Blood Journal
Leading the way in experimental and clinical research in hematology

Inhibition of cellular senescence by developmentally regulated FGF receptors in mesenchymal stem cells

  1. Daniel L. Coutu1,2,*,
  2. Moïra François1,2,*, and
  3. Jacques Galipeau14
  1. 1Division of Experimental Medicine, McGill University, Montreal, QC;
  2. 2Sir Mortimer B. Davis Jewish General Hospital and Lady Davis Institute for Medical Research, Montreal, QC; and
  3. Departments of 3Hematology and Medical Oncology and
  4. 4Pediatrics, Emory University, Winship Cancer Institute, Atlanta, GA

Abstract

Bone-derived mesenchymal stem cells (MSCs) are important cells for use in cell therapy, tissue engineering, and regenerative medicine, but also to study bone development, homeostasis, and repair. However, little is known about their developmental ontology and in vivo identity. Because fibroblast growth factors (FGFs) play key roles in bone development and their receptors are developmentally regulated in bones, we hypothesized that MSCs should express FGF receptors (FGFRs), reflecting their developmental origin and potential. We show here that FGFR1/2 are expressed by rare mesenchymal progenitors in putative MSC niches in vivo, including the perichondrium, periosteum, and trabecular marrow. FGFR1+ cells often appeared as pericytes. These cells display a characteristic MSC phenotype in vitro when expanded with FGF-2, which appears to maintain MSC stemness by inhibiting cellular senescence through a PI3K/AKT-MDM2 pathway and by promoting proliferation. FGFRs may therefore be involved in MSC self-renewal. In summary, FGFR1/2 are developmentally regulated markers of MSCs in vivo and in vitro and are important in maintaining MSC stemness.

  • Submitted December 3, 2010.
  • Accepted April 18, 2011.
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