstrated matricellular benefits for the proteome of engineered tendon development but provided fewer clear benefits toward mechanical, biochemical, and rate of matrix accumulation than expected, and that previous work with electrospun scaffolds would suggest. However, electrospun scaffolds have different fiber structure and microarchitecture than meltblown, suggesting that further consideration of these differences and refinement of TDM application methods to meltblown scaffolds is required.
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Affiliation(s)
- Thomas Lee Jenkins
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA
| | - Sadhana Venkataraman
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA
| | - Aya Saleh
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA
| | - Sarah Calve
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA
- Department of Mechanical Engineering, University of Colorado-Boulder, Boulder, Colorado, USA
| | - Behnam Pourdeyhimi
- The Nonwovens Institute, North Carolina State University, Raleigh, North Carolina, USA
| | - Dianne Little
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA
- Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA
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4
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Tivig I, Vallet L, Moisescu MG, Fernandes R, Andre FM, Mir LM, Savopol T. Early differentiation of mesenchymal stem cells is reflected in their dielectrophoretic behavior. Sci Rep 2024; 14:4330. [PMID: 38383752 PMCID: PMC10881469 DOI: 10.1038/s41598-024-54350-z] [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: 12/13/2023] [Accepted: 02/12/2024] [Indexed: 02/23/2024] Open
Abstract
The therapeutic use of mesenchymal stem cells (MSCs) becomes more and more important due to their potential for cell replacement procedures as well as due to their immunomodulatory properties. However, protocols for MSCs differentiation can be lengthy and may result in incomplete or asynchronous differentiation. To ensure homogeneous populations for therapeutic purposes, it is crucial to develop protocols for separation of the different cell types after differentiation. In this article we show that, when MSCs start to differentiate towards adipogenic or osteogenic progenies, their dielectrophoretic behavior changes. The values of cell electric parameters which can be obtained by dielectrophoretic measurements (membrane permittivity, conductivity, and cytoplasm conductivity) change before the morphological features of differentiation become microscopically visible. We further demonstrate, by simulation, that these electric modifications make possible to separate cells in their early stages of differentiation by using the dielectrophoretic separation technique. A label free method which allows obtaining cultures of homogenously differentiated cells is thus offered.
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Grants
- PN-III-P2-2.1-PED-2021, grant no. 596PED/2022 Romanian Executive Agency for Higher Education, Research, Development, and Innovation Funding
- PN-III-P2-2.1-PED-2021, grant no. 596PED/2022 Romanian Executive Agency for Higher Education, Research, Development, and Innovation Funding
- PN-III-P2-2.1-PED-2021, grant no. 596PED/2022 Romanian Executive Agency for Higher Education, Research, Development, and Innovation Funding
- PN-III-P3-3.1-PM-RO-FR-2019, grant no. 11BM/2019 Romania-France cooperation program Hubert Curien-Brancusi
- PN-III-P3-3.1-PM-RO-FR-2019, grant no. 11BM/2019 Romania-France cooperation program Hubert Curien-Brancusi
- PN-III-P3-3.1-PM-RO-FR-2019, grant no. 11BM/2019 Romania-France cooperation program Hubert Curien-Brancusi
- PN-III-P3-3.1-PM-RO-FR-2019, grant no. 11BM/2019 Romania-France cooperation program Hubert Curien-Brancusi
- FET-OPEN H2020, grant no. 964562 Horizon 2020
- FET-OPEN H2020, grant no. 964562 Horizon 2020
- FET-OPEN H2020, grant no. 964562 Horizon 2020
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Affiliation(s)
- Ioan Tivig
- Biophysics and Cellular Biotechnology Department, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd., 050474, Bucharest, Romania
- Excellence Center for Research in Biophysics and Cellular Biotechnology, Carol Davila University of Medicine and Pharmacy, 050474, Bucharest, Romania
| | - Leslie Vallet
- METSY UMR 9018, Université Paris-Saclay, CNRS and Gustave Roussy, 94805, Villejuif, France
| | - Mihaela G Moisescu
- Biophysics and Cellular Biotechnology Department, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd., 050474, Bucharest, Romania.
- Excellence Center for Research in Biophysics and Cellular Biotechnology, Carol Davila University of Medicine and Pharmacy, 050474, Bucharest, Romania.
| | - Romain Fernandes
- METSY UMR 9018, Université Paris-Saclay, CNRS and Gustave Roussy, 94805, Villejuif, France
| | - Franck M Andre
- METSY UMR 9018, Université Paris-Saclay, CNRS and Gustave Roussy, 94805, Villejuif, France
| | - Lluis M Mir
- METSY UMR 9018, Université Paris-Saclay, CNRS and Gustave Roussy, 94805, Villejuif, France
| | - Tudor Savopol
- Biophysics and Cellular Biotechnology Department, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd., 050474, Bucharest, Romania
- Excellence Center for Research in Biophysics and Cellular Biotechnology, Carol Davila University of Medicine and Pharmacy, 050474, Bucharest, Romania
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Dey MK, Devireddy RV. Adult Stem Cells Freezing Processes and Cryopreservation Protocols. Methods Mol Biol 2024; 2783:53-89. [PMID: 38478226 DOI: 10.1007/978-1-0716-3762-3_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/26/2024]
Abstract
The development of simple but effective storage protocols for adult stem cells will greatly enhance their use and utility in tissue-engineering applications. Cryopreservation has shown the most promise but is a fairly complex process, necessitating the use of chemicals called cryoprotective agents (CPAs), freezing equipment, and obviously, storage in liquid nitrogen. The purpose of this chapter is to present a general overview of cryopreservation storage techniques and the optimal protocols/results obtained in our laboratory for long-term storage of adult stem cells using freezing storage.
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Affiliation(s)
- Mohan Kumar Dey
- Bioengineering Laboratory, Department of Mechanical Engineering, Louisiana State University, Baton Rouge, LA, USA
| | - Ram V Devireddy
- Bioengineering Laboratory, Department of Mechanical Engineering, Louisiana State University, Baton Rouge, LA, USA.
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6
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Li J, Wu Z, Zhao L, Liu Y, Su Y, Gong X, Liu F, Zhang L. The heterogeneity of mesenchymal stem cells: an important issue to be addressed in cell therapy. Stem Cell Res Ther 2023; 14:381. [PMID: 38124129 PMCID: PMC10734083 DOI: 10.1186/s13287-023-03587-y] [Citation(s) in RCA: 54] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 11/24/2023] [Indexed: 12/23/2023] Open
Abstract
With the continuous improvement of human technology, the medical field has gradually moved from molecular therapy to cellular therapy. As a safe and effective therapeutic tool, cell therapy has successfully created a research boom in the modern medical field. Mesenchymal stem cells (MSCs) are derived from early mesoderm and have high self-renewal and multidirectional differentiation ability, and have become one of the important cores of cell therapy research by virtue of their immunomodulatory and tissue repair capabilities. In recent years, the application of MSCs in various diseases has received widespread attention, but there are still various problems in the treatment of MSCs, among which the heterogeneity of MSCs may be one of the causes of the problem. In this paper, we review the correlation of MSCs heterogeneity to provide a basis for further reduction of MSCs heterogeneity and standardization of MSCs and hope to provide a reference for cell therapy.
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Affiliation(s)
- Jingxuan Li
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Zewen Wu
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Li Zhao
- School of Pharmacy, Shanxi Medical University, Taiyuan, 030600, China
| | - Yang Liu
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Yazhen Su
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Xueyan Gong
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Fancheng Liu
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China
| | - Liyun Zhang
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China.
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7
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Camera F, Colantoni E, Garcia-Sanchez T, Benassi B, Consales C, Muscat A, Vallet L, Mir LM, Andre F, Merla C. In Vitro Imaging and Molecular Characterization of Ca 2+ Flux Modulation by Nanosecond Pulsed Electric Fields. Int J Mol Sci 2023; 24:15616. [PMID: 37958601 PMCID: PMC10647260 DOI: 10.3390/ijms242115616] [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: 09/06/2023] [Revised: 10/18/2023] [Accepted: 10/23/2023] [Indexed: 11/15/2023] Open
Abstract
In recent years, the application of pulsed electric fields with very short durations (nanoseconds) and extremely high amplitudes (MV/m) has been investigated for novel medical purposes. Various electric protocols have been explored for different objectives, including the utilization of fractionated pulse doses to enhance cell electrosensitization to the uptake of different markers or an increase in apoptosis. This study focused on the use of fluorescence imaging to examine molecular calcium fluxes induced by different fractionated protocols of short electric pulses in neuroblastoma (SH-SY5Y) and mesenchymal stem cells (HaMSCs) that were electroporated using nanosecond pulsed electric fields. In our experimental setup, we did not observe cell electrosensitization in terms of an increase in calcium flux following the administration of fractionated doses of nanosecond pulsed electric fields with respect to the non-fractionated dose. However, we observed the targeted activation of calcium-dependent genes (c-FOS, c-JUN, EGR1, NURR-1, β3-TUBULIN) based on the duration of calcium flux, independent of the instantaneous levels achieved but solely dependent on the final plateau reached. This level of control may have potential applications in various medical and biological treatments that rely on calcium and the delivery of nanosecond pulsed electric fields.
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Affiliation(s)
- Francesca Camera
- Division of Health Protection Technologies, Italian National Agency for Energy, New Technologies and Sustainable Economic Development (ENEA), 00123 Rome, Italy; (F.C.); (E.C.); (B.B.); (C.C.)
| | - Eleonora Colantoni
- Division of Health Protection Technologies, Italian National Agency for Energy, New Technologies and Sustainable Economic Development (ENEA), 00123 Rome, Italy; (F.C.); (E.C.); (B.B.); (C.C.)
| | - Tomas Garcia-Sanchez
- Department of Information and Communication Technologies, Pompeu Fabra University, 08002 Barcelona, Spain;
| | - Barbara Benassi
- Division of Health Protection Technologies, Italian National Agency for Energy, New Technologies and Sustainable Economic Development (ENEA), 00123 Rome, Italy; (F.C.); (E.C.); (B.B.); (C.C.)
| | - Claudia Consales
- Division of Health Protection Technologies, Italian National Agency for Energy, New Technologies and Sustainable Economic Development (ENEA), 00123 Rome, Italy; (F.C.); (E.C.); (B.B.); (C.C.)
| | - Adeline Muscat
- CNRS, Metabolic and Systemic Aspects of the Oncogenesis, (METSY), Institute Gustave Roussy, Paris-Saclay University, 94805 Villejuif, France; (A.M.); (L.V.); (L.M.M.); (F.A.)
| | - Leslie Vallet
- CNRS, Metabolic and Systemic Aspects of the Oncogenesis, (METSY), Institute Gustave Roussy, Paris-Saclay University, 94805 Villejuif, France; (A.M.); (L.V.); (L.M.M.); (F.A.)
| | - Luis M. Mir
- CNRS, Metabolic and Systemic Aspects of the Oncogenesis, (METSY), Institute Gustave Roussy, Paris-Saclay University, 94805 Villejuif, France; (A.M.); (L.V.); (L.M.M.); (F.A.)
| | - Franck Andre
- CNRS, Metabolic and Systemic Aspects of the Oncogenesis, (METSY), Institute Gustave Roussy, Paris-Saclay University, 94805 Villejuif, France; (A.M.); (L.V.); (L.M.M.); (F.A.)
| | - Caterina Merla
- Division of Health Protection Technologies, Italian National Agency for Energy, New Technologies and Sustainable Economic Development (ENEA), 00123 Rome, Italy; (F.C.); (E.C.); (B.B.); (C.C.)
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8
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Wan Y, Hu C, Hou Y, Si C, Zhao Q, Wang Z, Wang L, Guo X. OPG gene-modified adipose-derived stem cells improve bone formation around implants in osteoporotic rat maxillae. Heliyon 2023; 9:e19474. [PMID: 37817994 PMCID: PMC10560787 DOI: 10.1016/j.heliyon.2023.e19474] [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: 04/25/2023] [Revised: 08/14/2023] [Accepted: 08/23/2023] [Indexed: 10/12/2023] Open
Abstract
Background Osteoporosis is a significant barrier to the use of dental implants in the elderly for the treatment of tooth defects. Adipose derived stem cells (ADSCs) have demonstrated extensive potential for tissue repair and regeneration. The present study aimed to investigate the effectiveness of ADSCs engineered to express high levels of osteoprotegerin (OPG) for the treatment of bone loss in implant dentistry caused by estrogen deficiency. Methods A rat model of osteoporosis was established through double oophorectomy, and the rats were treated by gene modified cells Adv-OPG-ADSCs. The effects of the treatment on maxilla tissue changes were evaluated using HE staining and micro-CT. Additionally, ALP and TRAP staining were used to assess osteoblast and osteoclast alterations. Finally, the changes in related osteoblast and osteoclast indicators were measured by RT-qPCR, Western blot, and ELISA. Results The successfully generated high-OPG-expressing ADSCs led to increase of cell viability, proliferation, and osteoblast differentiation. Treatment with Adv-OPG-ADSCs significantly ameliorated maxillary morphology, trabecular volume reduction, and bone mineral density decline in the model of estrogen-deficient maxillary implant dentistry. Furthermore, the treatment was beneficial to promoting the generation of osteoblasts and inhibiting the generation of osteoclast. Adv-OPG-ADSCs increased OPG, ALP, OCN, and Runx-2 expressions in the maxilla while suppressing RANKL expression, and also increased the concentration of COL I and PINP, as well as decreased the concentration of CTX-1. Conclusion Adv-OPG-ADSCs promote the formation of osteoblasts and inhibit the generation of osteoclasts, thereby inhibiting bone absorption, facilitating bone formation, and promoting the repair of maxillary bone after dental implantation in the presence of osteoporosis-related complications, especially in the setting of estrogen deficiency, providing scientific basis for the application of Adv-OPG-ADSCs in the treatment of implant related osteoporosis.
