Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam-si 13494, Korea.
Cells. 2021 Sep 14;10(9):2420. doi: 10.3390/cells10092420.
Mesenchymal stem cells (MSCs) are accessible, abundantly available, and capable of regenerating; they have the potential to be developed as therapeutic agents for diseases. However, concerns remain in their further application. In this study, we developed a SMall cell+Ultra Potent+Scale UP cell (SMUP-Cell) platform to improve whole-cell processing, including manufacturing bioreactors and xeno-free solutions for commercialization. To confirm the superiority of SMUP-Cell improvements, we demonstrated that a molecule secreted by SMUP-Cells is capable of polarizing inflammatory macrophages (M1) into their anti-inflammatory phenotype (M2) at the site of injury in a pain-associated osteoarthritis (OA) model. Lipopolysaccharide-stimulated macrophages co-cultured with SMUP-Cells expressed low levels of M1-phenotype markers (CD11b, tumor necrosis factor-α, interleukin-1α, and interleukin-6), but high levels of M2 markers (CD163 and arginase-1). To identify the paracrine action underlying the anti-inflammatory effect of SMUP-Cells, we employed a cytokine array and detected increased levels of pentraxin-related protein-3 (PTX-3). Additionally, mRNA silencing was applied to confirm PTX-3 function. silencing in SMUP-Cells significantly decreased their therapeutic effects against monosodium iodoacetate (MIA)-induced OA. Thus, PTX-3 expression in injected SMUP-Cells, applied as a therapeutic strategy, reduced pain in an OA model.
间充质干细胞（MSCs）易于获取、丰富且具有再生能力；它们有可能被开发为治疗疾病的治疗剂。然而，在进一步应用方面仍存在一些问题。在这项研究中，我们开发了一种小型细胞+超高效+大规模细胞（SMUP-Cell）平台，以改善整个细胞处理过程，包括制造生物反应器和无动物源解决方案以实现商业化。为了证实 SMUP-Cell 改进的优越性，我们证明了 SMUP-Cells 分泌的一种分子能够将炎症性巨噬细胞（M1）在疼痛相关骨关节炎（OA）模型中受伤部位极化为抗炎表型（M2）。与 SMUP-Cells 共培养的脂多糖刺激的巨噬细胞表达低水平的 M1 表型标志物（CD11b、肿瘤坏死因子-α、白细胞介素-1α和白细胞介素-6），但高水平的 M2 标志物（CD163 和精氨酸酶-1）。为了确定 SMUP-Cells 抗炎作用的旁分泌作用，我们采用细胞因子阵列检测到 pentraxin-related protein-3 (PTX-3) 水平升高。此外，还应用 mRNA 沉默来确认 PTX-3 的功能。在 SMUP-Cells 中沉默 PTX-3 显著降低了它们对单碘乙酸盐（MIA）诱导的 OA 的治疗效果。因此，注射的 SMUP-Cells 中 PTX-3 的表达作为一种治疗策略，减轻了 OA 模型中的疼痛。
