Simulated microgravity affects chondrogenesis and hypertrophy of human mesenchymal stem cells

Mayer-Wagner, Susanne, Hammerschmid, Florian, Redeker, Julia I., Schmitt, Bärbel, Holzapfel, Boris Michael, Jansson, Volkmar, Betz, Oliver B., & Müller, Peter E. (2014) Simulated microgravity affects chondrogenesis and hypertrophy of human mesenchymal stem cells. International Orthopaedics, 38(12), pp. 2615-2621.

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Abstract

Purpose

During in vitro chondrogenesis of human mesenchymal stem cells (hMSCs) hypertrophy is an inadvertent event associated with cell differentiation toward the osteogenic lineage. Up to now, there is no stringent experimental control mechanism to prevent hypertrophy of MSCs. Microgravity is known to have an impact on osteogenesis. In this study, the influence of simulated microgravity (SMG) on both chondrogenesis and hypertrophy of hMSCs was evaluated.

Methods

A bioreactor using a rotating wall vessel was constructed to simulate microgravity. Pellet cultures formed from hMSCs (P5) were supplemented with human transforming growth factor-β3 (TGF-β3). The hMSC pellet cultures treated with TGF-β3 were either kept in SMG or in a control system. After three weeks of culture, the chondrogenic differentiation status and level of hypertrophy were examined by safranin-O staining, immunohistochemistry and quantitative real-time PCR.

Results

SMG reduced the staining for safranin-O and collagen type II. The expression of collagen type X α1 chain (COL10A1) and collagen type II α1 chain (COL2A1) were both significantly reduced. There was a higher decrease in COL2A1 than in COL10A1 expression, resulting in a low COL2A1/COL10A1 ratio.

Conclusions

SMG reduced hypertrophy of hMSCs during chondrogenic differentiation. However, the expression of COL2A1 was likewise reduced. Even more, the COL2A1/COL10A1 ratio decreased under SMG conditions. We therefore assume that SMG has a significant impact on the chondrogenic differentiation of hMSCs. However, due to the high COL2A1 suppression under SMG, this culture system does not yet seem to be suitable for a potential application in cartilage repair.

Impact and interest:

1 citations in Scopus
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1 citations in Web of Science®

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ID Code: 88646
Item Type: Journal Article
Refereed: Yes
Keywords: Simulated microgravity, Mesenchymal stem cells, Chondrogenic differentiation, Hypertrophy, Cartilage repair, Transforming growth factor-β3
DOI: 10.1007/s00264-014-2454-3
ISSN: 0341-2695
Deposited On: 04 Nov 2015 00:30
Last Modified: 04 Nov 2015 00:30

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