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Affiliation(s)
| | | | - Yongjie Hou
- General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Chenchen Si
- General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Qian Zhao
- General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Zhenzhen Wang
- General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Liyuan Wang
- General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, China
| | - Xiaoqian Guo
- General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, China
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9
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He S, Deng H, Li P, Hu J, Yang Y, Xu Z, Liu S, Guo W, Guo Q. Arthritic Microenvironment-Dictated Fate Decisions for Stem Cells in Cartilage Repair. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2207715. [PMID: 37518822 PMCID: PMC10520688 DOI: 10.1002/advs.202207715] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 06/05/2023] [Indexed: 08/01/2023]
Abstract
The microenvironment and stem cell fate guidance of post-traumatic articular cartilage regeneration is primarily the focus of cartilage tissue engineering. In articular cartilage, stem cells are characterized by overlapping lineages and uneven effectiveness. Within the first 12 weeks after trauma, the articular inflammatory microenvironment (AIME) plays a decisive role in determining the fate of stem cells and cartilage. The development of fibrocartilage and osteophyte hyperplasia is an adverse outcome of chronic inflammation, which results from an imbalance in the AIME during the cartilage tissue repair process. In this review, the sources for the different types of stem cells and their fate are summarized. The main pathophysiological events that occur within the AIME as well as their protagonists are also discussed. Additionally, regulatory strategies that may guide the fate of stem cells within the AIME are proposed. Finally, strategies that provide insight into AIME pathophysiology are discussed and the design of new materials that match the post-traumatic progress of AIME pathophysiology in a spatial and temporal manner is guided. Thus, by regulating an appropriately modified inflammatory microenvironment, efficient stem cell-mediated tissue repair may be achieved.
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Affiliation(s)
- Songlin He
- School of MedicineNankai UniversityTianjin300071China
- Institute of Orthopedicsthe First Medical CenterChinese PLA General HospitalBeijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma & War Injuries PLABeijing100853China
| | - Haotian Deng
- School of MedicineNankai UniversityTianjin300071China
- Institute of Orthopedicsthe First Medical CenterChinese PLA General HospitalBeijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma & War Injuries PLABeijing100853China
| | - Peiqi Li
- School of MedicineNankai UniversityTianjin300071China
- Institute of Orthopedicsthe First Medical CenterChinese PLA General HospitalBeijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma & War Injuries PLABeijing100853China
| | - Jingjing Hu
- Department of GastroenterologyInstitute of GeriatricsChinese PLA General HospitalBeijing100853China
| | - Yongkang Yang
- Institute of Orthopedicsthe First Medical CenterChinese PLA General HospitalBeijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma & War Injuries PLABeijing100853China
| | - Ziheng Xu
- Institute of Orthopedicsthe First Medical CenterChinese PLA General HospitalBeijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma & War Injuries PLABeijing100853China
| | - Shuyun Liu
- School of MedicineNankai UniversityTianjin300071China
- Institute of Orthopedicsthe First Medical CenterChinese PLA General HospitalBeijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma & War Injuries PLABeijing100853China
| | - Weimin Guo
- Department of Orthopaedic SurgeryGuangdong Provincial Key Laboratory of Orthopedics and TraumatologyFirst Affiliated HospitalSun Yat‐Sen UniversityGuangzhouGuangdong510080China
| | - Quanyi Guo
- School of MedicineNankai UniversityTianjin300071China
- Institute of Orthopedicsthe First Medical CenterChinese PLA General HospitalBeijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma & War Injuries PLABeijing100853China
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10
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Gianakos AL, Kennedy JG. Rethinking Cartilage Lesions of the Ankle: An Update on the Role of Biologic Adjuvants. J Am Acad Orthop Surg 2023; 31:701-707. [PMID: 37026780 DOI: 10.5435/jaaos-d-22-01042] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 03/03/2023] [Indexed: 04/08/2023] Open
Abstract
Osteochondral lesions of the talus are common injuries in the ankle joint often resulting in early-onset osteoarthritis if left untreated. The avascular nature of articular cartilage limits healing capacity; therefore, surgical strategies are typically used in the treatment of these injuries. These treatments often result in the production of fibrocartilage rather than the native hyaline cartilage, which has decreased mechanical and tribological properties. Strategies to improve the ability of fibrocartilage to be more hyaline-like and thus more mechanically robust have been widely investigated. Biologic augmentation, including concentrated bone marrow aspirate, platelet-rich plasma, hyaluronic acid, and micronized adipose tissue, has been used in the augmentation of cartilage healing, with studies demonstrating promise. This article provides an overview and update on the various biologic adjuvants used in the treatment of cartilage injuries in the ankle joint.
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Affiliation(s)
- Arianna L Gianakos
- From the Department of Orthopaedic Surgery, NYU Langone Health, New York, NY (Gianakos and Kennedy), and the Department of Orthopaedic Surgery, Yale Medicine, Orthopaedics, and Rehabilitation, New Haven, CT (Gianakos)
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11
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Petrova V, Vachkova E. Outlook of Adipose-Derived Stem Cells: Challenges to Their Clinical Application in Horses. Vet Sci 2023; 10:vetsci10050348. [PMID: 37235430 DOI: 10.3390/vetsci10050348] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 05/05/2023] [Accepted: 05/11/2023] [Indexed: 05/28/2023] Open
Abstract
Adipose tissue is recognized as the major endocrine organ, potentially acting as a source of mesenchymal stem cells for various applications in regenerative medicine. Athletic horses are often exposed to traumatic injuries, resulting in severe financial losses. The development of adipose-derived stem cells' regenerative potential depends on many factors. The extraction of stem cells from subcutaneous adipose tissue is non-invasive, non-traumatic, cheaper, and safer than other sources. Since there is a lack of unique standards for identification, the isolated cells and applied differentiation protocols are often not species-specific; therefore, the cells cannot reveal their multipotent properties, so their stemness features remain questionable. The current review discusses some aspects of the specificity of equine adipose stem cells concerning their features, immunophenotyping, secretome profile, differentiation abilities, culturing conditions, and consequent possibilities for clinical application in concrete disorders. The presented new approaches elucidate the possibility of the transition from cell-based to cell-free therapy with regenerative purposes in horses as an alternative treatment to cellular therapy. In conclusion, their clinical benefits should not be underestimated due to the higher yield and the physiological properties of adipose-derived stem cells that facilitate the healing and tissue regeneration process and the ability to amplify the effects of traditional treatments. More profound studies are necessary to apply these innovative approaches when treating traumatic disorders in racing horses.
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Affiliation(s)
- Valeria Petrova
- Department of Pharmacology, Animal Physiology and Physiological Chemistry, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
| | - Ekaterina Vachkova
- Department of Pharmacology, Animal Physiology and Physiological Chemistry, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria
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12
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Gutierrez RA, Fonseca VC, Darling EM. Chondrogenesis of Adipose-Derived Stem Cells Using an Arrayed Spheroid Format. Cell Mol Bioeng 2022; 15:587-597. [PMID: 36531862 PMCID: PMC9751248 DOI: 10.1007/s12195-022-00746-8] [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: 07/14/2022] [Accepted: 10/08/2022] [Indexed: 11/03/2022] Open
Abstract
Objective The chondrogenic response of adipose-derived stem cells (ASCs) is often assessed using 3D micromass protocols that use upwards of hundreds of thousands of cells. Scaling these systems up for high-throughput testing is technically challenging and wasteful given the necessary cell numbers and reagent volumes. However, adopting microscale spheroid cultures for this purpose shows promise. Spheroid systems work with only thousands of cells and microliters of medium. Methods Molded agarose microwells were fabricated using 2% w/v molten agarose and then equilibrated in medium prior to introducing cells. ASCs were seeded at 50, 500, 5k cells/microwell; 5k, 50k, cells/well plate; and 50k and 250k cells/15 mL centrifuge tube to compare chondrogenic responses across spheroid and micromass sizes. Cells were cultured in control or chondrogenic induction media. ASCs coalesced into spheroids/pellets and were cultured at 37 °C and 5% CO2 for 21 days with media changes every other day. Results All culture conditions supported growth of ASCs and formation of viable cell spheroids/micromasses. More robust growth was observed in chondrogenic conditions. Sulfated glycosaminoglycans and collagen II, molecules characteristics of chondrogenesis, were prevalent in both 5000-cell spheroids and 250,000-cell micromasses. Deposition of collagen I, characteristic of fibrocartilage, was more prevalent in the large micromasses than small spheroids. Conclusions Chondrogenic differentiation was consistently induced using high-throughput spheroid formats, particularly when seeding at cell densities of 5000 cells/spheroid. This opens possibilities for highly arrayed experiments investigating tissue repair and remodeling during or after exposure to drugs, toxins, or other chemicals. Supplementary Information The online version contains supplementary material available at 10.1007/s12195-022-00746-8.
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Affiliation(s)
- Robert A. Gutierrez
- Center for Biomedical Engineering, Brown University, Box G-B397, Providence, RI 02912 USA
| | - Vera C. Fonseca
- Department of Pathology and Laboratory Medicine, Providence, USA
| | - Eric M. Darling
- Center for Biomedical Engineering, Brown University, Box G-B397, Providence, RI 02912 USA
- Department of Pathology and Laboratory Medicine, Providence, USA
- School of Engineering, Brown University, Providence, USA
- Department of Orthopaedics, Brown University, Providence, USA
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13
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Hatzmann FM, Großmann S, Waldegger P, Wiegers GJ, Mandl M, Rauchenwald T, Pierer G, Zwerschke W. Dipeptidyl peptidase-4 cell surface expression marks an abundant adipose stem/progenitor cell population with high stemness in human white adipose tissue. Adipocyte 2022; 11:601-615. [PMID: 36168895 PMCID: PMC9542856 DOI: 10.1080/21623945.2022.2129060] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
The capacity of adipose stem/progenitor cells (ASCs) to undergo self-renewal and differentiation is crucial for adipose tissue homoeostasis, regeneration and expansion. However, the heterogeneous ASC populations of the adipose lineage constituting adipose tissue are not precisely known. In the present study, we demonstrate that cell surface expression of dipeptidyl peptidase-4 (DPP4)/cluster of differentiation 26 (CD26) subdivides the DLK1-/CD34+/CD45-/CD31- ASC pool of human white adipose tissues (WATs) into two large populations. Ex vivo, DPP4+ ASCs possess higher self-renewal and proliferation capacity and lesser adipocyte differentiation potential than DDP4- ASCs. The knock-down of DPP4 in ASC leads to significantly reduced proliferation and self-renewal capacity, while adipogenic differentiation is increased. Ectopic overexpression of DPP4 strongly inhibits adipogenesis. Moreover, in whole mount stainings of human subcutaneous (s)WAT, we detect DPP4 in CD34+ ASC located in the vascular stroma surrounding small blood vessels and in mature adipocytes. We conclude that DPP4 is a functional marker for an abundant ASC population in human WAT with high proliferation and self-renewal potential and low adipogenic differentiation capacity.
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Affiliation(s)
- Florian M Hatzmann
- Division of Cell Metabolism and Differentiation Research, Research Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria,Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria
| | - Sonja Großmann
- Division of Cell Metabolism and Differentiation Research, Research Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria,Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria
| | - Petra Waldegger
- Division of Cell Metabolism and Differentiation Research, Research Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria,Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria
| | - G Jan Wiegers
- Division of Developmental Immunology, Biocenter, Medical University Innsbruck, Innsbruck, Austria
| | - Markus Mandl
- Division of Cell Metabolism and Differentiation Research, Research Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria,Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria
| | - Tina Rauchenwald
- Department of Plastic and Reconstructive Surgery, Innsbruck Medical University, Innsbruck, Austria
| | - Gerhard Pierer
- Department of Plastic and Reconstructive Surgery, Innsbruck Medical University, Innsbruck, Austria
| | - Werner Zwerschke
- Division of Cell Metabolism and Differentiation Research, Research Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria,Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria,CONTACT Werner Zwerschke Head of the Division of Cell Metabolism and Differentiation Research, Research Institute for Biomedical Aging Research, University of Innsbruck
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14
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Kurenkova AD, Romanova IA, Kibirskiy PD, Timashev P, Medvedeva EV. Strategies to Convert Cells into Hyaline Cartilage: Magic Spells for Adult Stem Cells. Int J Mol Sci 2022; 23:11169. [PMID: 36232468 PMCID: PMC9570095 DOI: 10.3390/ijms231911169] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 09/17/2022] [Accepted: 09/19/2022] [Indexed: 11/30/2022] Open
Abstract
Damaged hyaline cartilage gradually decreases joint function and growing pain significantly reduces the quality of a patient's life. The clinically approved procedure of autologous chondrocyte implantation (ACI) for treating knee cartilage lesions has several limits, including the absence of healthy articular cartilage tissues for cell isolation and difficulties related to the chondrocyte expansion in vitro. Today, various ACI modifications are being developed using autologous chondrocytes from alternative sources, such as the auricles, nose and ribs. Adult stem cells from different tissues are also of great interest due to their less traumatic material extraction and their innate abilities of active proliferation and chondrogenic differentiation. According to the different adult stem cell types and their origin, various strategies have been proposed for stem cell expansion and initiation of their chondrogenic differentiation. The current review presents the diversity in developing applied techniques based on autologous adult stem cell differentiation to hyaline cartilage tissue and targeted to articular cartilage damage therapy.
