Abstract
To investigate the functional effects of resveratrol (RSV) on mesenchymal stem cells (MSCs), we treated MSCs with RSV continuously during ex vivo expansion. MSCs were continuously treated with RSV from passage (P) 0 to P5. A proliferative capacity of RSV-treated MSCs was higher than that of non-treated MSCs and similar with P1-MSCs. Continuous treatment of RSV on MSCs increased the stemness and inhibited the senescence. During chondrogenic differentiation in vitro, RSV-treated MSCs had higher differentiation potential and reduced hypertrophic maturation, which are limitations for hyaline cartilage formation. The histological analysis of micromass demonstrated increased chondrogenic differentiation potential. We further explored the therapeutic effectiveness of this method in a rabbit osteochondral defect model. A rabbit osteochondral defect model was established to investigate the hyaline cartilage regeneration potential of RSV-treated MSCs. Moreover, the cartilage regeneration potential of RSV-treated MSCs was greater than that of untreated MSCs. The expression levels of chondrogenic markers increased and those of hypertrophic markers decreased in RSV-treated MSCs compared with untreated MSCs. Sustained treatment of RSV on MSCs during ex vivo expansion resulted in the maintenance of stemness and enhanced chondrogenic differentiation potential. Consequentially, highly efficient MSCs promoted superior hyaline cartilage regeneration in vivo. This novel treatment method provides a basis for cell-based tissue engineering.
Highlights
Osteoarthritis (OA) involves cartilage damage, dysfunctional chondrocyte proliferation, and hypertrophic maturation[1,2,3,4]
In P5RMSCs, the stemness markers were up-regulated and senescence markers were down-regulated, similar to the expression levels in P1-mesenchymal stem cells (MSCs), the opposite results were obtained for P5-MSCs, which exhibited the upregulation of senescence markers and down-regulation of stemness markers (Fig. 1d, e)
As shown in our previous study, the maintenance of sirtuin 1 (SIRT1) activity sustains the expression of SOX237; the stemness of MSCs could be maintained over time
Summary
Osteoarthritis (OA) involves cartilage damage, dysfunctional chondrocyte proliferation, and hypertrophic maturation[1,2,3,4]. Several types of therapies are currently used for cartilage regeneration, including bone marrowstimulating techniques, mosaicplasty, and cell-based therapies[5]. Autologous chondrocyte implantation is commonly used for cartilage regeneration, requiring the in vitro expansion of autologous chondrocytes[6]. These techniques have several shortcomings, such as their complexity, cost, and the loss of cartilage capacity[7,8]. Cell-based therapeutic approaches using mesenchymal stem cells (MSCs) have emerged for cartilage regeneration[9,10,11]
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