[P005] Poster

12:10 PM - 1:00 PM JST(3:10 AM - 4:00 AM UTC)

[P03-421] REJUVANATION OF SENESCENT MESENCHYMAL STEM/STROMAL CELLS BY MITOPHAGY REACTIVATION

○Kiyoshi Sato¹, Sogo Aoki¹, Hiroyoshi Kawakami¹ (1. Tokyo Metropolitan University (Japan))

Keywords:

Mesenchymal stem/stromal cell,Cellular senescence,Mitophagy

Regenerative therapy and bioartificial tissues/organs require a large quantity of human cells. However, current cell manufacturing processes are accompanied by cellular senescence, leading to the deterioration of cell proliferation and function together with the secretion of senescence-associated secretory phenotype (SASP) factors. Therefore, suppression of replicative senescence during expansion/production culture is one of the crucial issues for the development of regenerative medicine. We herein report dual drug-encapsulated liposomal nanoparticles to suppress cellular senescence in human adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs), a promising cell source for regenerative medicine and stem cell-based therapy, by removal of dysfunctional mitochondria from cultured AT-MSCs. We found that the nanoparticle treatment induces mitophagy, recovers cell proliferation ability, and reduces senescent makers in the cells via mitophagy reactivation. SASP secretion from the cells also improved by the treatment. Our findings may contribute to the production and availability of MSCs suitable for medical applications and tissue engineering. This work was supported by the Tokyo Metropolitan Government Infectious Disease Research Project and Advanced Research (Grant Number R4-1), TMU GAP Fund, and by JSPS KAKENHI (Grant Number JP23H03743).