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Affiliation(s)
- Anastasiia D. Kurenkova
- Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia or
| | - Irina A. Romanova
- World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
| | - Pavel D. Kibirskiy
- Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia or
| | - Peter Timashev
- Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia or
- World-Class Research Center “Digital Biodesign and Personalized Healthcare”, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
| | - Ekaterina V. Medvedeva
- Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia or
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15
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Yu J, Hsu YC, Lee JK, Cheng NC. Enhanced angiogenic potential of adipose-derived stem cell sheets by integration with cell spheroids of the same source. Stem Cell Res Ther 2022; 13:276. [PMID: 35765015 PMCID: PMC9241243 DOI: 10.1186/s13287-022-02948-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Accepted: 06/09/2022] [Indexed: 11/24/2022] Open
Abstract
Background Adipose-derived stem cell (ASC) has been considered as a desirable source for cell therapy. In contrast to combining scaffold materials with cells, ASCs can be fabricated into scaffold-free three-dimensional (3D) constructs to promote regeneration at tissue level. However, previous reports have found decreased expression of vascular endothelial growth factor (VEGF) in ASC sheets. In this study, we aimed to integrate ASC spheroids into ASC sheets to enhance the angiogenic capability of cell sheets. Methods ASCs were seeded in agarose microwells to generate uniform cell spheroids with adjustable size, while extracellular matrix deposition could be stimulated by ascorbic acid 2-phosphate to form ASC sheets. RNA sequencing was performed to identify the transcriptomic profiles of ASC spheroids and sheets relative to monolayer ASCs. By transferring ASC spheroids onto ASC sheets, the spheroid sheet composites could be successfully fabricated after a short-term co-culture, and their angiogenic potential was evaluated in vitro and in ovo. Results RNA sequencing analysis revealed that upregulation of angiogenesis-related genes was found only in ASC spheroids. The stimulating effect of spheroid formation on ASCs toward endothelial lineage was demonstrated by enhanced CD31 expression, which maintained after ASC spheroids were seeded on cell sheets. Relative to ASC sheets, enhanced expression of VEGF and hepatocyte growth factor was also noted in ASC spheroid sheets, and conditioned medium of ASC spheroid sheets significantly enhanced tube formation of endothelial cells in vitro. Moreover, chick embryo chorioallantoic membrane assay showed a significantly higher capillary density with more branch points after applying ASC spheroid sheets, and immunohistochemistry also revealed a significantly higher ratio of CD31-positive area. Conclusion In the spheroid sheet construct, ASC spheroids can augment the pro-angiogenesis capability of ASC sheets without the use of exogenous biomaterial or genetic manipulation. The strategy of this composite system holds promise as an advance in 3D culture technique of ASCs for future application in angiogenesis and regeneration therapies. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-02948-3.
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Affiliation(s)
- Jiashing Yu
- Department of Chemical Engineering, College of Engineering, National Taiwan University, 1 Sec. 4, Roosevelt Rd., Taipei 106, Taiwan
| | - Yi-Chiung Hsu
- Department of Biomedical Sciences and Engineering, National Central University, 300 Zhongda Rd., Taoyuan 320, Taiwan
| | - Jen-Kuang Lee
- Department of Medicine, National Taiwan University Hospital and College of Medicine, 7 Chung-Shan S. Rd., Taipei 100, Taiwan
| | - Nai-Chen Cheng
- Department of Surgery, National Taiwan University Hospital and College of Medicine, 7 Chung-Shan S. Rd., Taipei 100, Taiwan.
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16
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Dempsey ME, Chickering GR, González-Cruz RD, Fonseca VC, Darling EM. Discovery of surface biomarkers for cell mechanophenotype via an intracellular protein-based enrichment strategy. Cell Mol Life Sci 2022; 79:320. [PMID: 35622146 PMCID: PMC9239330 DOI: 10.1007/s00018-022-04351-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 04/28/2022] [Accepted: 05/05/2022] [Indexed: 11/03/2022]
Abstract
Cellular mechanophenotype is often a defining characteristic of conditions like cancer malignancy/metastasis, cardiovascular disease, lung and liver fibrosis, and stem cell differentiation. However, acquiring living cells based on mechanophenotype is challenging for conventional cell sorters due to a lack of biomarkers. In this study, we demonstrate a workflow for surface protein discovery associated with cellular mechanophenotype. We sorted heterogeneous adipose-derived stem/stromal cells (ASCs) into groups with low vs. high lamin A/C, an intracellular protein linked to whole-cell mechanophenotype. Proteomic data of enriched groups identified surface protein candidates as potential biochemical proxies for ASC mechanophenotype. Select surface biomarkers were used for live-cell enrichment, with subsequent single-cell mechanical testing and lineage-specific differentiation. Ultimately, we identified CD44 to have a strong inverse correlation with whole-cell elastic modulus, with CD44lo cells exhibiting moduli three times greater than that of CD44hi cells. Functionally, these stiff and soft ASCs showed enhanced osteogenic and adipogenic differentiation potential, respectively. The described workflow can be replicated for any phenotype with a known correlated intracellular protein, allowing for the acquisition of live cells for further characterization, diagnostics, or therapeutics.
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Affiliation(s)
- Megan E Dempsey
- Center for Biomedical Engineering, Brown University, Providence, RI, 02912, USA
| | | | | | - Vera C Fonseca
- Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, 02912, USA
| | - Eric M Darling
- Center for Biomedical Engineering, Brown University, Providence, RI, 02912, USA.
- Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, 02912, USA.
- School of Engineering, Brown University, Providence, RI, 02912, USA.
- Department of Orthopaedics, Brown University, Providence, RI, 02912, USA.
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17
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Cartilage Formation In Vivo Using High Concentration Collagen-Based Bioink with MSC and Decellularized ECM Granules. Int J Mol Sci 2022; 23:ijms23052703. [PMID: 35269850 PMCID: PMC8910854 DOI: 10.3390/ijms23052703] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 02/24/2022] [Accepted: 02/25/2022] [Indexed: 12/12/2022] Open
Abstract
The aim of this study was to verify the applicability of high-concentration collagen-based bioink with MSC (ADSC) and decellularized ECM granules for the formation of cartilage tissue de novo after subcutaneous implantation of the scaffolds in rats. The printability of the bioink (4% collagen, 2.5% decellularized ECM granules, derived via 280 μm sieve) was shown. Three collagen-based compositions were studied: (1) with ECM; (2) with MSC; (3) with ECM and MSC. It has been established that decellularized ECM granules are able to stimulate chondrogenesis both in cell-free and MSC-laden scaffolds. Undesirable effects have been identified: bone formation as well as cartilage formation outside of the scaffold area. The key perspectives and limitations of ECM granules (powder) application have been discussed.
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18
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Zhang Z, Zhang M, Zhang Z, Sun Y, Wang J, Chang C, Zhu X, Li M, Liu Y. ADSCs Combined with Melatonin Promote Peripheral Nerve Regeneration through Autophagy. Int J Endocrinol 2022; 2022:5861553. [PMID: 35910940 PMCID: PMC9329031 DOI: 10.1155/2022/5861553] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 05/02/2022] [Accepted: 06/14/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND In the early stage of nerve injury, damaged tissue is cleared by autophagy. ADSCs can promote nerve axon regeneration. However, the microenvironment of the injury was changed, and ADSCs are easily apoptotic after transplantation. Mel plays a role in the apoptosis, proliferation, and differentiation of ADSCs. Therefore, we investigated whether Mel combined with ADSCs promoted peripheral nerve regeneration by enhancing early autophagy of injured nerves. MATERIALS AND METHODS SD rats were randomly split into the control group, model group, Mel group, ADSCs group, ADSCs + Mel group, and 3-MA group. On day 7, autophagy was observed and gait was detected on days 7, 14, 21, and 28. On the 28th day, the sciatic nerve of rats' renewal was detected. RESULTS After 1 w, compare with the model group, the number of autophagosomes and lysosomes and the expressions of protein of LC3-II/LC3-I and Beclin-1 in the ADSCs + Mel group were prominently increased, while the 3-MA group was significantly decreased. After 4 w, the function of the sciatic nerve in ADSCs + Mel was similar to that in the control group. Compared with the model group, the ADSCs + Mel group significantly increased myelin regeneration and the number of motor neurons and reduced gastrocnemius atrophy. CONCLUSIONS It was confirmed that ADSCs combined with Mel could promote sciatic nerve regeneration in rats by changing the early autophagy activity of the injured sciatic nerve.
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Affiliation(s)
- Ziqiang Zhang
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China
| | - Mengyu Zhang
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China
| | - Zhixiang Zhang
- College of Life Science, Yangtze University, Jingzhou, Hubei 434023, China
| | - Yingying Sun
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China
| | - Jiajia Wang
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China
| | - Chenhao Chang
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China
| | - Xinyan Zhu
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China
| | - Monan Li
- School of Materials Science and Engineering, Henan University of Science and Technology, Luoyang, Henan 471000, China
| | - Yumei Liu
- College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China
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19
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Sundaravadivelu PK, Raina K, Thool M, Ray A, Joshi JM, Kaveeshwar V, Sudhagar S, Lenka N, Thummer RP. Tissue-Restricted Stem Cells as Starting Cell Source for Efficient Generation of Pluripotent Stem Cells: An Overview. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1376:151-180. [PMID: 34611861 DOI: 10.1007/5584_2021_660] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Induced pluripotent stem cells (iPSCs) have vast biomedical potential concerning disease modeling, drug screening and discovery, cell therapy, tissue engineering, and understanding organismal development. In the year 2006, a groundbreaking study reported the generation of iPSCs from mouse embryonic fibroblasts by viral transduction of four transcription factors, namely, Oct4, Sox2, Klf4, and c-Myc. Subsequently, human iPSCs were generated by reprogramming fibroblasts as a starting cell source using two reprogramming factor cocktails [(i) OCT4, SOX2, KLF4, and c-MYC, and (ii) OCT4, SOX2, NANOG, and LIN28]. The wide range of applications of these human iPSCs in research, therapeutics, and personalized medicine has driven the scientific community to optimize and understand this reprogramming process to achieve quality iPSCs with higher efficiency and faster kinetics. One of the essential criteria to address this is by identifying an ideal cell source in which pluripotency can be induced efficiently to give rise to high-quality iPSCs. Therefore, various cell types have been studied for their ability to generate iPSCs efficiently. Cell sources that can be easily reverted to a pluripotent state are tissue-restricted stem cells present in the fetus and adult tissues. Tissue-restricted stem cells can be isolated from fetal, cord blood, bone marrow, and other adult tissues or can be obtained by differentiation of embryonic stem cells or trans-differentiation of other tissue-restricted stem cells. Since these cells are undifferentiated cells with self-renewal potential, they are much easier to reprogram due to the inherent characteristic of having an endogenous expression of few pluripotency-inducing factors. This review presents an overview of promising tissue-restricted stem cells that can be isolated from different sources, namely, neural stem cells, hematopoietic stem cells, mesenchymal stem cells, limbal epithelial stem cells, and spermatogonial stem cells, and their reprogramming efficacy. This insight will pave the way for developing safe and efficient reprogramming strategies and generating patient-specific iPSCs from tissue-restricted stem cells derived from various fetal and adult tissues.
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Affiliation(s)
- Pradeep Kumar Sundaravadivelu
- Laboratory for Stem Cell Engineering and Regenerative Medicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India
| | - Khyati Raina
- Laboratory for Stem Cell Engineering and Regenerative Medicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India
| | - Madhuri Thool
- Laboratory for Stem Cell Engineering and Regenerative Medicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India.,Department of Biotechnology, National Institute of Pharmaceutical Education and Research Guwahati, Changsari, Guwahati, Assam, India
| | - Arnab Ray
- Laboratory for Stem Cell Engineering and Regenerative Medicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India
| | - Jahnavy Madhukar Joshi
- Central Research Laboratory, SDM College of Medical Sciences and Hospital, Shri Dharmasthala Manjunatheshwara University, Dharwad, Karnataka, India
| | - Vishwas Kaveeshwar
- Central Research Laboratory, SDM College of Medical Sciences and Hospital, Shri Dharmasthala Manjunatheshwara University, Dharwad, Karnataka, India
| | - S Sudhagar
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research Guwahati, Changsari, Guwahati, Assam, India
| | - Nibedita Lenka
- National Centre for Cell Science, S. P. Pune University Campus, Ganeshkhind, Pune, Maharashtra, India.
| | - Rajkumar P Thummer
- Laboratory for Stem Cell Engineering and Regenerative Medicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India.
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20
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The Efficacy of Schwann-Like Differentiated Muscle-Derived Stem Cells in Treating Rodent Upper Extremity Peripheral Nerve Injury. Plast Reconstr Surg 2021; 148:787-798. [PMID: 34550935 DOI: 10.1097/prs.0000000000008383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND There is a pressing need to identify alternative mesenchymal stem cell sources for Schwann cell cellular replacement therapy, to improve peripheral nerve regeneration. This study assessed the efficacy of Schwann cell-like cells (induced muscle-derived stem cells) differentiated from muscle-derived stem cells (MDSCs) in augmenting nerve regeneration and improving muscle function after nerve trauma. METHODS The Schwann cell-like nature of induced MDSCs was characterized in vitro using immunofluorescence, flow cytometry, microarray, and reverse-transcription polymerase chain reaction. In vivo, four groups (n = 5 per group) of rats with median nerve injuries were examined: group 1 animals were treated with intraneural phosphate-buffered saline after cold and crush axonotmesis (negative control); group 2 animals were no-injury controls; group 3 animals were treated with intraneural green fluorescent protein-positive MDSCs; and group 4 animals were treated with green fluorescent protein-positive induced MDSCs. All animals underwent weekly upper extremity functional testing. Rats were euthanized 5 weeks after treatment. The median nerve and extrinsic finger flexors were harvested for nerve histomorphometry, myelination, muscle weight, and atrophy analyses. RESULTS In vitro, induced MDSCs recapitulated native Schwann cell gene expression patterns and up-regulated pathways involved in neuronal growth/signaling. In vivo, green fluorescent protein-positive induced MDSCs remained stably transformed 5 weeks after injection. Induced MDSC therapy decreased muscle atrophy after median nerve injury (p = 0.0143). Induced MDSC- and MDSC-treated animals demonstrated greater functional muscle recovery when compared to untreated controls (hand grip after induced MDSC treatment: group 1, 0.91 N; group 4, 3.38 N); p < 0.0001) at 5 weeks after treatment. This may demonstrate the potential beneficial effects of MDSC therapy, regardless of differentiation stage. CONCLUSION Both MDSCs and induced MDSCs decrease denervation muscle atrophy and improve subsequent functional outcomes after upper extremity nerve trauma in rodents.
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21
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Bagheri-Mohammadi S. Stem cell-based therapy as a promising approach in Alzheimer's disease: current perspectives on novel treatment. Cell Tissue Bank 2021; 22:339-353. [PMID: 33398492 DOI: 10.1007/s10561-020-09896-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 12/19/2020] [Indexed: 12/12/2022]
Abstract
Alzheimer's disease (AD) is a neuronal disorder with insidious onset and slow progression, leading to growing global concern with huge implications for individuals and society. The occurrence of AD has been increased and has become an important health issue throughout the world. In recent years, the care of more than 35 million patients with AD costs over $ 600 billion per year, it is approximately 1 percent of the global Gross Domestic Product. Currently, the therapeutic approach is not effective for neurological deficits especially after the development of these major neurological disorders. The discovery of the technique called cell-based therapy has shown promising results and made important conclusions beyond AD using the stem cells approach. Here we review recent progress on stem cell-based therapy in the context of AD.
