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Senescence recovering by dual drug-encapsulated liposomal nanoparticles for large-scale human cell expansion

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  • Tissue Engineering / Regenerative Medicine
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Abstract

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.

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Acknowledgements

The authors would like to thank the Biotherapy Institute of Japan for providing primary hAT-MSCs.

Funding

This work was partially supported by JSPS KAKENHI (Grant Number JP21K19920).

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Authors and Affiliations

  1. Department of Applied Chemistry for Environment, Graduate School of Urban Environmental Sciences, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo, 192-0397, Japan

    Keisuke Ashiba, Koki Mino, Yui Okido, Kiyoshi Sato & Hiroyoshi Kawakami

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  1. Keisuke Ashiba
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  2. Koki Mino
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  3. Yui Okido
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  4. Kiyoshi Sato
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  5. Hiroyoshi Kawakami
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Correspondence to Hiroyoshi Kawakami.

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Ashiba, K., Mino, K., Okido, Y. et al. Senescence recovering by dual drug-encapsulated liposomal nanoparticles for large-scale human cell expansion. J Artif Organs 26, 246–250 (2023). https://doi.org/10.1007/s10047-022-01356-x

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  • DOI: https://doi.org/10.1007/s10047-022-01356-x

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