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Int. J. Mol. Sci. 2017, 18(9), 1933; doi:10.3390/ijms18091933

Hypoxia Is a Critical Parameter for Chondrogenic Differentiation of Human Umbilical Cord Blood Mesenchymal Stem Cells in Type I/III Collagen Sponges

1
Normandie Université, Université de Caen Normandie, Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT), équipe Microenvironnement des Pathologies Dégénératives et Fibrotiques (MIPDF), EA 4652/BIOTARGEN EA 7450, UFR Santé, 14032 Caen, France
2
Service de Gynécologie-Obstétrique et Médecine de la Reproduction, CHU Caen, 14033 Caen, France
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 18 July 2017 / Revised: 29 August 2017 / Accepted: 1 September 2017 / Published: 8 September 2017
(This article belongs to the Special Issue Musculoskeletal Diseases Therapy)
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Abstract

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-β (TGF-β1)) 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% O2) or hypoxia (<5% O2) for 7, 14 and 21 days. Our results show that UCB-MSCs can be committed to chondrogenesis in the presence of BMP-2+TGF-β1. 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. View Full-Text
Keywords: mesenchymal stem cells; umbilical cord blood; cartilage tissue engineering; hypoxia; chondrogenesis mesenchymal stem cells; umbilical cord blood; cartilage tissue engineering; hypoxia; chondrogenesis
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Gómez-Leduc, T.; Desancé, M.; Hervieu, M.; Legendre, F.; Ollitrault, D.; de Vienne, C.; Herlicoviez, M.; Galéra, P.; Demoor, M. Hypoxia Is a Critical Parameter for Chondrogenic Differentiation of Human Umbilical Cord Blood Mesenchymal Stem Cells in Type I/III Collagen Sponges. Int. J. Mol. Sci. 2017, 18, 1933.

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