Department of Biomedical Science, CHA University, Seongnam 13488, Gyunggi-do, Korea.
CHA Advanced Research Institute, CHA University, Seongnam 13488, Gyunggi-do, Korea.
Cells. 2021 May 24;10(6):1301. doi: 10.3390/cells10061301.
Mesenchymal progenitor cells (MPCs) are a promising cell source for regenerative medicine because of their immunomodulatory properties, anti-inflammatory molecule secretion, and replacement of damaged cells. Despite these advantages, heterogeneity in functional potential and limited proliferation capacity of MPCs, as well as the lack of suitable markers for product potency, hamper the development of large-scale manufacturing processes of MPCs. Therefore, there is a sustained need to develop highly proliferative and standardized MPCs in vitro and find suitable functional markers for measuring product potency. In this study, three lines of pluripotent stem cell (PSC)-derived MPCs with high proliferative ability were established and compared with bone-marrow-derived MPCs using proliferation assays and microarrays. A total of six genes were significantly overexpressed (>10-fold) in the highest proliferative MPC line (CHA-hNT5-MPCs) and validated by qRT-PCR. However, only two of the genes (MYOCD and ODZ2) demonstrated a significant correlation with MPC senescence in vitro. Our study provides new gene markers for predicting replicative senescence and the available quantity of MPCs but may also help to guide the development of new standard criteria for manufacturing.
间充质祖细胞(MPCs)因其免疫调节特性、抗炎分子分泌以及受损细胞的替代作用,是再生医学有前途的细胞来源。尽管具有这些优势,但 MPC 功能潜力的异质性和有限的增殖能力,以及缺乏合适的产品效力标志物,阻碍了 MPC 大规模制造工艺的发展。因此,需要在体外持续开发具有高增殖能力和标准化的 MPC,并寻找合适的功能标志物来衡量产品效力。在这项研究中,使用增殖测定和微阵列,建立了三条具有高增殖能力的多能干细胞(PSC)衍生 MPC 系,并与骨髓衍生 MPC 进行了比较。在增殖能力最高的 MPC 系(CHA-hNT5-MPCs)中,有 6 个基因显著过表达(>10 倍),并通过 qRT-PCR 进行了验证。然而,只有两个基因(MYOCD 和 ODZ2)在体外与 MPC 衰老具有显著相关性。我们的研究为预测 MPC 复制衰老和可用数量提供了新的基因标志物,但也可能有助于指导制造新的标准标准的制定。