Podoplanin depletion in tonsil-derived mesenchymal stem cells induces cellular senescence via regulation of the p16Ink4a/Rb pathway.
Cell Commun Signal
; 22(1): 323, 2024 Jun 12.
Article
en En
| MEDLINE
| ID: mdl-38867259
ABSTRACT
BACKGROUND:
Mesenchymal stem cells (MSCs) are widely used in the development of therapeutic tools in regenerative medicine. However, their quality decreases during in vitro expansion because of heterogeneity and acquired cellular senescence. We investigated the potential role of podoplanin (PDPN) in minimizing cellular senescence and maintaining the stemness of tonsil-derived MSCs (TMSCs).METHODS:
TMSCs were isolated from human tonsil tissues using an enzymatic method, expanded, and divided into two groups early-passaged TMSCs, which were cultured for 3-7 passages, and late-passaged TMSCs, which were passaged more than 15 times. The TMSCs were evaluated for cellular senescence and MSC characteristics, and PDPN-positive and -negative cells were identified by fluorescence-activated cell sorting. In addition, MSC features were assessed in siRNA-mediated PDPN-depleted TMSCs.RESULTS:
TMSCs, when passaged more than 15 times and becoming senescent, exhibited reduced proliferative rates, telomere length, pluripotency marker (NANOG, OCT4, and SOX2) expression, and tri-lineage differentiation potential (adipogenesis, chondrogenesis, or osteogenesis) compared to cells passaged less than five times. Furthermore, PDPN protein levels significantly decreased in a passage-dependent manner. PDPN-positive cells maintained their stemness characteristics, such as MSC-specific surface antigen (CD14, CD34, CD45, CD73, CD90, and CD105) and pluripotency marker expression, and exhibited higher tri-lineage differentiation potential than PDPN-negative cells. SiRNA-mediated silencing of PDPN led to decreased cell-cycle progression, proliferation, and migration, indicating the significance of PDPN as a preliminary senescence-related factor. These reductions directly contributed to the induction of cellular senescence via p16Ink4a/Rb pathway activation.CONCLUSION:
PDPN may serve as a novel biomarker to mitigate cellular senescence in the clinical application of MSCs.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tonsila Palatina
/
Glicoproteínas de Membrana
/
Senescencia Celular
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Inhibidor p16 de la Quinasa Dependiente de Ciclina
/
Células Madre Mesenquimatosas
Límite:
Humans
Idioma:
En
Revista:
Cell Commun Signal
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Reino Unido