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Affiliation(s)
- Saeid Bagheri-Mohammadi
- Department of Physiology and Neurophysiology Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Department of Physiology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
- Department of Applied Cell Sciences, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, Iran.
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22
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Ming Y, Liu ZP. Overexpression of lncRNA-NEF regulates the miR-155/PTEN axis to inhibit adipogenesis and promote osteogenesis. Kaohsiung J Med Sci 2021; 37:930-939. [PMID: 34382731 DOI: 10.1002/kjm2.12423] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 06/11/2021] [Accepted: 06/24/2021] [Indexed: 11/10/2022] Open
Abstract
Osteoporosis is characterized by osteopenia and bone tissue microstructure degradation. Adipose-derived stem cells (ADSCs) are multipotent adult stem cells that have the ability to yield mesenchymal stem cells and have the potential to undergo osteogenesis and bone regeneration. Therefore, ADSCs have the potential to treat osteoporosis, but the molecular mechanism of these cells in the process of osteogenesis and osteoclasts is still not clear. In the present study, we collected serum samples from 10 clinical osteoporosis patients to detect long noncoding RNA-neighboring enhancer of FOXA2 (lncRNA-NEF) and miR-155 expression levels. Half of these patients were senile and half were postmenopausal women, and nine of them have used steroids for a long time, in which ADSCs were cultured and induced to adipogenic and osteogenic differentiations. Quantitative real-time polymerase chain reaction was used to detect the expression of genes in ADSCs. Overexpression of lncRNA-NEF in ADSCs were undertaken to verify its regulatory function on cell osteogenic and adipogenic differentiations. A luciferase activity experiment was performed to determine the relationship between miR-155 and phosphatase and tensin homologue deleted on chromosome 10 (PTEN). The level of lncRNA-NEF was downregulated, and miR-155 was upregulated, in serum samples from patients with clinical osteoporosis. LncRNA-NEF showed different expression levels in the induction of osteogenic or adipogenic differentiation, which increased during osteogenic induction and decreased during adipogenic induction. Overexpression of lncRNA-NEF or downregulation of miR-155 in ADSCs promoted osteogenic differentiation and inhibited adipogenesis progression. PTEN was the direct target of miR-155 and was involved in the regulation of osteogenic differentiation. Overexpression of lncRNA-NEF regulated the miR-155/PTEN axis to inhibit adipogenesis and promote osteogenesis in ADSCs.
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Affiliation(s)
- Ying Ming
- Department of Clinical Laboratory, Affiliated Hospital of Chengde Medical University, Chengde, Hebei Province, China
| | - Zheng-Peng Liu
- Department of Spinal Surgery Ward, Affiliated Hospital of Chengde Medical University, Chengde, Hebei Province, China
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23
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Wang Z, Zheng J, Pan R, Chen Y. Current status and future prospects of patient-derived induced pluripotent stem cells. Hum Cell 2021; 34:1601-1616. [PMID: 34378170 DOI: 10.1007/s13577-021-00592-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 08/06/2021] [Indexed: 12/28/2022]
Abstract
Induced pluripotent stem cells (iPSCs) are produced from adult somatic cells through reprogramming, which behave like embryonic stem cells (ESCs) but avoiding the controversial ethical issues from destruction of embryos. Since the first discovery in 2006 of four factors that are essential for maintaining the basic characteristics of ESC, global researches have rapidly improved the techniques for generating iPSCs. In this paper, we review new insights into patient-specific iPSC and summarize selected "disease-in-a-dish" examples that model the genetic and epigenetic variations of human diseases. Although more researches need to be done, studies have increasingly focused on the potential utility of iPSCs. The usability of iPSC technology is changing the fields of disease modeling and precision treatment. Aside from its potential use in regenerative cellular therapy for degenerative diseases, iPSC offers a range of new opportunities for the study of genetic human disorders, particularly, rare diseases. We believe that this rapidly moving field promises many more developments that will benefit modern medicine.
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Affiliation(s)
- Zhiqiang Wang
- Division of Medical Genetics and Genomics, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang, China.,Department of Genetics, Institute of Genetics, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, Zhejiang, China
| | - Jing Zheng
- Division of Medical Genetics and Genomics, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang, China.,Zhejiang Provincial Key Laboratory of Genetic and Developmental Disorders, Hangzhou, 310058, Zhejiang, China
| | - Ruolang Pan
- Institute for Cell-Based Drug Development of Zhejiang Province, S-Evans Biosciences, Hangzhou, 310012, Zhejiang, China.,Key Laboratory of Cell-Based Drug and Applied Technology Development in Zhejiang Province, Hangzhou, 310012, Zhejiang, China
| | - Ye Chen
- Division of Medical Genetics and Genomics, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang, China. .,Department of Genetics, Institute of Genetics, School of Medicine, Zhejiang University, 866 Yuhangtang Road, Hangzhou, 310058, Zhejiang, China. .,Zhejiang Provincial Key Laboratory of Genetic and Developmental Disorders, Hangzhou, 310058, Zhejiang, China.
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Hu T, Zhang H, Yu W, Yu X, Li Z, He L. The Combination of Concentrated Growth Factor and Adipose-Derived Stem Cell Sheet Repairs Skull Defects in Rats. Tissue Eng Regen Med 2021; 18:905-913. [PMID: 34302696 DOI: 10.1007/s13770-021-00371-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 06/23/2021] [Accepted: 06/24/2021] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND The goal of this study was to create a biomaterial which combines concentrated growth factor (CGF) with an adipose-derived stem cell (ADSC) sheet to promote the repair of skull defects in rats. METHODS We determined the optimal concentration of CGF extract by investigating the effects of different concentrations (0, 5%, 10%, and 20%) on the proliferation and differentiation of ADSCs. Then we created a complex combining CGF with an ADSC sheet, and tested the effects on bone repair in four experimental rat groups: (A) control; (B) ADSC sheet; (C) CGF particles; (D) combination of CGF + ADSCs. Eight weeks after the procedure, osteogenesis was assessed by micro-CT and hematoxylin and eosin staining. RESULTS We found that the concentration of CGF extract that promoted optimal ADSC proliferation and differentiation in vitro was 20%. In turn, bone regeneration was promoted the most by the combination of CGF and ADSCs. CONCLUSION In this study, we determined the optimal ratio of CGF and ADSCs to be used in a biomaterial for bone regeneration. The resulting CGF/ADSCs complex promotes maxillofacial bone defect repair in rats.
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Affiliation(s)
- Tuqiang Hu
- Department of Stomatology, Renmin Hospital, Hubei University of Medicine, NO.39 Chaoyang Middle Road, Maojian District, Shiyan, 442000, Hubei, China
| | - Hao Zhang
- Department of Stomatology, Renmin Hospital, Hubei University of Medicine, NO.39 Chaoyang Middle Road, Maojian District, Shiyan, 442000, Hubei, China.,School of Dentistry, Hubei University of Medicine, NO.30 Renmin South Road, Maojian District, Shiyan, 442000, Hubei, China
| | - Wei Yu
- Department of Stomatology, Renmin Hospital, Hubei University of Medicine, NO.39 Chaoyang Middle Road, Maojian District, Shiyan, 442000, Hubei, China
| | - Xuezhou Yu
- Department of Stomatology, Renmin Hospital, Hubei University of Medicine, NO.39 Chaoyang Middle Road, Maojian District, Shiyan, 442000, Hubei, China
| | - Zubing Li
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, NO.237 Luoyu Road, Hongshan District, Wuhan, 430079, Hubei, China
| | - Li He
- Department of Stomatology, Renmin Hospital, Hubei University of Medicine, NO.39 Chaoyang Middle Road, Maojian District, Shiyan, 442000, Hubei, China.
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25
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Ong WK, Chakraborty S, Sugii S. Adipose Tissue: Understanding the Heterogeneity of Stem Cells for Regenerative Medicine. Biomolecules 2021; 11:biom11070918. [PMID: 34206204 PMCID: PMC8301750 DOI: 10.3390/biom11070918] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 06/17/2021] [Accepted: 06/17/2021] [Indexed: 12/13/2022] Open
Abstract
Adipose-derived stem cells (ASCs) have been increasingly used as a versatile source of mesenchymal stem cells (MSCs) for diverse clinical investigations. However, their applications often become complicated due to heterogeneity arising from various factors. Cellular heterogeneity can occur due to: (i) nomenclature and criteria for definition; (ii) adipose tissue depots (e.g., subcutaneous fat, visceral fat) from which ASCs are isolated; (iii) donor and inter-subject variation (age, body mass index, gender, and disease state); (iv) species difference; and (v) study design (in vivo versus in vitro) and tools used (e.g., antibody isolation and culture conditions). There are also actual differences in resident cell types that exhibit ASC/MSC characteristics. Multilineage-differentiating stress-enduring (Muse) cells and dedifferentiated fat (DFAT) cells have been reported as an alternative or derivative source of ASCs for application in regenerative medicine. In this review, we discuss these factors that contribute to the heterogeneity of human ASCs in detail, and what should be taken into consideration for overcoming challenges associated with such heterogeneity in the clinical use of ASCs. Attempts to understand, define, and standardize cellular heterogeneity are important in supporting therapeutic strategies and regulatory considerations for the use of ASCs.
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Affiliation(s)
- Wee Kiat Ong
- School of Pharmacy, Monash University Malaysia, Subang Jaya 47500, Selangor, Malaysia
- Correspondence: (W.K.O.); (S.S.)
| | - Smarajit Chakraborty
- Institute of Bioengineering and Bioimaging (IBB), A*STAR, 31 Biopolis Way, Singapore 138669, Singapore;
| | - Shigeki Sugii
- Institute of Bioengineering and Bioimaging (IBB), A*STAR, 31 Biopolis Way, Singapore 138669, Singapore;
- Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore
- Correspondence: (W.K.O.); (S.S.)
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26
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Role of Fzd6 in Regulating the Osteogenic Differentiation of Adipose-derived Stem Cells in Osteoporotic Mice. Stem Cell Rev Rep 2021; 17:1889-1904. [PMID: 34041696 DOI: 10.1007/s12015-021-10182-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/07/2021] [Indexed: 01/10/2023]
Abstract
OBJECTIVE Although it has been demonstrated that adipose-derived stem cells (ASCs) from osteoporotic mice (OP-ASCs) exhibited impaired osteogenic differentiation potential, the molecular mechanism has not yet been elucidated. We found that Fzd6 was decreased in OP-ASCs compared with ASCs. This study investigates effects and underlying mechanisms of Fzd6 in the osteogenic potential of OP-ASCs, and explores methods to enhance osteogenic capacity of OP-ASCs. METHODS Fzd6 overexpression and silencing lentiviruses were used to evaluate the role of Fzd6 in the osteogenic differentiation of OP-ASCs. Real-time PCR (qPCR) and western blotting (WB) was performed to detect the expression of Fzd6 and bone-related molecules, including runt-related transcription factor 2 (Runx2) and osteopontin (Opn). Alizarin red staining and Alkaline phosphatase (ALP) staining were performed following osteogenic induction. Microscopic CT (Micro-CT), hematoxylin and eosin staining (HE) staining, and Masson staining were used to assess the role of Fzd6 in osteogenic differentiation of osteoporosis (OP) mice in vivo. RESULTS Expression of Fzd6 was decreased significantly in OP-ASCs. Fzd6 silencing down-regulated the osteogenic ability of OP-ASCs in vitro. Overexpression of Fzd6 rescued the impaired osteogenic capacity in OP-ASCs in vitro. We obtained similar results in vivo. CONCLUSIONS Fzd6 plays an important role in regulating the osteogenic ability of OP-ASCs both in vivo and in vitro. Overexpression of Fzd6 promotes the osteogenic ability of OP-ASCs, which provides new insights for the prevention and treatment of OP mice.
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Mende W, Götzl R, Kubo Y, Pufe T, Ruhl T, Beier JP. The Role of Adipose Stem Cells in Bone Regeneration and Bone Tissue Engineering. Cells 2021; 10:cells10050975. [PMID: 33919377 PMCID: PMC8143357 DOI: 10.3390/cells10050975] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 04/19/2021] [Accepted: 04/20/2021] [Indexed: 02/07/2023] Open
Abstract
Bone regeneration is a complex process that is influenced by tissue interactions, inflammatory responses, and progenitor cells. Diseases, lifestyle, or multiple trauma can disturb fracture healing, which might result in prolonged healing duration or even failure. The current gold standard therapy in these cases are bone grafts. However, they are associated with several disadvantages, e.g., donor site morbidity and availability of appropriate material. Bone tissue engineering has been proposed as a promising alternative. The success of bone-tissue engineering depends on the administered cells, osteogenic differentiation, and secretome. Different stem cell types offer advantages and drawbacks in this field, while adipose-derived stem or stromal cells (ASCs) are in particular promising. They show high osteogenic potential, osteoinductive ability, and immunomodulation properties. Furthermore, they can be harvested through a noninvasive process in high numbers. ASCs can be induced into osteogenic lineage through bioactive molecules, i.e., growth factors and cytokines. Moreover, their secretome, in particular extracellular vesicles, has been linked to fracture healing. The aim of this review is a comprehensive overview of ASCs for bone regeneration and bone tissue engineering.
