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Directed Differentiation of Primitive and Definitive Hematopoietic Progenitors from Human Pluripotent Stem Cells
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WNT and VEGF/PDGF signaling regulate self-renewal in primitive mesenchymal stem cells

Matteo Mazzella1, Keegan Walker1, Christina Cormier1

  • 1Oakland University.

Research Square
|April 24, 2023
PubMed
Abstract

Insights

Mesenchymal stem cell (MSC) self-renewal is crucial for therapy but declines with propagation. Xeno-free medium preserves MSC self-renewal and differentiation potential by modulating key signaling pathways, unlike traditional serum media.

Area of Science:

  • Stem Cell Biology
  • Regenerative Medicine

Background:

  • Therapeutic applications of multipotent mesenchymal stem cells (MSCs) are limited by poor growth and reduced self-renewal capacity during propagation.
  • Understanding the molecular mechanisms governing MSC self-renewal is critical for improving cell-based therapies.

Approach:

  • Primitive MSCs (pMSCs) were cultured in fetal bovine serum medium (FM) and xeno-free medium (XM) to low (P3) and high (P20) passages.
  • Comprehensive characterization included morphology, cell surface marker expression, proliferation assays, telomerase activity, and trilineage differentiation.
  • Transcriptome (RNA-seq) and nucleosome occupancy (MNase-seq) analyses were performed to investigate molecular changes.

Key Points:

  • pMSCs in FM exhibited reduced self-renewal markers (CD90, CD49f), colony-forming efficiency, proliferation, and telomerase activity, with increased adipogenic differentiation.
  • pMSCs in XM maintained fibroblastoid morphology, self-renewal capacity, and differentiation potential.
  • XM-cultured pMSCs showed upregulated self-renewal and cell cycle genes, while FM-cultured cells displayed upregulated senescence genes. Nucleosome occupancy patterns correlated with these gene expression changes.

Conclusions:

  • Xeno-free medium supports the long-term self-renewal and differentiation potential of primitive MSCs.
  • WNT and VEGF/PDGF signaling pathways are implicated in maintaining MSC self-renewal.
  • TGFβ and PI3K signaling pathways appear to induce senescence in MSCs.
Keywords:
Mesenchymal stem cellsPDGFTGFβVEGFWNTdifferentiationproliferationself-renewalsenescencesignaling pathway

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