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Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration
INTRODUCTION: Adipose stem cells (ASCs) secrete many trophic factors that can stimulate tissue repair, including angiogenic factors, but little is known about how ASCs and their secreted factors influence cartilage regeneration. Therefore, the aim of this study was to determine the effects ASC-secre...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580473/ https://www.ncbi.nlm.nih.gov/pubmed/22920724 http://dx.doi.org/10.1186/scrt126 |
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author | Lee, Christopher SD Burnsed, Olivia A Raghuram, Vineeth Kalisvaart, Jonathan Boyan, Barbara D Schwartz, Zvi |
author_facet | Lee, Christopher SD Burnsed, Olivia A Raghuram, Vineeth Kalisvaart, Jonathan Boyan, Barbara D Schwartz, Zvi |
author_sort | Lee, Christopher SD |
collection | PubMed |
description | INTRODUCTION: Adipose stem cells (ASCs) secrete many trophic factors that can stimulate tissue repair, including angiogenic factors, but little is known about how ASCs and their secreted factors influence cartilage regeneration. Therefore, the aim of this study was to determine the effects ASC-secreted factors have in repairing chondral defects. METHODS: ASCs isolated from male Sprague Dawley rats were cultured in monolayer or alginate microbeads supplemented with growth (GM) or chondrogenic medium (CM). Subsequent co-culture, conditioned media, and in vivo cartilage defect studies were performed. RESULTS: ASC monolayers and microbeads cultured in CM had decreased FGF-2 gene expression and VEGF-A secretion compared to ASCs cultured in GM. Chondrocytes co-cultured with GM-cultured ASCs for 7 days had decreased mRNAs for col2, comp, and runx2. Chondrocytes treated for 12 or 24 hours with conditioned medium from GM-cultured ASCs had reduced sox9, acan, and col2 mRNAs; reduced proliferation and proteoglycan synthesis; and increased apoptosis. ASC-conditioned medium also increased endothelial cell tube lengthening whereas conditioned medium from CM-cultured ASCs had no effect. Treating ASCs with CM reduced or abolished these deleterious effects while adding a neutralizing antibody for VEGF-A eliminated ASC-conditioned medium induced chondrocyte apoptosis and restored proteoglycan synthesis. FGF-2 also mitigated the deleterious effects VEGF-A had on chondrocyte apoptosis and phenotype. When GM-grown ASC pellets were implanted in 1 mm non-critical hyaline cartilage defects in vivo, cartilage regeneration was inhibited as evaluated by radiographic and equilibrium partitioning of an ionic contrast agent via microCT imaging. Histology revealed that defects with GM-cultured ASCs had no tissue ingrowth from the edges of the defect whereas empty defects and defects with CM-grown ASCs had similar amounts of neocartilage formation. CONCLUSIONS: ASCs must be treated to reduce the secretion of VEGF-A and other factors that inhibit cartilage regeneration, which can significantly influence how ASCs are used for repairing hyaline cartilage. |
format | Online Article Text |
id | pubmed-3580473 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35804732013-02-26 Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration Lee, Christopher SD Burnsed, Olivia A Raghuram, Vineeth Kalisvaart, Jonathan Boyan, Barbara D Schwartz, Zvi Stem Cell Res Ther Research INTRODUCTION: Adipose stem cells (ASCs) secrete many trophic factors that can stimulate tissue repair, including angiogenic factors, but little is known about how ASCs and their secreted factors influence cartilage regeneration. Therefore, the aim of this study was to determine the effects ASC-secreted factors have in repairing chondral defects. METHODS: ASCs isolated from male Sprague Dawley rats were cultured in monolayer or alginate microbeads supplemented with growth (GM) or chondrogenic medium (CM). Subsequent co-culture, conditioned media, and in vivo cartilage defect studies were performed. RESULTS: ASC monolayers and microbeads cultured in CM had decreased FGF-2 gene expression and VEGF-A secretion compared to ASCs cultured in GM. Chondrocytes co-cultured with GM-cultured ASCs for 7 days had decreased mRNAs for col2, comp, and runx2. Chondrocytes treated for 12 or 24 hours with conditioned medium from GM-cultured ASCs had reduced sox9, acan, and col2 mRNAs; reduced proliferation and proteoglycan synthesis; and increased apoptosis. ASC-conditioned medium also increased endothelial cell tube lengthening whereas conditioned medium from CM-cultured ASCs had no effect. Treating ASCs with CM reduced or abolished these deleterious effects while adding a neutralizing antibody for VEGF-A eliminated ASC-conditioned medium induced chondrocyte apoptosis and restored proteoglycan synthesis. FGF-2 also mitigated the deleterious effects VEGF-A had on chondrocyte apoptosis and phenotype. When GM-grown ASC pellets were implanted in 1 mm non-critical hyaline cartilage defects in vivo, cartilage regeneration was inhibited as evaluated by radiographic and equilibrium partitioning of an ionic contrast agent via microCT imaging. Histology revealed that defects with GM-cultured ASCs had no tissue ingrowth from the edges of the defect whereas empty defects and defects with CM-grown ASCs had similar amounts of neocartilage formation. CONCLUSIONS: ASCs must be treated to reduce the secretion of VEGF-A and other factors that inhibit cartilage regeneration, which can significantly influence how ASCs are used for repairing hyaline cartilage. BioMed Central 2012-08-24 /pmc/articles/PMC3580473/ /pubmed/22920724 http://dx.doi.org/10.1186/scrt126 Text en Copyright ©2012 Lee et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Lee, Christopher SD Burnsed, Olivia A Raghuram, Vineeth Kalisvaart, Jonathan Boyan, Barbara D Schwartz, Zvi Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration |
title | Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration |
title_full | Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration |
title_fullStr | Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration |
title_full_unstemmed | Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration |
title_short | Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration |
title_sort | adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580473/ https://www.ncbi.nlm.nih.gov/pubmed/22920724 http://dx.doi.org/10.1186/scrt126 |
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