Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 18, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/ijms18091933
Keywords
mesenchymal stem cells; umbilical cord blood; cartilage tissue engineering; hypoxia; chondrogenesis
Funding
- French National Research Agency (ANR)
- Regional Council of Basse-Normandie [917RB020, 917RB072]
- French Ministry of Research and Technology
- ERDF (European Regional Development Funds) [HIPPOCART 1, 2897/33535, 917RB148, HIPPOCART 917CB174]
- Regional Council of Basse-Normandie program [2013-AGRI-236/13P07492, 917CB166]
- Fonds Eperon [N80-2014, 917CB194]
- Regional Council of Basse-Normandie
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Umbilical cord blood (UCB) is an attractive alternative to bone marrow for isolation of mesenchymal stem cells (MSCs) to treat articular cartilage defects. Here, we set out to determine the growth factors (bone morphogenetic protein 2 (BMP-2) and transforming growth factor- (TGF-1)) and oxygen tension effects during chondrogenesis of human UCB-MSCs for cartilage engineering. Chondrogenic differentiation was induced using 3D cultures in type I/III collagen sponges with chondrogenic factors in normoxia (21% O-2) or hypoxia (<5% O-2) for 7, 14 and 21 days. Our results show that UCB-MSCs can be committed to chondrogenesis in the presence of BMP-2+TGF-1. Normoxia induced the highest levels of chondrocyte-specific markers. However, hypoxia exerted more benefit by decreasing collagen X and matrix metalloproteinase-13 (MMP13) expression, two chondrocyte hypertrophy markers. However, a better chondrogenesis was obtained by switching oxygen conditions, with seven days in normoxia followed by 14 days in hypoxia, since these conditions avoid hypertrophy of hUCB-MSC-derived chondrocytes while maintaining the expression of chondrocyte-specific markers observed in normoxia. Our study demonstrates that oxygen tension is a key factor for chondrogenesis and suggests that UBC-MSCs 3D-culture should begin in normoxia to obtain a more efficient chondrocyte differentiation before placing them in hypoxia for chondrocyte phenotype stabilization. UCB-MSCs are therefore a reliable source for cartilage engineering.
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