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Affiliation(s)
- Wolfgang Mende
- Hand Surgery-Burn Center, Department of Plastic Surgery, RWTH Aachen University Hospital, 52074 Aachen, Germany
| | - Rebekka Götzl
- Hand Surgery-Burn Center, Department of Plastic Surgery, RWTH Aachen University Hospital, 52074 Aachen, Germany
| | - Yusuke Kubo
- Department of Anatomy and Cell Biology, RWTH Aachen University Hospital, 52074 Aachen, Germany
| | - Thomas Pufe
- Department of Anatomy and Cell Biology, RWTH Aachen University Hospital, 52074 Aachen, Germany
| | - Tim Ruhl
- Hand Surgery-Burn Center, Department of Plastic Surgery, RWTH Aachen University Hospital, 52074 Aachen, Germany
| | - Justus P Beier
- Hand Surgery-Burn Center, Department of Plastic Surgery, RWTH Aachen University Hospital, 52074 Aachen, Germany
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28
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Feng P, Luo Y, Ke C, Qiu H, Wang W, Zhu Y, Hou R, Xu L, Wu S. Chitosan-Based Functional Materials for Skin Wound Repair: Mechanisms and Applications. Front Bioeng Biotechnol 2021; 9:650598. [PMID: 33681176 PMCID: PMC7931995 DOI: 10.3389/fbioe.2021.650598] [Citation(s) in RCA: 227] [Impact Index Per Article: 56.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 02/01/2021] [Indexed: 02/06/2023] Open
Abstract
Skin wounds not only cause physical pain for patients but also are an economic burden for society. It is necessary to seek out an efficient approach to promote skin repair. Hydrogels are considered effective wound dressings. They possess many unique properties like biocompatibility, biodegradability, high water uptake and retention etc., so that they are promising candidate materials for wound healing. Chitosan is a polymeric biomaterial obtained by the deacetylation of chitin. With the properties of easy acquisition, antibacterial and hemostatic activity, and the ability to promote skin regeneration, hydrogel-like functional wound dressings (represented by chitosan and its derivatives) have received extensive attentions for their effectiveness and mechanisms in promoting skin wound repair. In this review, we extensively discussed the mechanisms with which chitosan-based functional materials promote hemostasis, anti-inflammation, proliferation of granulation in wound repair. We also provided the latest information about the applications of such materials in wound treatment. In addition, we summarized the methods to enhance the advantages and maintain the intrinsic nature of chitosan via incorporating other chemical components, active biomolecules and other substances into the hydrogels.
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Affiliation(s)
- Peipei Feng
- School of Medicine, Ningbo University, Ningbo, China
| | - Yang Luo
- School of Medicine, Ningbo University, Ningbo, China
| | - Chunhai Ke
- Lihuili Hospital, Affiliated Hospital of Ningbo University, Ningbo, China
| | - Haofeng Qiu
- School of Medicine, Ningbo University, Ningbo, China
| | - Wei Wang
- School of Medicine, Ningbo University, Ningbo, China
| | - Yabin Zhu
- School of Medicine, Ningbo University, Ningbo, China
| | - Ruixia Hou
- School of Medicine, Ningbo University, Ningbo, China
| | - Long Xu
- School of Materials Science and Chemical Engineering, Ningbo University, Ningbo, China
| | - Songze Wu
- Ningbo Baoting Biotechnology Co., Ltd., Ningbo, China
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29
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Water-transport and intracellular ice formation of human adipose-derived stem cells during freezing. J Therm Biol 2020; 93:102689. [PMID: 33077114 DOI: 10.1016/j.jtherbio.2020.102689] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Revised: 07/22/2020] [Accepted: 08/05/2020] [Indexed: 11/22/2022]
Abstract
The key to optimizing the cryopreservation strategy of human adipose-derived stem cells (hADSCs) is to identify the biophysical characteristics during freezing. Systematic freezing experiments were conducted under a cryo-microscope system to investigate the cryoinjury mechanism for hADSCs at different cooling rates. By simultaneously fitting morphological change data to the water-transport equation at 5, 10 and 20 °C/min, the plasma membrane hydraulic conductivity, Lpg, and activation energy, ELp, were determined. Moreover, the optimal cooling rate was also predicted by using mathematical model methods. Additionally, the surface-catalyzed nucleation (SCN) parameters were calculated by fitting in numerical models, Ω0SCN and k0SCN were determined at cooling rates of 30, 45 and 60 °C/min. These results may provide potential application value for cryopreservation of hADSCs.
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Takagi T, Kabata T, Hayashi K, Fang X, Kajino Y, Inoue D, Ohmori T, Ueno T, Yoshitani J, Ueoka K, Yamamuro Y, Tsuchiya H. Periodic injections of adipose-derived stem cell sheets attenuate osteoarthritis progression in an experimental rabbit model. BMC Musculoskelet Disord 2020; 21:691. [PMID: 33076883 PMCID: PMC7574575 DOI: 10.1186/s12891-020-03718-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Accepted: 10/13/2020] [Indexed: 12/05/2022] Open
Abstract
Background Subcutaneous adipose tissue represents an abundant source of multipotent adult stem cells named as Adipose-derived stem cells (ADSCs). With a cell sheet approach, ADSCs survive longer, and can be delivered in large quantities. We investigated whether intra-articular ADSC sheets attenuated osteoarthritis (OA) progression in a rabbit anterior cruciate ligament transection (ACLT) model. Methods Fabricating medium containing ascorbate-2-phosphate was used to enhance collagen protein secretion by the ADSCs to make ADSC sheets. At 4 weeks after ACLT, autologous ADSC sheets were injected intra-articularly into the right knee (ADSC sheets group), and autologous cell death sheets treated by liquid nitrogen were injected into the left knee (control group). Subsequent injections were administered once weekly. Femoral condyles were compared macroscopically and histologically. Results Macroscopically, OA progression was significantly milder in the ADSC sheets than in the control groups. Histologically, control knees showed obvious erosions in the medial and lateral condyles, while cartilage was retained predominantly in the ADSC sheets group. Immunohistochemically, MMP-1, MMP-13, ADAMTS-4 were less expressive in the ADSC sheets than in the control groups. Conclusions Periodic ADSC sheets injections inhibited articular cartilage degeneration without inducing any adverse effects. A large quantity of autologous ADSCs delivered by cell sheets homed to the synovium and protected chondrocytes.
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Affiliation(s)
- Tomoharu Takagi
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa university, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
| | - Tamon Kabata
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa university, 13-1 Takara-machi, Kanazawa, 920-8641, Japan.
| | - Katsuhiro Hayashi
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa university, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
| | - Xiang Fang
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa university, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
| | - Yoshitomo Kajino
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa university, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
| | - Daisuke Inoue
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa university, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
| | - Takaaki Ohmori
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa university, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
| | - Takuro Ueno
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa university, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
| | - Junya Yoshitani
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa university, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
| | - Ken Ueoka
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa university, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
| | - Yuki Yamamuro
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa university, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
| | - Hiroyuki Tsuchiya
- Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa university, 13-1 Takara-machi, Kanazawa, 920-8641, Japan
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31
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Chemically Defined, Clinical-Grade Cryopreservation of Human Adipose Stem Cells. Methods Mol Biol 2020. [PMID: 32797434 DOI: 10.1007/978-1-0716-0783-1_28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2023]
Abstract
Adipose-derived stem cells (ASCs) reside in the stromal compartment of adipose tissue and can be easily harvested in large quantities through a clinically safe liposuction procedure. ASCs do not induce immunogenic reactions and rather exert immunosuppressive effects. Therefore, they can be used for both autologous and allogeneic transplantations. They hold great promise for cell-based therapies and tissue engineering. A prerequisite to the realization of this promise is the development of successful cryopreservation methods for ASCs. In this chapter, we describe a xeno-free- and chemically defined cryopreservation protocol, which can be used for various clinical applications of ASCs.
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An immortalized human adipose-derived stem cell line with highly enhanced chondrogenic properties. Biochem Biophys Res Commun 2020; 530:252-258. [PMID: 32828295 DOI: 10.1016/j.bbrc.2020.07.016] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 07/04/2020] [Indexed: 12/28/2022]
Abstract
Human adipose-derived stem cells (ASCs) are a commonly used cell type for cartilage tissue engineering. However, donor-to-donor variability, cell heterogeneity, inconsistent chondrogenic potential, and limited expansion potential can hinder the use of these cells for modeling chondrogenesis, in vitro screening of drugs and treatments for joint diseases, or translational applications for tissue engineered cartilage repair. The goal of this study was to create an immortalized ASC line that showed enhanced and consistent chondrogenic potential for applications in cartilage tissue engineering as well as to provide a platform for investigation of biological and mechanobiological pathways involved in cartilage homeostasis and disease. Starting with the ASC52telo cell line, a hTERT-immortalized ASC line, we used lentivirus to overexpress SOX9, a master regulator of chondrogenesis, and screened several clonal populations of SOX9 overexpressing cells to form a new stable cell line with high chondrogenic potential. One clonal line, named ASC52telo-SOX9, displayed increased GAG and type II collagen synthesis and was found to be responsive to both mechanical and inflammatory stimuli in a manner similar to native chondrocytes. The development of a clonal line such as ASC52telo-SOX9 has the potential to be a powerful tool for studying cartilage homeostasis and disease mechanisms in vitro, and potentially as a platform for in vitro drug screening for diseases that affect articular cartilage. Our findings provide an approach for the development of other immortalized cell lines with improved chondrogenic capabilities in ASCs or other adult stem cells.
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Tsai CC, Kuo SH, Lu TY, Cheng NC, Shie MY, Yu J. Enzyme-Cross-linked Gelatin Hydrogel Enriched with an Articular Cartilage Extracellular Matrix and Human Adipose-Derived Stem Cells for Hyaline Cartilage Regeneration of Rabbits. ACS Biomater Sci Eng 2020; 6:5110-5119. [PMID: 33455262 DOI: 10.1021/acsbiomaterials.9b01756] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Hyaline cartilage regeneration remains clinically challenging. In this study, microbial transglutaminase was used to cross-link gelatin. The articular cartilage extracellular matrix (cECM), mainly comprising collagen type II and glycosaminoglycans (GAGs), which can support chondrogenesis, was enclosed in this enzyme-catalyzed hydrogel. After human adipose-derived stem cells (hASCs) were encapsulated in the hydrogel enriched with the cECM, the results demonstrated that the enzymatic cross-linking reaction is of low cytotoxicity. Moreover, the stem cells showed great proliferation and chondrogenic differentiation potential in the hydrogel. Most importantly, we assessed the therapeutic effects of applying a hydrogel enriched with the cECM and hASCs to repair a full-thickness osteochondral defect. At 8 weeks after surgery, the GCC group (hydrogel encapsulating cells and the cECM) exhibited a smooth articular surface with transparent new hyaline-like tissue macroscopically. According to histological analysis, inflammatory responses were hardly observed, and sound chondrocytes were aligned in the newly formed chondral layer. In addition, the GCC group exhibited significant improvement in the GAG content between weeks 4 and 8. In summary, the implantation of a gelatin hydrogel enriched with the cECM and hASCs could facilitate the hyaline cartilage regeneration significantly in rabbit knee joint models.
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Affiliation(s)
- Ching-Cheng Tsai
- Department of Chemical Engineering, National Taiwan University, No.1, Sec. 4, Roosevelt Rd., Da'an Dist., Taipei City 10617, Taiwan
| | - Shuo-Hsiu Kuo
- Department of Chemical Engineering, National Taiwan University, No.1, Sec. 4, Roosevelt Rd., Da'an Dist., Taipei City 10617, Taiwan
| | - Ting-Yu Lu
- Department of Chemical Engineering, National Taiwan University, No.1, Sec. 4, Roosevelt Rd., Da'an Dist., Taipei City 10617, Taiwan
| | - Nai-Chen Cheng
- Department of Surgery, National Taiwan University Hospital, No.1, Changde St., Zhongzheng Dist., Taipei City 10048, Taiwan
| | - Ming-You Shie
- Department of Dentistry, China Medical University, No.91 Hsueh-Shih Rd., Taichung City 40402, Taiwan
| | - Jiashing Yu
- Department of Chemical Engineering, National Taiwan University, No.1, Sec. 4, Roosevelt Rd., Da'an Dist., Taipei City 10617, Taiwan
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Archacka K, Bem J, Brzoska E, Czerwinska AM, Grabowska I, Kasprzycka P, Hoinkis D, Siennicka K, Pojda Z, Bernas P, Binkowski R, Jastrzebska K, Kupiec A, Malesza M, Michalczewska E, Soszynska M, Ilach K, Streminska W, Ciemerych MA. Beneficial Effect of IL-4 and SDF-1 on Myogenic Potential of Mouse and Human Adipose Tissue-Derived Stromal Cells. Cells 2020; 9:cells9061479. [PMID: 32560483 PMCID: PMC7349575 DOI: 10.3390/cells9061479] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 06/09/2020] [Accepted: 06/10/2020] [Indexed: 12/11/2022] Open
Abstract
Under physiological conditions skeletal muscle regeneration depends on the satellite cells. After injury these cells become activated, proliferate, and differentiate into myofibers reconstructing damaged tissue. Under pathological conditions satellite cells are not sufficient to support regeneration. For this reason, other cells are sought to be used in cell therapies, and different factors are tested as a tool to improve the regenerative potential of such cells. Many studies are conducted using animal cells, omitting the necessity to learn about human cells and compare them to animal ones. Here, we analyze and compare the impact of IL-4 and SDF-1, factors chosen by us on the basis of their ability to support myogenic differentiation and cell migration, at mouse and human adipose tissue-derived stromal cells (ADSCs). Importantly, we documented that mouse and human ADSCs differ in certain reactions to IL-4 and SDF-1. In general, the selected factors impacted transcriptome of ADSCs and improved migration and fusion ability of cells in vitro. In vivo, after transplantation into injured muscles, mouse ADSCs more eagerly participated in new myofiber formation than the human ones. However, regardless of the origin, ADSCs alleviated immune response and supported muscle reconstruction, and cytokine treatment enhanced these effects. Thus, we documented that the presence of ADSCs improves skeletal muscle regeneration and this influence could be increased by cell pretreatment with IL-4 and SDF-1.
