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Promoting Mesenchymal Stem Cell Function with Survivin

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Review of “Survivin Is Required for Mouse and Human Bone Marrow Mesenchymal Stromal Cell Function” from STEM CELLS by Stuart P. Atkinson

Delineating the pathways that control mesenchymal stromal cell (MSC) may allow the construction of more efficient cell-based therapeutics for a wide-range of diseases and disorders. To this end, researchers from the laboratories of Louis M. Pelus and Pratibha Singh (Indiana University School of Medicine, USA) have been studying the function of an endogenous inhibitor-of-apoptosis protein family member (Survivin) in human and mouse MSCs [1, 2]. Perhaps unsurprisingly (!), their new STEM CELLS brief report establishes that Survivin regulates survival in MSCs, but the authors also demonstrate a role in proliferation, differentiation, and migration [3].

This study employed pharmacological or genetic inhibition of Survivin in both human and mouse bone marrow-derived MSCs and discovered:

  • Reduced human and mouse MSC proliferation and survival and increased levels of apoptosis (enhanced caspase 3 and 7 expression)
  • Diminished response of MSCs to proliferative factors (basic fibroblast growth factor [bFGF] and platelet-derived growth factor [PDGF])
  • Alterations to the tri-potential differentiation capabilities of MSCs
    • Mouse MSCs displayed decreased differentiation into adipocytes and chondrocytes and enhanced differentiation into osteoblasts
    • However, human MSCs exhibited reduced differentiation into all three lineages 
  • Reduced cell migration into a wound site in an ex vivo scratch assay
    • Migrational inhibition resulted from cytoskeletal modulation
  • Irradiation of model mice also led to reduced Survivin expression in MSCs, the number of bone marrow MSCs, and MSC’s ability to support hematopoiesis in a co-culture assay
    • However, increasing levels of Survivin via bFGF treatment partially protected against the loss of MSCs.

The authors hope that these findings may foster Survivin modulation as an efficient strategy to enhance MSC function and, in particular, provide enhanced support for hematopoietic regeneration following irradiation exposure.

For more on new strategies to enhance the therapeutic application of MSCs, stay tuned to the Stem Cells Portal!

References

  1. Ambrosini G, Adida C, and Altieri DC, A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 1997;3:917-21.
  2. Adida C, Crotty PL, McGrath J, et al., Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation. Am J Pathol 1998;152:43-9.
  3. Singh P, Fukuda S, Liu L, et al., Survivin Is Required for Mouse and Human Bone Marrow Mesenchymal Stromal Cell Function. STEM CELLS 2018;36:123-129.