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Comparison of the Chondrogenic Potential of Mesenchymal Stem Cells Derived from Bone Marrow and Umbilical Cord Blood Intended for Cartilage Tissue Engineering

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Abstract

Osteoarthritis (OA) remains incurable in humans or horses and mesenchymal stromal/stem cells (MSCs) represent an attractive solution for producing a neocartilage substitute. However, the best MSC source still needs to be identified. This study compared the chondrogenic potential of equine MSCs derived from bone marrow (BM) and umbilical cord blood (UCB), at their undifferentiated status to check if one cell source is better proned, and after chondrogenic-induced differentiation. Chondrogenesis was induced by culture in collagen scaffold with BMP-2 + TGF-ß1 in hypoxia or normoxia. MSCs chondrogenic potential was evaluated using the mRNA and corresponding protein levels for osteogenic, hypertrophic and chondrogenic markers. MSCs characterization demonstrated that BM- and UCB-MSCs differ in proliferation and tripotencies. At undifferentiated status, they also showed differences in their expression of osteogenic, chondrogenic and hypertrophic markers. Upon chondrogenesis induction, both MSCs sources exhibited increased chondrogenic expression and produce an extracellular matrix (ECM) of better quality in hypoxia, although collagen I remained expressed. UCB-MSCs produced higher amounts of collagen II, particularly its IIB isoform, than BM-MSCs, but also collagen I and Htra1, regardless of the oxygen condition. Finally, immunohistochemistry revealed that the BM-MSCs synthesized an ECM of higher quality, regarding the more homogenous distribution of type IIB collagen, compared to UCB-MSCs. Considering collagen I as the major undesirable component in the neo-synthesis of in vitro cartilage, we recommend using BM-MSCs for horse cartilage engineering.

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Acknowledgements

We are grateful to Marylin Guillamin for her help for flow cytometry analyses and to Marie-Christine Enos for her administrative and technical support.

Role of the Funding Sources

This research was funded by the French National Research Agency (ANR) and by the Regional Council of Basse-Normandie through the ANR TecSan PROMOCART program to P.G. (917RB020 and 917RB072 respectively), by the French Ministry of Research and Technology to PG, by three ERDF (European Regional Development Funds) grants to P.G. and M.D. (HIPPOCART 1 no. 2897/33535, 917RB148; HIPPOCART 917CB174, EQUISTEM 917CB210), by a Regional Council of Basse-Normandie program to PG and MD (HIPPOCART N° 2013-AGRI-236/13P07492, 917CB166), by Fonds Eperon to PG and MD (EQUISTEM, N80–2014, 917CB194), by the GIS CENTAURE-equine research (EQUISTEM-G program to PG, 014CJ061), by ERDF and Regional Council of Basse-Normandie grant to P.G. and M.D. in the CPER Centaure program (2015–2020, Centaure Biotechnologies 2015 N° 917CB213&Centaure PREACH 2016–17). CENTAURE is an European project co-funded by the Normandy County Council, European Union in the framework of the ERDF-ESF operational program 2014–2020. These funding sources had no involvement in the study design, collection, analysis, or in interpretation of the data, in the writing of the manuscript, or in the decision to submit the manuscript for publication.

RC was supported by a PhD scholarship co-financed by the Fonds Eperon and the Regional Council of Basse-Normandie, and TB by a PhD fellowship from the French Ministry of Research and Technology. MDes was recipient from a PhD fellowship from the Regional Council of Basse-Normandie. MC was supported by an ERASMUS program (ERASMUS center of Parma University, Italy).

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Authors and Affiliations

  1. UNICAEN, BIOTARGEN, Normandie University, 14000, Caen, France

    Romain Contentin, Magali Demoor, Miranda Concari, Mélanie Desancé, Thomas Branly & Philippe Galéra

  2. Center of Imaging and Research on Locomotor Affections in Equines, Ecole Vétérinaire d’Alfort, Université de Paris-Est, 14430, Goustranville, France

    Fabrice Audigié

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  1. Romain Contentin
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  2. Magali Demoor
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  3. Miranda Concari
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  4. Mélanie Desancé
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  6. Thomas Branly
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  7. Philippe Galéra
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Contributions

RC and TB were involved in study design, in data collection/assembly and analysis, and performed experiments. TB, RC, MD, MDes and FA were involved in collecting BM- and UCB-MSCs. MC and MDes performed experiments, collected and analysed the data. FA analysed the data. PG and MD were involved in study conception and design, in supervision of the study, in data analysis and interpretation, and provide the financial support. RC wrote the original draft and participated to the responses to the reviewers with PG. PG and TB were involved in writing-reviewing, realized the critical revision of the article and the final approval. All authors read and approved the final manuscript.

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Correspondence to Philippe Galéra.

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Contentin, R., Demoor, M., Concari, M. et al. Comparison of the Chondrogenic Potential of Mesenchymal Stem Cells Derived from Bone Marrow and Umbilical Cord Blood Intended for Cartilage Tissue Engineering. Stem Cell Rev and Rep 16, 126–143 (2020). https://doi.org/10.1007/s12015-019-09914-2

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