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Affiliation(s)
- Karolina Archacka
- Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (K.A.); (J.B.); (E.B.); (A.M.C.); (I.G.); (P.K.); (P.B.); (R.B.); (K.J.); (A.K.); (M.M.); (E.M.); (M.S.); (K.I.); (W.S.)
| | - Joanna Bem
- Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (K.A.); (J.B.); (E.B.); (A.M.C.); (I.G.); (P.K.); (P.B.); (R.B.); (K.J.); (A.K.); (M.M.); (E.M.); (M.S.); (K.I.); (W.S.)
| | - Edyta Brzoska
- Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (K.A.); (J.B.); (E.B.); (A.M.C.); (I.G.); (P.K.); (P.B.); (R.B.); (K.J.); (A.K.); (M.M.); (E.M.); (M.S.); (K.I.); (W.S.)
| | - Areta M. Czerwinska
- Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (K.A.); (J.B.); (E.B.); (A.M.C.); (I.G.); (P.K.); (P.B.); (R.B.); (K.J.); (A.K.); (M.M.); (E.M.); (M.S.); (K.I.); (W.S.)
| | - Iwona Grabowska
- Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (K.A.); (J.B.); (E.B.); (A.M.C.); (I.G.); (P.K.); (P.B.); (R.B.); (K.J.); (A.K.); (M.M.); (E.M.); (M.S.); (K.I.); (W.S.)
| | - Paulina Kasprzycka
- Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (K.A.); (J.B.); (E.B.); (A.M.C.); (I.G.); (P.K.); (P.B.); (R.B.); (K.J.); (A.K.); (M.M.); (E.M.); (M.S.); (K.I.); (W.S.)
| | - Dzesika Hoinkis
- Intelliseq Ltd., Stanisława Konarskiego 42/13, 30-046 Krakow, Poland;
| | - Katarzyna Siennicka
- Department of Regenerative Medicine, Maria Sklodowska-Curie National Research Institute of Oncology, W.K. Roentgena 5, 02-781 Warsaw, Poland; (K.S.); (Z.P.)
| | - Zygmunt Pojda
- Department of Regenerative Medicine, Maria Sklodowska-Curie National Research Institute of Oncology, W.K. Roentgena 5, 02-781 Warsaw, Poland; (K.S.); (Z.P.)
| | - Patrycja Bernas
- Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (K.A.); (J.B.); (E.B.); (A.M.C.); (I.G.); (P.K.); (P.B.); (R.B.); (K.J.); (A.K.); (M.M.); (E.M.); (M.S.); (K.I.); (W.S.)
| | - Robert Binkowski
- Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (K.A.); (J.B.); (E.B.); (A.M.C.); (I.G.); (P.K.); (P.B.); (R.B.); (K.J.); (A.K.); (M.M.); (E.M.); (M.S.); (K.I.); (W.S.)
| | - Kinga Jastrzebska
- Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (K.A.); (J.B.); (E.B.); (A.M.C.); (I.G.); (P.K.); (P.B.); (R.B.); (K.J.); (A.K.); (M.M.); (E.M.); (M.S.); (K.I.); (W.S.)
| | - Aleksandra Kupiec
- Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (K.A.); (J.B.); (E.B.); (A.M.C.); (I.G.); (P.K.); (P.B.); (R.B.); (K.J.); (A.K.); (M.M.); (E.M.); (M.S.); (K.I.); (W.S.)
| | - Malgorzata Malesza
- Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (K.A.); (J.B.); (E.B.); (A.M.C.); (I.G.); (P.K.); (P.B.); (R.B.); (K.J.); (A.K.); (M.M.); (E.M.); (M.S.); (K.I.); (W.S.)
| | - Emilia Michalczewska
- Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (K.A.); (J.B.); (E.B.); (A.M.C.); (I.G.); (P.K.); (P.B.); (R.B.); (K.J.); (A.K.); (M.M.); (E.M.); (M.S.); (K.I.); (W.S.)
| | - Marta Soszynska
- Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (K.A.); (J.B.); (E.B.); (A.M.C.); (I.G.); (P.K.); (P.B.); (R.B.); (K.J.); (A.K.); (M.M.); (E.M.); (M.S.); (K.I.); (W.S.)
| | - Katarzyna Ilach
- Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (K.A.); (J.B.); (E.B.); (A.M.C.); (I.G.); (P.K.); (P.B.); (R.B.); (K.J.); (A.K.); (M.M.); (E.M.); (M.S.); (K.I.); (W.S.)
| | - Wladyslawa Streminska
- Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (K.A.); (J.B.); (E.B.); (A.M.C.); (I.G.); (P.K.); (P.B.); (R.B.); (K.J.); (A.K.); (M.M.); (E.M.); (M.S.); (K.I.); (W.S.)
| | - Maria A. Ciemerych
- Department of Cytology, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Ilji Miecznikowa 1, 02-096 Warsaw, Poland; (K.A.); (J.B.); (E.B.); (A.M.C.); (I.G.); (P.K.); (P.B.); (R.B.); (K.J.); (A.K.); (M.M.); (E.M.); (M.S.); (K.I.); (W.S.)
- Correspondence: ; Tel.: +48-22-55-42-216
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Cui Q, Zhang D, Kong D, Tang J, Liao X, Yang Q, Ren J, Gong Y, Wu G. Co-transplantation with adipose-derived cells to improve parathyroid transplantation in a mice model. Stem Cell Res Ther 2020; 11:200. [PMID: 32456711 PMCID: PMC7249357 DOI: 10.1186/s13287-020-01733-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 04/29/2020] [Accepted: 05/15/2020] [Indexed: 12/15/2022] Open
Abstract
Background Accidentally removed parathyroid glands are still challenging in neck surgery, leading to hypoparathyroidism characterized with abnormally low levels of parathyroid hormone. Parathyroid auto-transplantation is usually applied in compensation. To improve the efficiency of parathyroid transplantation, we introduced a method by co-transplanting with adipose-derived cells, including stromal vascular fractions (SVFs) and adipose-derived stem cells (ADSCs), and investigated the underlying molecular mechanisms involved in parathyroid transplantation survival. Methods Rat and human parathyroid tissues were transplanted into nude mice as parathyroid transplantation model to examine the effects of SVFs and ADSCs on grafts angiogenesis and survival rates, including blood vessel assembly and parathyroid hormone levels. Several angiogenic factors, such as vascular endothelial growth factor (VEGF)-A and fibroblast growth factor (FGF) 2, were assessed in parathyroid grafts. The effects of hypoxia were investigated on ADSCs. The modulatory roles of the eyes absent homolog 1 (EYA1), which is vital in parathyroid development, was also investigated on angiogenic factor production and secretion by ADSCs. All experimental data were statistically processed. Student’s t test was used to assess significant differences between 2 groups. For multiple comparisons with additional interventions, two-way ANOVA followed by Tukey’s post hoc test was performed. P < 0.05 was considered as significant. Results SVFs improve rat parathyroid transplantation survival and blood vessel assembly, as well as FGF2 and VEGF-A expression levels in parathyroid transplantation mice. Functional human parathyroid grafts have higher microvessel density and increased VEGF-A expression. The supernatant of ADSCs induced tubule formation and migration of human endothelial cells in vitro. Hypoxia had no effect on proliferation and apoptosis of human ADSCs but induced higher angiogenic factor levels of VEGF-A and FGF2, modulated by EYA1, which was confirmed by parathyroid glands transplantation in mice. Conclusions Adipose-derived cells, including ADSCs and SVFs, improve parathyroid transplantation survival via promoting angiogenesis through EYA1-regulating angiogenetic factors in vitro and in vivo. Our studies proved an effective method to improve the parathyroid autotransplantation, which is promising for clinical patients with hypoparathyroidism when parathyroid glands were accidentally injured, removed, or devascularized.
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Affiliation(s)
- Qiuxia Cui
- Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, China
| | - Dan Zhang
- Department of Anesthesiology, Xiamen Branch, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Deguang Kong
- Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, China
| | - Jianing Tang
- Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, China
| | - Xing Liao
- Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, China
| | - Qian Yang
- Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, China
| | - Jiangbo Ren
- Department of Biological Repositories, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, China
| | - Yan Gong
- Department of Biological Repositories, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, China.
| | - Gaosong Wu
- Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, China.
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Lin IC, Wang TJ, Wu CL, Lu DH, Chen YR, Yang KC. Chitosan-cartilage extracellular matrix hybrid scaffold induces chondrogenic differentiation to adipose-derived stem cells. Regen Ther 2020; 14:238-244. [PMID: 32435677 PMCID: PMC7229425 DOI: 10.1016/j.reth.2020.03.014] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 03/19/2020] [Accepted: 03/25/2020] [Indexed: 12/12/2022] Open
Abstract
Introduction Adipose-derived stem cells (ASCs) are potential cell sources for cartilage tissue engineering. Chitosan has been shown to enhance the stemness and differentiation capability of ASCs, and the native extracellular matrix (ECM) derived from articular cartilage has been also reported to induce chondrogenic differentiation of ASCs. Here we tested the hypothesis that a porous three-dimensional (3D) hybrid scaffold composed of chitosan and cartilage ECM can provide a better environment to induce ASC chondrogenesis. Methods Mixed solution composed of chitosan and cartilage ECM was frozen and lyophilized to form a composite construct. The porous 3D scaffolds were further crosslinked by genipin and used for ASC culture. Results Cultivation of ASCs in the chitosan/cartilage ECM composite 3D scaffolds induced the formation of cell spheroids with profound glycosaminoglycan production after 14 and 28 days culture. Chondrogenesis of ASCs seeded in the 3D scaffolds was also evident by mRNA expressions of cartilage-specific gene COL2A1 and ACAN on day 14. Histology and immunohistochemistry on day 28 also showed abundant cartilage-specific macromolecules, namely collagen type II and proteoglycan, deposited in a surface layer of the composite scaffold with tangential layer, transitional layer, and lacunae-like structures. Otherwise, hypertrophic markers collagen type I and X were concentrated in the area beneath the surface. Conclusion Our findings demonstrated spatial chondrogenic differentiation of ASCs in the chitosan-cartilage ECM composite scaffolds. This 3D hybrid scaffold exhibits great potentials for ASC-based cartilage tissue engineering.
Cultivation of ASCs in the chitosan and cartilage ECM hybrid scaffold induced chondrogenesis. ASCs in composite scaffold expressed cartilage-specific genes COL2A1 and ACAN. Histologic inspections showed abundant cartilage-specific collagen type II and proteoglycan productions. Chitosan-cartilage ECM hybrid scaffold exhibits great potentials for ASC-based cartilage tissue engineering.
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Affiliation(s)
- I-Chan Lin
- Department of Ophthalmology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan.,Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Tsung-Jen Wang
- Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.,Department of Ophthalmology, Taipei Medical University Hospital, Taipei 11031, Taiwan
| | - Chien-Liang Wu
- Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.,Department of Ophthalmology, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan
| | - Dai-Hua Lu
- School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Yi-Ru Chen
- School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Kai-Chiang Yang
- School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei 11031, Taiwan
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IL-4 and SDF-1 Increase Adipose Tissue-Derived Stromal Cell Ability to Improve Rat Skeletal Muscle Regeneration. Int J Mol Sci 2020; 21:ijms21093302. [PMID: 32392778 PMCID: PMC7246596 DOI: 10.3390/ijms21093302] [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: 03/13/2020] [Revised: 05/01/2020] [Accepted: 05/04/2020] [Indexed: 12/18/2022] Open
Abstract
Skeletal muscle regeneration depends on the satellite cells, which, in response to injury, activate, proliferate, and reconstruct damaged tissue. However, under certain conditions, such as large injuries or myopathies, these cells might not sufficiently support repair. Thus, other cell populations, among them adipose tissue-derived stromal cells (ADSCs), are tested as a tool to improve regeneration. Importantly, the pro-regenerative action of such cells could be improved by various factors. In the current study, we tested whether IL-4 and SDF-1 could improve the ability of ADSCs to support the regeneration of rat skeletal muscles. We compared their effect at properly regenerating fast-twitch EDL and poorly regenerating slow-twitch soleus. To this end, ADSCs subjected to IL-4 and SDF-1 were analyzed in vitro and also in vivo after their transplantation into injured muscles. We tested their proliferation rate, migration, expression of stem cell markers and myogenic factors, their ability to fuse with myoblasts, as well as their impact on the mass, structure and function of regenerating muscles. As a result, we showed that cytokine-pretreated ADSCs had a beneficial effect in the regeneration process. Their presence resulted in improved muscle structure and function, as well as decreased fibrosis development and a modulated immune response.
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Cheng J, Zhao ZW, Wen JR, Wang L, Huang LW, Yang YL, Zhao FN, Xiao JY, Fang F, Wu J, Miao YL. Status, challenges, and future prospects of stem cell therapy in pelvic floor disorders. World J Clin Cases 2020; 8:1400-1413. [PMID: 32368533 PMCID: PMC7190946 DOI: 10.12998/wjcc.v8.i8.1400] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 03/30/2020] [Accepted: 04/08/2020] [Indexed: 02/05/2023] Open
Abstract
Pelvic floor disorders (PFDs) represent a group of common and frequently-occurring diseases that seriously affect the life quality of women, generally including stress urinary incontinence and pelvic organ prolapse. Surgery has been used as a treatment for PFD, but almost 30% of patients require subsequent surgery due to a high incidence of postoperative complications and high recurrence rates. Therefore, investigations of new therapeutic strategies are urgently needed. Stem cells possess strong multi-differentiation, self-renewal, immunomodulation, and angiogenesis abilities and they are able to differentiate into various cell types of pelvic floor tissues and thus provide a potential therapeutic approach for PFD. Recently, various studies using different autologous stem cells have achieved promising results by improving the pelvic ligament and muscle regeneration and conferring the tissue elasticity and strength to the damaged tissue in PFD, as well as reduced inflammatory reactions, collagen deposition, and foreign body reaction. However, with relatively high rates of complications such as bladder stone formation and wound infections, further studies are necessary to investigate the role of stem cells as maintainers of tissue homeostasis and modulators in early interventions including therapies using new stem cell sources, exosomes, and tissue-engineering combined with stem cell-based implants, among others. This review describes the types of stem cells and the possible interaction mechanisms in PFD treatment, with the hope of providing more promising stem cell treatment strategies for PFD in the future.
