WNT and VEGF/PDGF signaling regulate self-renewal in primitive mesenchymal stem cells

Therapeutic use of mesenchymal stem cells (MSCs) is hampered due to poor growth and self-renewal potential. They are also affected by passaging. This study found that xeno-free medium (XM) maintained morphology, self-renewal, and differentiation potential in primitive (p) MSCs. In contrast, growth in fetal bovine serum medium (FM) resulted in gradual changes in morphology, differentiation capability and reduced colony-forming efficiency. Transcriptomic analysis showed upregulation of genes involved in self-renewal, cell cycle, and DNA replication in XM-grown pMSCs. However, differentiation and senescence genes were upregulated in FM-grown cells. The expression of selected genes was corroborated by qRT-PCR analyses. We also examined changes in chromatin structure by MNase-seq. We proposed WNT and VEGF/PDGF signaling pathways are involved in self-renewal and TGFB, and PI3K signaling pathways are responsible for the induction of senescence in pMSCs. Our findings may help expand pMSCs for large-scale preclinical and clinical studies, which have been limited thus far.