Replicative Senescence Markers in Serially Passaged Human Mesenchymal Stromal Cells
DOI:
https://doi.org/10.5281/zenodo.22274369Keywords:
Mesenchymal stromal cells; Replicative senescence; Serial passage; Methylation drift; Cell therapy manufacturingAbstract

Background: Every therapeutic mesenchymal stromal cell lot is expanded for weeks, but the identity criteria used to release
it say nothing about how many divisions it has already spent.
Objective: To examine what serial-passage studies have measured, and which readouts could serve as release specifications
or potency inputs.
Methods: Narrative review of serial-passage cohorts, telomere and methylation studies, and functional assays.
Findings: Expansion capacity spans roughly 8 to 86 cumulative population doublings across published cohorts.
Senescence-associated beta-galactosidase-positive cells rose from 4.23 +/- 1.6% at passage 2 to 90.48 +/- 3.29% at passage 20
in five adipose preparations, and telomere length fell from 9.19 to 8.7 kbp between passages 1 and 9.
Conclusions: The evidence supports a continuous measure of expansion history paired with a mechanism-matched potency
assay, but not passage number as a release criterion, nor claims that expansion causes transformation.
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