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Affiliation(s)
- Juan Cheng
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, West China Campus, Sichuan University, Chengdu 610041, Sichuan Province, China
- Deep Underground Space Medical Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Zhi-Wei Zhao
- West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ji-Rui Wen
- West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ling Wang
- Deep Underground Space Medical Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Li-Wei Huang
- West China School of Stomatology Medicine, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yan-Lin Yang
- West China School of Medicine/West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Feng-Nian Zhao
- West China School of Medicine/West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jing-Yue Xiao
- West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Fei Fang
- West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jiang Wu
- Deep Underground Space Medical Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ya-Li Miao
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, West China Campus, Sichuan University, Chengdu 610041, Sichuan Province, China
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Yilmaz AB, Tapsin S, Elbasan EB, Kayhan HD, Sahin F, Turkel N. Suppressor Effects of Sodium Pentaborate Pentahydrate and Pluronic F68 on Adipogenic Differentiation and Fat Accumulation. Biol Trace Elem Res 2020; 193:390-399. [PMID: 31119640 DOI: 10.1007/s12011-019-01738-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 04/17/2019] [Indexed: 10/26/2022]
Abstract
Obesity is a major public health problem worldwide and a risk factor for certain diseases, including cardiovascular disease, diabetes, cancer, and depression. Unfortunately, currently available anti-obesity drugs have failed in the long-term maintenance of weight control. It has been a challenge to design novel drugs that could potentially treat obesity or prevent uncontrolled weight-gain which lies underneath the pathology of obesity. Since obesity in a way is a consequence of the accumulating new mature adipocytes from undifferentiated precursors which is a process also termed as adipogenesis, drugs that might control adipogenesis could be beneficial for the treatment of obesity. In the current study, combined effect of sodium pentaborate pentahydrate (NaB) and pluronic F68 on adipogenic differentiation was examined by administering various combinations of the two agents to human adipose-derived stem cells (hADSCs) in in vitro. Immunocytochemistry and quantitative RT-PCR were performed to evaluate the levels of adipogenesis-promoting genes such as peroxisome proliferator-activated receptor-γ (PPARγ), fatty acid binding protein (FABP4), and adiponectin. Results indicated that expressions of all these three genes were restrained. Furthermore, Oil Red O staining revealed that lipid vesicle formation was reduced in hADSCs treated with differentiation medium containing NaB/F68 combination. Finally, expression levels of Hippo pathway kinases Lats2, MST1, and scaffold protein Sav1 were reduced in these cells, suggesting a possible link between Hippo pathway-dependent downregulation of PPARγ and the NaB/F68 treatment. Herein, we showed that combination of NaB and F68 curtails adipocyte differentiation by inhibiting the adipogenic transcriptional program leading to a decrease in lipid accumulation in adipocytes even at very low doses, thereby uncovered a striking opportunity to use this combination in obesity treatment.
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Affiliation(s)
- Aysu Bilge Yilmaz
- Faculty of Engineering, Department of Genetics and Bioengineering, Yeditepe University, Kayışdağı, 34755, Istanbul, Turkey
- Koc Universitesi Hastanesi, Davutpasa Cd No:4, Topkapi Zeytinburnu, 34090, Istanbul, Turkey
| | - Sidika Tapsin
- Faculty of Engineering, Department of Genetics and Bioengineering, Yeditepe University, Kayışdağı, 34755, Istanbul, Turkey
- Stem Cell and Development Biology, Genome Institute of Singapore, Singapore, 138672, Singapore
| | - Elif Burce Elbasan
- Faculty of Engineering, Department of Genetics and Bioengineering, Yeditepe University, Kayışdağı, 34755, Istanbul, Turkey
| | - Hatice Damla Kayhan
- Faculty of Engineering, Department of Genetics and Bioengineering, Yeditepe University, Kayışdağı, 34755, Istanbul, Turkey
- Yaşam Bilimleri ve Teknolojileri Uygulama ve Araştırma Merkezi, Boğaziçi Üniversitesi, Kuzey Kampüs ETA-B Blok. 4.Kat, 34342, Bebek/Istanbul, Turkey
| | - Fikrettin Sahin
- Faculty of Engineering, Department of Genetics and Bioengineering, Yeditepe University, Kayışdağı, 34755, Istanbul, Turkey
| | - Nezaket Turkel
- Faculty of Engineering, Department of Genetics and Bioengineering, Yeditepe University, Kayışdağı, 34755, Istanbul, Turkey.
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Uchimura R, Ueda T, Fukazawa R, Hayakawa J, Ohashi R, Nagi-Miura N, Ohno N, Migita M, Itoh Y. Adipose tissue-derived stem cells suppress coronary arteritis of Kawasaki disease in vivo. Pediatr Int 2020; 62:14-21. [PMID: 31758839 DOI: 10.1111/ped.14062] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 08/06/2019] [Accepted: 09/30/2019] [Indexed: 01/08/2023]
Abstract
BACKGROUND Kawasaki disease (KD) is a systemic inflammatory disease resulting in an acute febrile syndrome commonly affecting children younger than 5 years. Coronary arteritis in KD is occasionally non-responsive to several treatments. Recently, adipose tissue-derived stem cells (ADSCs) have been shown to have anti-inflammatory, immunosuppressive, and tissue-repair characteristics and are considered a useful treatment for inflammatory disease. The present study aimed to elucidate whether the administration of ADSCs can suppress KD-associated vasculitis in vivo. METHODS Candida albicans water-soluble fraction is often used to model KD via the induction of severe coronary arteritis. Kawasaki disease model mice were intravenously administered ADSCs and phosphate-buffered saline (PBS). On day 29, the mice were sacrificed and hearts from mice in each group were dissected. This was followed by serum collection. Cardiac tissue sections were subjected to histopathological examination to evaluate the inflammatory area. The levels of pro-inflammatory cytokines in the serum were analyzed at days 15 and 29. The survival rates of both groups were compared. RESULTS The mean inflammatory area in coronary arteritis was significantly lower in the ADSC group compared to the PBS group (P < 0.01). Furthermore, the levels of pro-inflammatory cytokines, such as IL-1β, IL-12, IL-17, RANTES, INF-γ, and TNF-α, in the ADSC group were significantly lower than those in the PBS group. Moreover, the ADSC group had a significantly higher survival rate than the PBS group. CONCLUSIONS These findings highlight that ADSCs have anti-inflammatory and immune regulatory functions that could provide novel cell-based therapeutic strategies for severe KD.
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Affiliation(s)
- Ryoichi Uchimura
- Department of Pediatrics, Nippon Medical School, Sendagi, Tokyo, Japan
| | - Takahiro Ueda
- Department of Pediatrics, Nippon Medical School, Sendagi, Tokyo, Japan
| | - Ryuji Fukazawa
- Department of Pediatrics, Nippon Medical School, Sendagi, Tokyo, Japan
| | - Jun Hayakawa
- Department of Pediatrics, Nippon Medical School, Sendagi, Tokyo, Japan
| | - Ryuji Ohashi
- Department of Pathology, Nippon Medical School, Sendagi, Tokyo, Japan
| | - Noriko Nagi-Miura
- Laboratory for Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan
| | - Naohito Ohno
- Laboratory for Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan
| | - Makoto Migita
- Department of Pediatrics, Nippon Medical School, Sendagi, Tokyo, Japan
| | - Yasuhiko Itoh
- Department of Pediatrics, Nippon Medical School, Sendagi, Tokyo, Japan
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Lee GW, Mun JU, Ahn MW. The impact of posterior epidural adipose tissue on postoperative outcomes after posterior decompression surgery for lumbar spinal stenosis: A prospectively randomized non-inferiority trial. J Orthop Surg (Hong Kong) 2020; 28:2309499019896871. [PMID: 31908178 DOI: 10.1177/2309499019896871] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
STUDY DESIGN The present study is a prospectively randomized study. OBJECTIVE The objective of the study was to evaluate the impact of posterior epidural adipose tissue (PAT) on postoperative outcome following lumbar decompression surgery for lumbar spinal stenosis (LSS) by whether PAT was removed or preserved during the surgical procedure. SUMMARY OF BACKGROUND DATA In posterior decompression surgery for LSS, PAT is routinely removed without knowledge of its role and significance. However, considering adipose tissue has regenerative properties of damaged neighboring tissues or itself, PAT, which is adipose tissue located at peridural space, might also have a potential to regenerate the neighboring damaged tissue, including dura and nerve root in the lumbar spine, but this has not been thoroughly studied. METHODS Of the 185 eligible patients screened for the current study, 181 patients were enrolled and randomly allocated into either group A (PAT removal, n = 90) or group B (PAT retention, n = 91). The primary outcome measure was pain intensity on the lower back and lower extremity. The secondary outcome measures were functional outcome based on the Oswestry disability index (ODI) and walking distance, complications during the surgical procedure, and surgical outcomes. RESULTS Postoperative pain intensity on the lower back and lower extremity was greater in group A than in group B. Functional status on ODI and walking distance was also worse in group B than in group A (64.9% in group A and 66.2% in group B). The number of patients with aggravated pain intensity and deteriorated functional status in postoperative follow-up times was significantly greater in group A than in group B. There were no significant differences in surgical outcome and complications between the groups. CONCLUSION Preserving epidural fat may be favorable in postoperative outcomes of posterior decompression surgery for LSS compared to removing epidural fat.
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Affiliation(s)
- Gun Woo Lee
- Department of Orthopaedic Surgery, Spine Center, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Republic of Korea
| | - Jong-Uk Mun
- Department of Orthopaedic Surgery, Spine Center, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Republic of Korea
| | - Myun-Whan Ahn
- Department of Orthopaedic Surgery, Spine Center, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Republic of Korea
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Ma M, Wang C, Ao Y, He N, Hao F, Liang H, Liu D. HOXC10 promotes proliferation and attenuates lipid accumulation of sheep bone marrow mesenchymal stem cells. Mol Cell Probes 2019; 49:101491. [PMID: 31812713 DOI: 10.1016/j.mcp.2019.101491] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 12/03/2019] [Accepted: 12/04/2019] [Indexed: 01/19/2023]
Abstract
Homeodomain-containing gene C10 (HOXC10), known to regulate cell differentiation and proliferation, is a key negative regulator in the browning of white adipose tissue in mice. Sheep is an important farm animal that provides meat for human consumption, with fat content being an important meat quality determinant; however, there is no report about the role of HOXC10 in sheep adipocytes or adipogenesis. In this study, we investigated the effect of HOXC10 on proliferation and adipogenic differentiation in sheep bone marrow mesenchymal stem cells (sBMSCs). In sBMSCs, HOXC10 overexpression promoted cell proliferation and upregulated the expression of p-PI3K, p-AKT, p-p70S6K, p-MEK, and p-ERK, whereas HOXC10 knockdown was associated with the opposite effects. These results suggested that HOXC10 may promote cell proliferation by activating the MEK/ERK and PI3K/AKT/mTOR/p70S6K signaling pathways. In addition, we found that HOXC10 expression was negatively associated with lipid accumulation in adipogenic-differentiated sBMSCs. HOXC10 overexpression in sBMSCs significantly decreased lipid droplet accumulation and suppressed the expression of adipogenic-specific genes, including ACC, LPL, PPARG, and FABP4, while HOXC10 knockdown was associated with the opposite effects. Furthermore, our study suggested a new regulatory mechanism of the effect of HOXC10 on lipid accumulation and metabolism; HOXC10 may negatively regulate lipid accumulation in adipogenic-differentiated sBMSCs, at least in part, by suppressing LPL expression. Overall, our research not only contributes to a better understanding of the mechanism of lipid accumulation and metabolism in sheep, but also shed light on meat quality control in the future.
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Affiliation(s)
- Min Ma
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, Inner Mongolia, China
| | - Cuiru Wang
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, Inner Mongolia, China
| | - Yue Ao
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, Inner Mongolia, China
| | - Nimantana He
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, Inner Mongolia, China
| | - Fei Hao
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, Inner Mongolia, China
| | - Hao Liang
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, Inner Mongolia, China
| | - Dongjun Liu
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, Inner Mongolia University, Hohhot, Inner Mongolia, China.
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Ejaz A, Greenberger JS, Rubin PJ. Understanding the mechanism of radiation induced fibrosis and therapy options. Pharmacol Ther 2019; 204:107399. [DOI: 10.1016/j.pharmthera.2019.107399] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Accepted: 08/07/2019] [Indexed: 02/06/2023]
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Comparison of Properties of Stem Cells Isolated from Adipose Tissue and Lipomas in Dogs. Stem Cells Int 2019; 2019:1609876. [PMID: 31827523 PMCID: PMC6886319 DOI: 10.1155/2019/1609876] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 09/26/2019] [Accepted: 11/01/2019] [Indexed: 12/12/2022] Open
Abstract
Adipose-derived mesenchymal stem cells (ADSCs) have been suggested their benefits in regenerative medicine for various diseases. Lipomas, benign neoplasms in adipose tissue, have been reported as a potential source of stem cells. These lipoma-derived mesenchymal stem cells (LDSCs) may be useful for regenerative medicine. However, the detailed characteristics of LDSCs have not been fully elucidated. This study investigated the cellular proteomics and secretomes of canine LDSCs in addition to morphology and proliferation and differentiation capacities. Some LDSCs isolated from canine subcutaneous lipomas were morphologically different from ADSCs and showed a rounded shape instead of fibroblast-like morphology. The phenotype of cell surface markers in LDSCs was similar to those in ADSCs, but CD29 and CD90 stem cell markers were more highly expressed compared with those of ADSCs. LDSCs had noticeably high proliferation ability, but no significant differences were observed compared with ADSCs. In regard to differentiation capacity compared to ADSCs, LDSCs showed higher adipogenesis, but no differences were observed with osteogenesis. Cellular proteomic analysis using two-dimensional gel electrophoresis revealed that over 95% of protein spots showed similar expression levels between LDSCs and ADSCs. Secretome analysis was performed using iTRAQ and quantitative cytokine arrays. Over 1900 proteins were detected in conditioned medium (CM) of LDSCs and ADSCs, and 94.0% of detected proteins showed similar expression levels between CM of both cell types. Results from cytokine arrays including 20 cytokines showed no significant differences between CM of LDSCs and that of ADSCs. Our results indicate that canine LDSCs had variability in characteristics among individuals in contrast with those of ADSCs. Cellular proteomics and secretomes were similar in both LDSCs and ADSCs. These findings suggest that LDSCs may be suitable for application in regenerative medicine.
