Stem Cell Institute, ENCell Co. Ltd., Seoul 06072, Korea.
Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul 06351, Korea.
Int J Mol Sci. 2020 Sep 25;21(19):7092. doi: 10.3390/ijms21197092.
Mesenchymal stem cells (MSCs) are safe, and they have good therapeutic efficacy through their paracrine action. However, long-term culture to produce sufficient MSCs for clinical use can result in side-effects, such as an inevitable senescence and the reduction of the therapeutic efficacy of the MSCs. In order to overcome this, the primary culture conditions of the MSCs can be modified to simulate the stem cells' niche environment, resulting in accelerated proliferation, the achievement of the target production yield at earlier passages, and the improvement of the therapeutic efficacy. We exposed Wharton's jelly-derived MSCs (WJ-MSCs) to pressure stimuli during the primary culture step. In order to evaluate the proliferation, stemness, and therapeutic efficacy of WJ-MSCs, image, genetic, and Western blot analyses were carried out. Compared with standard incubation culture conditions, the cell proliferation was significantly improved when the WJ-MSCs were exposed to pressure stimuli. However, the therapeutic efficacy (the promotion of cell proliferation and anti-apoptotic effects) and the stemness of the WJ-MSCs was maintained, regardless of the culture conditions. Exposure to pressure stimuli is a simple and efficient way to improve WJ-MSC proliferation without causing changes in stemness and therapeutic efficacy. In this way, clinical-grade WJ-MSCs can be produced rapidly and used for therapeutic applications.
间充质干细胞(MSCs)是安全的,它们通过旁分泌作用具有良好的治疗效果。然而,为了临床应用而进行长期培养以产生足够数量的 MSCs 可能会导致副作用,例如不可避免的衰老和 MSC 治疗效果的降低。为了克服这一点,可以修改 MSC 的原代培养条件,以模拟干细胞的生态位环境,从而加速增殖,在更早的传代中实现目标产物产量,并提高治疗效果。我们在原代培养步骤中对牙髓来源的间充质干细胞(WJ-MSCs)施加压力刺激。为了评估 WJ-MSCs 的增殖、干性和治疗效果,进行了图像、遗传和 Western blot 分析。与标准孵育培养条件相比,当 WJ-MSCs 受到压力刺激时,细胞增殖显著提高。然而,无论培养条件如何,WJ-MSCs 的治疗效果(促进细胞增殖和抗凋亡作用)和干性都得到了维持。暴露于压力刺激是一种简单有效的提高 WJ-MSC 增殖的方法,而不会导致干性和治疗效果发生变化。通过这种方式,可以快速生产临床级别的 WJ-MSCs 并用于治疗应用。