Enhanced chondrogenesis of bone marrow-derived stem cells by using a combinatory cell therapy strategy with BMP-2/TGF-β1, hypoxia, and COL1A1/HtrA1 siRNAs
Abstract Mesenchymal stem cells (MSCs) hold promise for cartilage engineering. Here, we aimed to determine the best culture conditions to induce chondrogenesis of MSCs isolated from bone marrow (BM) of aged osteoarthritis (OA) patients. We showed that these BM-MSCs proliferate slowly, are not unifor...
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Nature Portfolio
2017
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oai:doaj.org-article:82d6b1bbe1f74d39bee2a4236a55d4f92021-12-02T12:32:38ZEnhanced chondrogenesis of bone marrow-derived stem cells by using a combinatory cell therapy strategy with BMP-2/TGF-β1, hypoxia, and COL1A1/HtrA1 siRNAs10.1038/s41598-017-03579-y2045-2322https://doaj.org/article/82d6b1bbe1f74d39bee2a4236a55d4f92017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03579-yhttps://doaj.org/toc/2045-2322Abstract Mesenchymal stem cells (MSCs) hold promise for cartilage engineering. Here, we aimed to determine the best culture conditions to induce chondrogenesis of MSCs isolated from bone marrow (BM) of aged osteoarthritis (OA) patients. We showed that these BM-MSCs proliferate slowly, are not uniformly positive for stem cell markers, and maintain their multilineage potential throughout multiple passages. The chondrogenic lineage of BM-MSCs was induced in collagen scaffolds, under normoxia or hypoxia, by BMP-2 and/or TGF-β1. The best chondrogenic induction, with the least hypertrophic induction, was obtained with the combination of BMP-2 and TGF-β1 under hypoxia. Differentiated BM-MSCs were then transfected with siRNAs targeting two markers overexpressed in OA chondrocytes, type I collagen and/or HtrA1 protease. siRNAs significantly decreased mRNA and protein levels of type I collagen and HtrA1, resulting in a more typical chondrocyte phenotype, but with frequent calcification of the subcutaneously implanted constructs in a nude mouse model. Our 3D culture model with BMP-2/TGF-β1 and COL1A1/HtrA1 siRNAs was not effective in producing a cartilage-like matrix in vivo. Further optimization is needed to stabilize the chondrocyte phenotype of differentiated BM-MSCs. Nevertheless, this study offers the opportunity to develop a combinatory cellular therapy strategy for cartilage tissue engineering.Florence LegendreDavid OllitraultTangni Gomez-LeducMouloud BouyoucefMagalie HervieuNicolas GruchyFrédéric Mallein-GerinSylvain LeclercqMagali DemoorPhilippe GaléraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017) |
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Medicine R Science Q Florence Legendre David Ollitrault Tangni Gomez-Leduc Mouloud Bouyoucef Magalie Hervieu Nicolas Gruchy Frédéric Mallein-Gerin Sylvain Leclercq Magali Demoor Philippe Galéra Enhanced chondrogenesis of bone marrow-derived stem cells by using a combinatory cell therapy strategy with BMP-2/TGF-β1, hypoxia, and COL1A1/HtrA1 siRNAs |
| description |
Abstract Mesenchymal stem cells (MSCs) hold promise for cartilage engineering. Here, we aimed to determine the best culture conditions to induce chondrogenesis of MSCs isolated from bone marrow (BM) of aged osteoarthritis (OA) patients. We showed that these BM-MSCs proliferate slowly, are not uniformly positive for stem cell markers, and maintain their multilineage potential throughout multiple passages. The chondrogenic lineage of BM-MSCs was induced in collagen scaffolds, under normoxia or hypoxia, by BMP-2 and/or TGF-β1. The best chondrogenic induction, with the least hypertrophic induction, was obtained with the combination of BMP-2 and TGF-β1 under hypoxia. Differentiated BM-MSCs were then transfected with siRNAs targeting two markers overexpressed in OA chondrocytes, type I collagen and/or HtrA1 protease. siRNAs significantly decreased mRNA and protein levels of type I collagen and HtrA1, resulting in a more typical chondrocyte phenotype, but with frequent calcification of the subcutaneously implanted constructs in a nude mouse model. Our 3D culture model with BMP-2/TGF-β1 and COL1A1/HtrA1 siRNAs was not effective in producing a cartilage-like matrix in vivo. Further optimization is needed to stabilize the chondrocyte phenotype of differentiated BM-MSCs. Nevertheless, this study offers the opportunity to develop a combinatory cellular therapy strategy for cartilage tissue engineering. |
| format |
article |
| author |
Florence Legendre David Ollitrault Tangni Gomez-Leduc Mouloud Bouyoucef Magalie Hervieu Nicolas Gruchy Frédéric Mallein-Gerin Sylvain Leclercq Magali Demoor Philippe Galéra |
| author_facet |
Florence Legendre David Ollitrault Tangni Gomez-Leduc Mouloud Bouyoucef Magalie Hervieu Nicolas Gruchy Frédéric Mallein-Gerin Sylvain Leclercq Magali Demoor Philippe Galéra |
| author_sort |
Florence Legendre |
| title |
Enhanced chondrogenesis of bone marrow-derived stem cells by using a combinatory cell therapy strategy with BMP-2/TGF-β1, hypoxia, and COL1A1/HtrA1 siRNAs |
| title_short |
Enhanced chondrogenesis of bone marrow-derived stem cells by using a combinatory cell therapy strategy with BMP-2/TGF-β1, hypoxia, and COL1A1/HtrA1 siRNAs |
| title_full |
Enhanced chondrogenesis of bone marrow-derived stem cells by using a combinatory cell therapy strategy with BMP-2/TGF-β1, hypoxia, and COL1A1/HtrA1 siRNAs |
| title_fullStr |
Enhanced chondrogenesis of bone marrow-derived stem cells by using a combinatory cell therapy strategy with BMP-2/TGF-β1, hypoxia, and COL1A1/HtrA1 siRNAs |
| title_full_unstemmed |
Enhanced chondrogenesis of bone marrow-derived stem cells by using a combinatory cell therapy strategy with BMP-2/TGF-β1, hypoxia, and COL1A1/HtrA1 siRNAs |
| title_sort |
enhanced chondrogenesis of bone marrow-derived stem cells by using a combinatory cell therapy strategy with bmp-2/tgf-β1, hypoxia, and col1a1/htra1 sirnas |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/82d6b1bbe1f74d39bee2a4236a55d4f9 |
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