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Gonçalves AI, Berdecka D, Rodrigues MT, Eren AD, de Boer J, Reis RL, Gomes ME. Evaluation of tenogenic differentiation potential of selected subpopulations of human adipose-derived stem cells. J Tissue Eng Regen Med 2019; 13:2204-2217. [PMID: 31606945 DOI: 10.1002/term.2967] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 09/11/2019] [Accepted: 09/25/2019] [Indexed: 12/24/2022]
Abstract
Identification of a suitable cell source and bioactive agents guiding cell differentiation towards tenogenic phenotype represents a prerequisite for advancement of cell-based therapies for tendon repair. Human adipose-derived stem cells (hASCs) are a promising, yet intrinsically heterogenous population with diversified differentiation capacities. In this work, we investigated antigenically-defined subsets of hASCs expressing markers related to tendon phenotype or associated with pluripotency that might be more prone to tenogenic differentiation, when compared to unsorted hASCs. Subpopulations positive for tenomodulin (TNMD+ hASCs) and stage specific early antigen 4 (SSEA-4+ hASCs), as well as unsorted ASCs were cultured up to 21 days in basic medium or media supplemented with TGF-β3 (10 ng/ml), or GDF-5 (50 ng/ml). Cell response was evaluated by analysis of expression of tendon-related markers at gene level and protein level by real time RT-PCR, western blot, and immunocytochemistry. A significant upregulation of scleraxis was observed for both subpopulations and unsorted hASCs in the presence of TGF-β3. More prominent alterations in gene expression profile in response to TGF-β3 were observed for TNMD+ hASCs. Subpopulations evidenced an increased collagen III and TNC deposition in basal medium conditions in comparison with unsorted hASCs. In the particular case of TNMD+ hASCs, GDF-5 seems to influence more the deposition of TNC. Within hASCs populations, discrete subsets could be distinguished offering varied sensitivity to specific biochemical stimulation leading to differential expression of tenogenic components suggesting that cell subsets may have distinctive roles in the complex biological responses leading to tenogenic commitment to be further explored in cell based strategies for tendon tissues.
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Affiliation(s)
- Ana I Gonçalves
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal.,ICVS/3B's-PT Government Associate Laboratory, Braga, Portugal
| | - Dominika Berdecka
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal.,ICVS/3B's-PT Government Associate Laboratory, Braga, Portugal
| | - Márcia T Rodrigues
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal.,ICVS/3B's-PT Government Associate Laboratory, Braga, Portugal.,The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal
| | - Aysegul Dede Eren
- MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Cell Biology-Inspired Tissue Engineering, Maastricht, The Netherlands
| | - Jan de Boer
- MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Cell Biology-Inspired Tissue Engineering, Maastricht, The Netherlands
| | - Rui L Reis
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal.,ICVS/3B's-PT Government Associate Laboratory, Braga, Portugal.,The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal
| | - Manuela E Gomes
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal.,ICVS/3B's-PT Government Associate Laboratory, Braga, Portugal.,The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Guimarães, Portugal
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Zhang Y, Li D, Fang S, Li X, Zhang H, Dai H, Fan H, Li Y, Shen D, Tang W, Yang C, Xing X. Stimulatory effect of engineered three-layer adipose tissue-derived stem cells sheet in atelocollagen matrix on wound healing in a mouse model of radiation-induced skin injury. J Biomater Appl 2019; 34:498-508. [PMID: 31311392 DOI: 10.1177/0885328219862123] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Affiliation(s)
- Yuanzheng Zhang
- Shanghai Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Dan Li
- Shanghai Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Shuo Fang
- Shanghai Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Xueyang Li
- Shanghai Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Huojun Zhang
- Shanghai Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Haiying Dai
- Shanghai Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Hao Fan
- Shanghai Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Yingli Li
- Shanghai Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Di Shen
- Shanghai Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Weiya Tang
- Shanghai Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Chao Yang
- Shanghai Changhai Hospital, The Second Military Medical University, Shanghai, China
| | - Xin Xing
- Shanghai Changhai Hospital, The Second Military Medical University, Shanghai, China
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Viswanathan S, Shi Y, Galipeau J, Krampera M, Leblanc K, Martin I, Nolta J, Phinney DG, Sensebe L. Mesenchymal stem versus stromal cells: International Society for Cell & Gene Therapy (ISCT®) Mesenchymal Stromal Cell committee position statement on nomenclature. Cytotherapy 2019; 21:1019-1024. [PMID: 31526643 DOI: 10.1016/j.jcyt.2019.08.002] [Citation(s) in RCA: 514] [Impact Index Per Article: 85.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Accepted: 08/19/2019] [Indexed: 02/06/2023]
Abstract
The International Society for Cell & Gene Therapy (ISCT®) Mesenchymal Stromal Cell (ISCT MSC) committee offers a position statement to clarify the nomenclature of mesenchymal stromal cells (MSCs). The ISCT MSC committee continues to support the use of the acronym "MSCs" but recommends this be (i) supplemented by tissue-source origin of the cells, which would highlight tissue-specific properties; (ii) intended as MSCs unless rigorous evidence for stemness exists that can be supported by both in vitro and in vivo data; and (iii) associated with robust matrix of functional assays to demonstrate MSC properties, which are not generically defined but informed by the intended therapeutic mode of actions.
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Affiliation(s)
- S Viswanathan
- Arthritis Program, University Health Network, Krembil Research Institute, University Health Network, Cell Therapy Program, University Health Network, Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada.
| | - Y Shi
- The First Affiliated Hospital, Soochow University Institutes for Translational Medicine, Suzhou, China; Institute of Health Sciences, Chinese Academy of Sciences, Shanghai, China.
| | - J Galipeau
- Department of Medicine, University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, USA
| | - M Krampera
- Section of Hematology, Department of Medicine, University of Verona, Verona, Italy
| | - K Leblanc
- Division of Clinical Immunology and Transfusion Medicine, Karolinska Institutet, Stockholm, Sweden
| | - I Martin
- Department of Biomedicine, University Hospital Basel, Basel, Switzerland
| | - J Nolta
- Department of Internal Medicine, Stem Cell Program and Institute for Regenerative Cures, University of California Davis, Sacramento, California, USA
| | - D G Phinney
- Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, Florida, USA
| | - L Sensebe
- UMR5273 STROMALab CNRS/EFS/UPS-INSERM U1031, Toulouse, France
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Lee GW, Seo MS, Kang KK, Oh SK. Epidural Fat-Derived Mesenchymal Stem Cell: First Report of Epidural Fat-Derived Mesenchymal Stem Cell. Asian Spine J 2019; 13:361-367. [PMID: 30669827 PMCID: PMC6547395 DOI: 10.31616/asj.2018.0215] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Revised: 10/04/2018] [Accepted: 11/03/2018] [Indexed: 12/18/2022] Open
Abstract
STUDY DESIGN Experimental study. PURPOSE To determine whether epidural fat (EF) tissue contains mesenchymal stem cells (MSC). OVERVIEW OF LITERATURE Spine surgeons are unaware of the contents of EF tissue and the reason for its presence between the ligamentum flavum and the dura mater; therefore, EF tissues are routinely eliminated during surgical procedures. However, EF removal causes certain postoperative problems, such as post-laminectomy syndrome. We hypothesized that the EF tissue may play a significant supportive role for the neural structures and other nearby conditions. METHODS EF tissues were obtained from consenting patients (n=3) during posterior decompression surgery of the lumbar spine. The primary cells were isolated and cultured as per previously described methods with some modifications, and the cell morphology and cumulation were examined. Thereafter, reverse transcription-polymerase chain reaction (RT-PCR), a fluorescence-activated cell sorting (FACS) analysis, and differentiation potency for differentiation into osteoblasts, chondroblasts, and adipocytes were investigated to identify whether the cells derived from EF are MSC. RESULTS The cells from the EF tissue had a fibroblast or neuron-like morphology that persisted until the senescence at p18. MSCspecific genes, such as OCT4, SOX2, KLF4, MYC, and GAPDH were expressed in the RT-PCR study, while MSC-specific surface markers such as CD105, CD90, and CD73 were exhibited in the FACS analysis. The differentiation properties of EF-MSC for differentiation into the three types of cells (osteoblast, chondroblast, and adipocyte) were also confirmed. CONCLUSIONS Based on the cell culture, FACS analysis, RT-PCR analysis, and differentiation potent outcomes, all the features of the cells corresponded to MSC. This is the first study to identify EF-MSC derived from the EF tissue.
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Affiliation(s)
- Gun Woo Lee
- Department of Orthopaedic Surgery, Spine Center, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, Korea
| | - Min-Soo Seo
- Labaratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Korea
| | - Kyung-Ku Kang
- Labaratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Korea
| | - Se-Kyung Oh
- Labaratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Korea
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Thomson AL, Berent AC, Weisse C, Langston CE. Intra-arterial renal infusion of autologous mesenchymal stem cells for treatment of chronic kidney disease in cats: Phase I clinical trial. J Vet Intern Med 2019; 33:1353-1361. [PMID: 30924554 PMCID: PMC6524114 DOI: 10.1111/jvim.15486] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Accepted: 03/12/2019] [Indexed: 12/21/2022] Open
Abstract
Background There are no known treatments that halt or reverse chronic kidney disease (CKD) in cats. In rodent models, stem cell treatment has been associated with improvement in renal function parameters, especially when stem cells were delivered intra‐arterially to the kidney. To date, only IV and intrarenal stem cell infusions have been studied in cats with CKD with no clinically relevant improvement noted. Objective To assess the safety and feasibility of intra‐arterial delivery of autologous mesenchymal stem cells (MSC) in stromal vascular fraction (SVF) to the kidney in cats with CKD. Animals Five client‐owned domestic cats with International Renal Interest Society stage III CKD. Methods Prospective cohort study (phase I clinical trial). Adipose tissue was harvested from study animals on day 0. On days 2 and 14, an infusion of MSC in SVF was administered into the renal artery via the femoral or carotid artery using fluoroscopic guidance. Serum creatinine and blood urea nitrogen concentration, plasma iohexol clearance, and quality of life assessments were monitored between days 0 and 90. Results The procedure was performed successfully in all cats. No severe adverse events were observed in any cat during the study period. Conclusions and Clinical Importance Intra‐arterial infusion of MSC into the renal artery in CKD cats was feasible and safe within a 3‐month postoperative period. Efficacy and long‐term safety have yet to be established. This procedure requires careful technique and training.
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Affiliation(s)
- Abigail L Thomson
- The Animal Medical Center, Interventional Radiology and Endoscopy, New York, NY
| | - Allyson C Berent
- The Animal Medical Center, Interventional Radiology and Endoscopy, New York, NY
| | - Chick Weisse
- The Animal Medical Center, Interventional Radiology and Endoscopy, New York, NY
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Rivera-Izquierdo M, Cabeza L, Láinez-Ramos-Bossini A, Quesada R, Perazzoli G, Alvarez P, Prados J, Melguizo C. An updated review of adipose derived-mesenchymal stem cells and their applications in musculoskeletal disorders. Expert Opin Biol Ther 2019; 19:233-248. [PMID: 30653367 DOI: 10.1080/14712598.2019.1563069] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2018] [Accepted: 12/20/2018] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Adipose-derived mesenchymal stem cells (ASCs) represent a new therapeutic strategy in biomedicine with many potential applications, especially in musculoskeletal disorders. Preclinical and clinical studies based on the administration of ASCs support their efficacy in bone regeneration, joint repair, tendon injury and skeletal muscle alterations. Many of these novel treatments may improve patients' quality of life and prognosis. However, several concerns about the use of stem cells remain unsolved, particularly regarding their safety and side effects. The present work aims to review the nature, clinical trials and patents involving the use of ASCs in musculoskeletal disorders. AREAS COVERED In this article, we describe ASCs' isolation, culture and differentiation in vivo and in vitro, advances on ASCs' applications in bone, cartilage, muscle and tendon repair, and patents involving the use of ASCs. EXPERT OPINION The use of ASCs in musculoskeletal disorders presents significant therapeutic advantages, including limited autoimmune response, potential cell expansion ex vivo, high plasticity to differentiate into several mesodermal cell lineages, and additional effects of therapeutic interest such as secretion of neurotrophic factors and anti-inflammatory properties. For these reasons, ASCs are promising therapeutic agents for clinical applications in musculoskeletal disorders.
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Affiliation(s)
- Mario Rivera-Izquierdo
- a Department of Anatomy and Embryology, Faculty of Medicine , University of Granada , Granada , Spain
| | - Laura Cabeza
- a Department of Anatomy and Embryology, Faculty of Medicine , University of Granada , Granada , Spain
- b Institute of Biopathology and Regenerative Medicine (IBIMER), Biomedical Research Center (CIBM) , University of Granada , Granada , Spain
- c Biosanitary Institute of Granada (IBS GRANADA) , SAS -Universidad de Granada , Granada , Spain
| | - Antonio Láinez-Ramos-Bossini
- c Biosanitary Institute of Granada (IBS GRANADA) , SAS -Universidad de Granada , Granada , Spain
- d Department of Radiology , Hospital Universitario Virgen de las Nieves , Granada , Spain
| | - Raul Quesada
- a Department of Anatomy and Embryology, Faculty of Medicine , University of Granada , Granada , Spain
- b Institute of Biopathology and Regenerative Medicine (IBIMER), Biomedical Research Center (CIBM) , University of Granada , Granada , Spain
- c Biosanitary Institute of Granada (IBS GRANADA) , SAS -Universidad de Granada , Granada , Spain
| | - Gloria Perazzoli
- b Institute of Biopathology and Regenerative Medicine (IBIMER), Biomedical Research Center (CIBM) , University of Granada , Granada , Spain
| | - Pablo Alvarez
- b Institute of Biopathology and Regenerative Medicine (IBIMER), Biomedical Research Center (CIBM) , University of Granada , Granada , Spain
| | - Jose Prados
- a Department of Anatomy and Embryology, Faculty of Medicine , University of Granada , Granada , Spain
- b Institute of Biopathology and Regenerative Medicine (IBIMER), Biomedical Research Center (CIBM) , University of Granada , Granada , Spain
- c Biosanitary Institute of Granada (IBS GRANADA) , SAS -Universidad de Granada , Granada , Spain
| | - Consolación Melguizo
- a Department of Anatomy and Embryology, Faculty of Medicine , University of Granada , Granada , Spain
- b Institute of Biopathology and Regenerative Medicine (IBIMER), Biomedical Research Center (CIBM) , University of Granada , Granada , Spain
- c Biosanitary Institute of Granada (IBS GRANADA) , SAS -Universidad de Granada , Granada , Spain
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