Restricted accessResearch articleFirst published online 2025-11
Strong Transcriptional Signature of Mesenchymal Stromal Cells from Perinatal Tissues Compared with Adult Bone Marrow Sources Independent of Donors or Culture Conditions
Mesenchymal stromal cells (MSCs) are currently used in clinical practice as a therapeutic agent for immunomodulation and tissue repair. They are found in all supporting tissues, including perinatal tissues such as umbilical cord and amniotic membranes (amnion and chorion). Perinatal tissues have attracted interest due to their availability, minimal ethical and legal concerns, and high banking potential for allogeneic applications. Many studies have compared the efficacy of MSCs from different sources, without reaching a consensus on the most effective to use in a given clinical situation. This study compared the transcriptomic signatures of MSCs derived from adult bone marrow (BM-MSCs)—the reference source most widely used in clinical trials—with those of perinatal MSCs (P-MSCs). Our data were analyzed jointly with three independent transcriptome datasets. Unsupervised principal component analysis revealed a major stratification according to tissue origin, accounting for 16.6% of the total transcriptomic variance, without any detectable bias from batch effects or cell culture procedures. Supervised differential expressed gene analysis between BM and perinatal samples revealed 819 genes presenting differential expression. Gene Set Enrichment Analysis highlighted that adult BM-MSCs are implicated in adipogenesis and osteoblast differentiation, whereas P-MSCs upregulated gene sets implicated in cell cycle regulation, functions classically described in the literature. Among the different sources of variability, we showed that perinatal tissues have a strongly distinct transcriptional signature compared with adult BM, independent of the production center or the culture conditions used. The in-depth study of transcript profiles therefore seems to remain a valuable and robust characterization tool for cell therapy banking.
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