Department of Applied Chemistry for Environment, Graduate School of Urban Environmental Sciences, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo, 192-0397, Japan.
J Artif Organs. 2023 Sep;26(3):246-250. doi: 10.1007/s10047-022-01356-x. Epub 2022 Aug 19.
Although regenerative therapy and bioartificial tissues and organs require a sufficient number of human cells, current cell expansion processes are accompanied by accumulation of senescent cells that are related to deterioration of cellular functions and induction of senescence-associated secretory phenotype (SASP). Therefore, suppression of replicative senescence during expansion is one of the crucial issues for dissemination of regenerative medicine. We herein developed dual drug-encapsulated liposomal nanoparticles (LNPs) to suppress cellular senescence in human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) and natural killer (NK) cells by removal of dysfunctional mitochondria from the senescent cells. We found that LNP treatment reduced senescent makers; downregulation of p21 expression and reduction of SA-β-Gal activity in both cells provably due to mitophagy reactivation in the cells. Moreover, SASP secretion in hAT-MSCs and tumor cytotoxicity in NK cells were also improved upon LNP treatments. These findings may contribute to the production of highly effective expanded cells for regenerative medicine and bioartificial tissues and organs.
尽管再生疗法和生物人工组织和器官需要足够数量的人类细胞，但目前的细胞扩增过程伴随着衰老细胞的积累，这些细胞与细胞功能的恶化和衰老相关分泌表型（SASP）的诱导有关。因此，在扩增过程中抑制复制性衰老是再生医学传播的关键问题之一。我们在此开发了双重药物包封的脂质体纳米颗粒（LNPs），通过从衰老细胞中去除功能失调的线粒体来抑制人脂肪组织来源的间充质干细胞（hAT-MSCs）和自然杀伤（NK）细胞中的细胞衰老。我们发现 LNP 处理降低了衰老标志物；p21 表达下调和 SA-β-Gal 活性降低，这两种细胞中的细胞因细胞自噬的重新激活而减少。此外，LNPs 处理还改善了 hAT-MSCs 的 SASP 分泌和 NK 细胞的肿瘤细胞毒性。这些发现可能有助于为再生医学和生物人工组织和器官生产高效扩增的细胞。
