E-viri
Recenzirano
Odprti dostop
-
Psaroudis, Rose Triantafillia; Singh, Urvashi; Lora, Maximilien; Jeon, Peter; Boursiquot, Abigail; Stochaj, Ursula; Langlais, David; Colmegna, Inés
Stem cell research & therapy, 07/2022, Letnik: 13, Številka: 1Journal Article
Introduction Human mesenchymal stromal cells (MSCs) have immunomodulatory, anti-inflammatory, and tolerogenic effects. Long-term in vitro expansion of MSCs to generate clinical grade products results in the accumulation of senescent-functionally impaired MSCs. Markers to assess the 'senescent load' of MSC products are needed. Methods Early and late passage human adipose tissue (AT) MSCs from pediatric and adult donors were characterized using established senescent markers i.e., MSC size, granularity, and autofluorescence by flow cytometry; beta-galactosidase staining (SA-beta-gal); CDKN2A and CDKN1A by qRT-PCR. In gene set enrichment analysis, DPP4 (also known as adenosine deaminase complexing protein 2 or CD26) was found as a prominent dysregulated transcript that was increased in late passage MSC(AT). This was confirmed in a larger number of MSC samples by PCR, flow cytometry, Western blotting, and immunofluorescence. In vitro immunopotency assays compared the function of CD26.sup.high and CD26.sup.low MSC(AT). The effect of senolytics on the CD26.sup.high subpopulation was evaluated in senescent MSC(AT). Results Late passage MSC(AT) had a senescence transcriptome signature. DPP4 was the most differentially enriched gene in senescent MSCs. Late passage senescent MSC(AT) had higher CD26 surface levels and total protein abundance. Moreover, CD26 surface levels were higher in early passage MSC(AT) from adults compared to pediatric donors. CD26 abundance correlated with established senescence markers. CD26.sup.high MSC(AT) had reduced immunopotency compared to CD26.sup.low MSC(AT). Senolytic treatment induced MSC apoptosis, which decreased the frequencies of CD26.sup.high MSC(AT). Conclusions DPP4 gene expression and DPP4/CD26 protein abundance are markers of replicative senescence in MSC(AT). Samples enriched in CD26.sup.high MSC(AT) have reduced immunopotency and CD26.sup.high MSCs are reduced with senolytics. Keywords: Mesenchymal stromal cells (MSCs), Adipose tissue (AT), CD26, Dipeptidyl peptidase 4 (DPP4), Senescence, Aging
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.