Senescence recovering by dual drug-encapsulated liposomal nanoparticles for large-scale human cell expansion
Senescence recovering by dual drug-encapsulated liposomal nanoparticles for large-scale human cell expansion
复制标题
通过双重药物封装的脂质体纳米颗粒恢复衰老，用于大规模人体细胞扩增
DOI：
10.1007/s10047-022-01356-x
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发表时间：
2022
影响因子：
1.3
通讯作者：
Hiroyoshi Kawakami
中科院分区：
文献类型：
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作者：
Keisuke Ashiba;Koki Mino;Yui Okido;Kiyoshi Sato;Hiroyoshi Kawakami
尽管再生治疗和生物人工组织和器官需要足够数量的人细胞，但目前的细胞扩增过程伴随着衰老细胞的积累，这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，在扩张过程中抑制复制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（LNP），以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-MSC）和自然杀伤（NK）细胞中的细胞衰老。我们发现LNP处理减少了衰老标记物;两种细胞中p21表达的下调和SA-β-Gal活性的降低可证明是由于细胞中的线粒体自噬再激活。此外，在LNP处理后，hAT-MSC中的SASP分泌和NK细胞中的肿瘤细胞毒性也得到改善。这些发现可能有助于生产用于再生医学和生物人工组织和器官的高效扩增细胞。
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.