Osteoarthritic chondrocyte-secreted morphogens induce chondrogenic differentiation of human mesenchymal stem cells.
Osteoarthritic chondrocyte-secreted morphogens induce chondrogenic differentiation of human mesenchymal stem cells.
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DOI:
10.1002/art.30086
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发表时间:
2011-01
影响因子:
--
通讯作者:
Varghese, Shyni
中科院分区:
文献类型:
--
作者:
Aung, Aereas;Gupta, Gunjan;Majid, Ghassemian;Varghese, Shyni
The potential of stem cells to repair compromised cartilage tissues such as in osteoarthritis (OA) depends strongly on how transplanted cells respond to factors secreted from the residing OA chondrocytes. This study determines the effect of morphogenetic signals from OA chondrocytes on chondrogenic differentiation of human mesenchymal stem cells (hMSCs). Effect of OA chondrocyte secreted morphogens on chondrogenic differentiation of hMSCs was evaluated using a co-culture system involving both primary and passaged OA chondrocytes. The findings were compared against hMSCs cultured in OA chondrocytes conditioned medium. Gene expression, biochemical assays, and immunofluorescent staining were used to characterize the chondrogenic differentiation of hMSCs. Mass spectrometry analysis was used to identify the soluble factors. Numerical analysis was carried out to model the concentration profile of soluble factors within the hMSC-laden hydrogels. The hMSCs co-cultured with primary OA chondrocytes underwent chondrogenic differentiation even in the absence of growth factors; however the same effect could not be mimicked using OA chondrocytes conditioned medium or expanded cells. Additionally, the co-cultured environment down-regulated hypertrophic differentiation of hMSCs. Mass spectrometry analysis demonstrates cell-cell communication and chondrocyte phenotype-dependent effects on cell-secreted morphogens. The experimental findings along with the numerical analysis suggest a crucial role of soluble morphogens and their local concentrations on the differentiation pattern of hMSCs in a three-dimensional environment. This concept of utilizing a small number of chondrocytes to promote chondrogenic differentiation of hMSCs while preventing their hypertrophic differentiation could be of great of importance in formulating effective stem cell-based cartilage repair.
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影响因子:
--
作者:
Chen, Wei-Hong;Lai, Ming-Tang;Deng, Win-Ping
通讯作者:
Deng, Win-Ping
影响因子:
5.6
作者:
Hwang, Nathaniel S.;Varghese, Shyni;Elisseeff, Jennifer
通讯作者:
Elisseeff, Jennifer
DOI:
10.1016/0304-4165(86)90306-5
发表时间:
1986-09-04
期刊:
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子:
--
作者:
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者:
BARRETT, AJ
影响因子:
4.9
作者:
Grogan SP;Miyaki S;Asahara H;D'Lima DD;Lotz MK
通讯作者:
Lotz MK
DOI:
10.1073/pnas.0608660104
发表时间:
2007-04-03
影响因子:
11.1
作者:
Hui, Elliot E.;Bhatia, Sangeeta N.
通讯作者:
Bhatia, Sangeeta N.