Abstract
With the rapidly growing demand for mesenchymal stem cell (MSC) therapy, numerous strategies using MSCs for different diseases have been studied and reported. Because of their immunosuppressive properties, MSCs are commonly used as an allogeneic treatment. However, for the many donors who could potentially be used, it is important to understand the capacity for therapeutic usage with donor-to-donor heterogeneity. In this study, we aimed to investigate MSCs as a promising therapeutic strategy for critical limb ischemia. We evaluated MSCs from two donors (#55 and #64) and analyzed the capacity for angiogenesis through in vivo and in vitro assays to compare the therapeutic effect between different donors. We emphasized the importance of intra-population heterogeneity of MSCs on therapeutic usage by evaluating the effects of hypoxia on activating cellular angiogenesis in MSCs. The precondition of hypoxia in MSCs is known to enhance therapeutic efficacy. Our study suggests that sensitivity to hypoxic conditions is different between cells originating from different donors, and this difference affects the contribution to angiogenesis. The bioinformatics analysis of different donors under hypoxic culture conditions identified intrinsic variability in gene expression patterns and suggests alternative potential genetic factors ANGPTL4, ADM, SLC2A3, and CDON as guaranteed general indicators for further stem cell therapy.
Highlights
With the rapidly growing demand for mesenchymal stem cell (MSC) therapy, numerous strategies using Mesenchymal stem cells (MSCs) for different diseases have been studied and reported
To confirm the hypoxic conditions, we first examined the enhanced expression of HIF-1α in the nucleus of the hUCB-MSCs when cultured at a low-oxygen level (O2 1%) (Fig. 1a)
Discussion a number of studies has reported that hypoxic preconditioning increases therapeutic potential and the cellular functions of mesenchymal stem cells, including differentiation, motility, and vascular forming capacity, these studies recruited their own experimental conditions, such as the hypoxia concentrations and exposure times[18,19,22,26]
Summary
With the rapidly growing demand for mesenchymal stem cell (MSC) therapy, numerous strategies using MSCs for different diseases have been studied and reported. Recent studies have focused on modifying MSCs to improve revascularization and understand the cell’s biological role and mode of action in angiogenesis[10] Despite these efforts and accomplishments, the results of current preclinical studies and clinical trials suggest that a better alleviation strategy with MSC therapy is still needed. To verify MSCs as a reliable cell source and establish MSC cell therapy for PAD, the strikingly variable behaviors among MSCs isolated from different donors must be understood Recent studies addressing this issue have compared bone marrow MSCs from various donors and found significant differences in cell growth rates and alkaline phosphatase enzyme activity[12]. Differentiation capacity showed contrasting results between cells from different donors, with distinguished osteogenic differentiation ability with different gene levels, and the adipocyte-specific gene expression varied as well[13]
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