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

Abstract

AimsCombining 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.MethodshAMSCs 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.ResultsThe 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.ConclusionsThis 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.

Human iPSCs can be differentiated into notochordal cells that reduce intervertebral disc degeneration in a porcine model

“…3). There are reports that show paracrine effect of MSCs in promoting cartilage formation by articular chondrocytes when co-cultured with MSCs 80. However, the data shown in Figure 5 indicate that iNC-conditioned media had direct effect on MSCs, strengthening the conclusion that the MSCs were affected by iNCs and not the opposite.…”

Characterization of the iPSC-derived conditioned medium that promotes the growth of bovine corneal endothelial cells

“…In this study, the species mismatch limits the translation of the presented basic research to clinical application. However, the species mismatch was chosen to be able to discriminate between the role of the different cell types (Pleumeekers et al, 2018). The limited proliferative ability of HCECs makes the in vitro propagation of CECs difficult, while B-CECs are relatively easy to obtain.…”

Bioinspired materials and tissue engineering approaches applied to the regeneration of musculoskeletal tissues

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