Resveratrol Effect on Adipose-Derived Stem Cells Differentiation to Chondrocyte in Three-Dimensional Culture

Abstract

Purpose: Adipose stem cells (ASCs) are pluripotent cells with the ability of self-renewal and differentiation into different types of mesenchymal cells. As cartilage repair is difficult due to lack of blood capillary, resveratrol (Res) is a polyphenolic compound with diverse biological properties to be possibly used in this case. The aim of the present study was to investigate the effect of Res on differentiation of ASCs into chondrocyte in a three-dimensional (3D) culture model. Methods: Subcutaneous adipose tissues were prepared and digested enzymatically, and passed through cell strainer. ASCs were harvested in the fourth passage, and divided into five groups. The control group received chondrogenic differentiation medium (CDM) while the experimental groups received CDM plus different doses of Res (1, 10, 20, and 50 µM) for 21 days. Expression of cartilage specific genes and Sirtuin1 (SIRT 1), cell viability, apoptosis and ferric reducing antioxidant power (FRAP) were detected using reverse transcription polymerase chain reaction (RT-PCR), MTT assay, TUNEL and acridine orange/ethidium bromide (AO/EB) staining. One-way ANOVA and non-parametric Mann-Whitney U test were used for data analyses. Results: ASCs were differentiated to chondrocyte by CDM in a three-dimensional culture. 10 and 20 µM doses of Res showed the most proliferating effect on ADSCs. The SIRT 1 genes expression and FRAP level also increased significantly compared to the control group (P<0.05). Also, OD of cell increased whereas apoptosis decreased. Conclusion: 3D culture was a suitable condition for ASCs differentiation to chondrocyte, and lower doses of Res exert proliferation effect on ASCs.

Repair of articular cartilage defect using adipose‐derived stem cell‐loaded scaffold derived from native cartilage extracellular matrix

“…Moreover, many researchers have successfully induced chondrogenic differentiation of ADSCs in vitro and in vivo (Goudarzi et al, 2018;Hwang, Noh, Hong, & Lee, 2020;Yang, Chen, Yang, Hsiao, & Wang, 2020). And in the field of cartilage tissue engineering, an increasing number of studies have confirmed that adipose stem cells have good chondrogenic differentiation ability, which is comparable to bone marrow stromal stem cells (Chung et al, 2019;Keshavarz, Jalili, Pazhouhi, & Khazaei, 2019;Nguyen, Doan, & Tran, 2019). Therefore, ADSCs are cartilage tissue engineering seed cells, with rare advantages and prospects.…”

Pharmaceutical therapeutics for articular regeneration and restoration: state-of-the-art technology for screening small molecular drugs

“…Heck et al reported that GW0742, a PPAR-δ agonist, enhanced human MSC chondrogenesis and alleviated cartilage fibrosis/inflammation in an in vitro model by stimulating type II collagen/glycosaminoglycan secretion [ 29 ]. As Sirtuin-1 (SIRT1) is required for stem cell chondrogenesis, the SIRT1 activator resveratrol partially inhibits the inflammatory effect of IL-1β on human MSC differentiation in vitro [ 30 ] and promotes human ADSC proliferation in a three-dimensional chondrogenic culture [ 31 ]. The small molecule BIO (6-bromoindirubin-3-oxim) inhibits glycogen synthase kinase-3 (GSK-3) in the Wnt pathway and can upregulate cartilage-specific genes in mouse MSC in in vitro chondrogenesis [ 32 ].…”

Resveratrol’s Impact on the Chondrogenic Reagents’ Effects in Cell Sheet Cultures of Wharton’s Jelly-Derived MSCs

“…Among the targets of resveratrol, sirtuin 1 (SIRT1), adenosine monophosphate activated protein kinase (AMPK), and cyclooxygenase-2 are primarily noted [22]. For BM-MSCs [23], adipose MSCs [24,25], and WJ-MSCs, resveratrol improves the proliferation and further chondrogenic differentiation, as assessed by the expression of chondrogenic markers such as Sox9, collagen type II, and aggrecan.…”