Abstract
Mesenchymal stem cells (MSCs) have a variety of unique properties, such as stem cell multipotency and immune regulation, making them attractive for use in cell therapy. Before infusion therapy, MSCs are required to undergo tissue separation, purification, and expansion in vitro for a certain duration. During the process of in vitro expansion of MSCs, the influence of culture time and environment can lead to cell senescence, increased heterogeneity, and function attenuation, which limits their clinical applications. We used a cocktail of three small-molecule compounds, ACY (A-83–01, CHIR99021, and Y-27632), to increase the proliferation activity of MSCs in vitro and reduce cell senescence. ACY inhibited the increase in heterogeneity of MSCs and conserved their differentiation potential. Additionally, ACY maintained the phenotype of MSCs and upregulated the expression of immunomodulatory factors. These results suggest that ACY can effectively improve the quantity and quality of MSCs.
Highlights
Mesenchymal stem cells (MSCs) have considerable application potential in the field of regenerative medicine due to their low immunogenicity, immunomodulatory, and self-renewal properties (Han et al, 2019)
We developed a cocktail of three small-molecule compounds (A-83–01, CHIR99021, and Y-27632; ACY) to enhance the growth of MSCs and tested the function by evaluating the impact of this cocktail on cell viability and phenotypic properties of MSCs in cell culture
Many reports suggest that TGF-β stimulation can promote the proliferation and prevent apoptosis of MSCs (Stewart et al, 2010; Walenda et al, 2013; Gurung et al, 2020), and other studies have shown that activation of the TGF-β pathway can cause cell senescence (Ito et al, 2007; Gurung et al, 2020)
Summary
Mesenchymal stem cells (MSCs) have considerable application potential in the field of regenerative medicine due to their low immunogenicity, immunomodulatory, and self-renewal properties (Han et al, 2019). The number of freshly isolated cells is insufficient for clinical applications. Increases in cell culture generations and various influential factors in the culture environment, such as chemical compounds, radiation, and oxidative stress, can cause MSCs to become senescent and change their phenotype (Banimohamad-Shotorbani et al, 2020). Many studies have shown that it is challenging for MSCs to maintain stable therapeutic effects in clinical applications due to many non-directional changes in cellular characteristics and the upregulation of heterogeneity during the expansion process (Guo et al, 2006; Levy et al, 2020; Yin et al, 2019). There is a critical need for the development of MSC culture systems that reduce cell senescence and maintain long-term growth viability and cell homogeneity
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