Aging of mesenchymal stem cell in vitro

TLDR

Mesenchymal stem cells (MSC) are a promising therapeutic modality, but their low bone marrow frequency requires in‑vitro expansion for clinical use. The study cultured MSCs for an average of 118 days, reaching passage 9, to assess senescence. Long‑term culture caused marked senescence: population doublings fell from 7.7 to 1.2, telomeres shortened, differentiation potential declined after passage 6, and morphological changes consistent with Hayflick aging appeared, indicating MSCs lose stemness early and should be used promptly.

Abstract

A hot new topic in medical treatment is the use of mesenchymal stem cells (MSC) in therapy. The low frequency of this subpopulation of stem cells in bone marrow (BM) necessitates their in vitro expansion prior to clinical use. We evaluated the effect of long term culture on the senescence of these cells.The mean long term culture was 118 days and the mean passage number was 9. The average number of PD decreased from 7.7 to 1.2 in the 10th passage. The mean telomere length decreased from 9.19 Kbp to 8.7 kbp in the 9th passage. Differentiation potential dropped from the 6th passage on. The culture's morphological abnormalities were typical of the Hayflick model of cellular aging.We believe that MSC enter senescence almost undetectably from the moment of in vitro culturing. Simultaneously these cells are losing their stem cell characteristics. Therefore, it is much better to consider them for cell and gene therapy early on.