{"title":"Aging and cell expansion enhance microRNA diversity in small extracellular vesicles produced from human adipose-derived stem cells.","authors":"Toshiya Tsubaki, Ryota Chijimatsu, Taiga Takeda, Maki Abe, Takahiro Ochiya, Shinsaku Tsuji, Keita Inoue, Tokio Matsuzaki, Yasuhide Iwanaga, Yasunori Omata, Sakae Tanaka, Taku Saito","doi":"10.1007/s10616-024-00675-6","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s10616-024-00675-6.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"77 1","pages":"15"},"PeriodicalIF":2.0000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631832/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cytotechnology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s10616-024-00675-6","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/10 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
Supplementary information: The online version contains supplementary material available at 10.1007/s10616-024-00675-6.
期刊介绍:
The scope of the Journal includes:
1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products.
2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools.
3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research.
4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy.
5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.