Aging and cell expansion enhance microRNA diversity in small extracellular vesicles produced from human adipose-derived stem cells

被引：1

作者：

Tsubaki, Toshiya ^{[1
]}

Chijimatsu, Ryota ^{[1
,4
]}

Takeda, Taiga ^{[6
]}

Abe, Maki ^{[5
]}

Ochiya, Takahiro ^{[5
]}

Tsuji, Shinsaku ^{[6
]}

Inoue, Keita ^{[6
]}

Matsuzaki, Tokio ^{[6
]}

Iwanaga, Yasuhide ^{[1
,3
]}

Omata, Yasunori ^{[1
,2
]}

Tanaka, Sakae ^{[1
]}

Saito, Taku ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Orthopaed Surg Sensory & Motor Syst Med, 7-3-1 Hongo,Bunkyo Ku, Tokyo 1138655, Japan

[2] Univ Tokyo Hosp, Bone & Cartilage Regenerat Med, 7-3-1 Hongo,Bunkyo Ku, Tokyo 1138655, Japan

[3] Univ Tokyo, Dept Chem & Biotechnol, Grad Sch Engn, 7-3-1 Hongo,Bunkyo Ku, Tokyo 1138656, Japan

[4] Okayama Univ Hosp, Ctr Comprehens Genom Med, 2-5-1 Shikada Chou,Kita Ku, Okayama 7008558, Japan

[5] Tokyo Med Univ, Dept Mol & Cellular Med, 6-7-1 Nishishinjuku,Shinjuku Ku, Tokyo 1600023, Japan

[6] CPC Corp, 3-4 Kanda Surugadai,Chiyoda ku, Tokyo 1010062, Japan

来源：

CYTOTECHNOLOGY | 2025年 / 77卷 / 01期

基金：

日本科学技术振兴机构;

关键词：

Adipose-derived stem cells; Extracellular vesicles; microRNA; Regenerative therapy; GENE-EXPRESSION; STROMAL CELLS; EXOSOMES; DISEASE; PROLIFERATION; SENESCENCE; MIGRATION; THERAPY;

D O I：

10.1007/s10616-024-00675-6

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Adipose-derived stem cells (ASCs) and their small extracellular vesicles (sEVs) hold significant potential for regenerative medicine due to their tissue repair capabilities. The microRNA (miRNA) content in sEVs varies depending on ASC status; however, the effects of aging and cell passage on miRNA profiles remain unclear. In this study, we examined the effects of donor age and cell expansion on ASC characteristics and transcriptome using ASCs obtained from three young and three old donors. Cell expansion significantly impaired stem cell properties, notably reducing proliferation and differentiation capacities. In contrast, donor age had minimal effects on ASCs. RNA sequencing (RNA-seq) revealed differences in gene expression related to stemness, phagocytosis, and metabolic processes influenced by cell expansion. To investigate miRNA variability, we performed small RNA-seq on sEVs collected from ASCs of all six donors. The miRNA profiles were influenced by donor age and cell passage. Interestingly, functional enrichment analysis indicated that advanced donor age and increased cell passage may enhance the production of miRNAs associated with organ development through various pathways. These findings suggest that donor age and cell expansion differentially influence ASC characteristics and sEV miRNA content, highlighting the need for disease-specific conditioning of ASCs to optimize the therapeutic effects of sEVs in clinical applications.

引用

页数：18