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Trophic effects of adipose-tissue-derived and bone-marrow-derived mesenchymal stem cells enhance cartilage generation by chondrocytes in co-culture


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Pleumeekers, MM, Nimeskern, L, Koevoet, JLM, Karperien, M, Stok, KS and van Osch, GJVM 2018 , 'Trophic effects of adipose-tissue-derived and bone-marrow-derived mesenchymal stem cells enhance cartilage generation by chondrocytes in co-culture' , PLoS ONE, vol. 13, no. 2 , e0190744 , doi: 10.1371/journal.pone.0190744.

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Aims:Combining mesenchymal stem cells (MSCs) and chondrocytes has great potential for cell-based cartilage repair. However, there is much debate regarding the mechanisms behind this concept. We aimed to clarify the mechanisms that lead to chondrogenesis (chondrocyte driven MSC-differentiation versus MSC driven chondroinduction) and whether their effect was dependent on MSC-origin. Therefore, chondrogenesis of human adipose-tissue-derived MSCs (hAMSCs) and bone-marrow-derived MSCs (hBMSCs) combined with bovine articular chondrocytes (bACs) was compared.Methods:hAMSCs or hBMSCs were combined with bACs in alginate and cultured in vitro or implanted subcutaneously in mice. Cartilage formation was evaluated with biochemical, histological and biomechanical analyses. To further investigate the interactions between bACs and hMSCs, (1) co-culture, (2) pellet, (3) Transwell® and (4) conditioned media studies were conducted.Results:The presence of hMSCs–either hAMSCs or hBMSCs—increased chondrogenesis in culture; deposition of GAG was most evidently enhanced in hBMSC/bACs. This effect was similar when hMSCs and bAC were combined in pellet culture, in alginate culture or when conditioned media of hMSCs were used on bAC. Species-specific gene-expression analyses demonstrated that aggrecan was expressed by bACs only, indicating a predominantly trophic role for hMSCs. Collagen-10-gene expression of bACs was not affected by hBMSCs, but slightly enhanced by hAMSCs. After in-vivo implantation, hAMSC/bACs and hBMSC/bACs had similar cartilage matrix production, both appeared stable and did not calcify.Conclusions:This study demonstrates that replacing 80% of bACs by either hAMSCs or hBMSCs does not influence cartilage matrix production or stability. The remaining chondrocytes produce more matrix due to trophic factors produced by hMSCs.

Item Type: Article
Authors/Creators:Pleumeekers, MM and Nimeskern, L and Koevoet, JLM and Karperien, M and Stok, KS and van Osch, GJVM
Keywords: combining mesenchymal stem cells, cell-based cartilage repair, hAMSCs, hBMSCs
Journal or Publication Title: PLoS ONE
Publisher: Public Library of Science
ISSN: 1932-6203
DOI / ID Number: 10.1371/journal.pone.0190744
Copyright Information:

Copyright 2018 Pleumeekers et al. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

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