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

Area of Science:

• Stem cell biology
• Developmental biology
• Bone biology

Background:

• Mesenchymal stem cells (MSCs) are crucial for cell therapy and regenerative medicine.
• Their developmental origins and in vivo identity remain largely uncharacterized.
• Fibroblast growth factors (FGFs) are vital for bone development, with developmentally regulated receptors.

Purpose of the Study:

• To investigate the expression and role of fibroblast growth factor receptors (FGFRs) in bone-derived MSCs.
• To understand the developmental regulation and in vivo identity of MSCs.
• To explore FGFRs' potential involvement in maintaining MSC stemness.

Main Methods:

• In vivo analysis of FGFR1/2 expression in murine bone marrow and skeletal tissues.
• Isolation and in vitro expansion of mesenchymal progenitors.
• Assessment of MSC phenotype, proliferation, and senescence following FGF-2 treatment.

Main Results:

• FGFR1 and FGFR2 were detected in rare mesenchymal progenitors within MSC niches (perichondrium, periosteum, trabecular marrow).
• FGFR1-expressing cells were often identified as pericytes.
• FGF-2 treatment maintained MSC stemness in vitro by promoting proliferation and inhibiting senescence via the PI3K/AKT-MDM2 pathway.

Conclusions:

• FGFR1/2 serve as developmentally regulated markers for MSCs in vivo and in vitro.
• FGFR signaling is critical for maintaining MSC stemness and self-renewal.
• These findings provide insights into MSC developmental biology and potential therapeutic applications.