Survivin Is Required for Mouse and Human Bone Marrow Mesenchymal Stromal Cell Function

Pratibha Singh, Seiji Fukuda, Liqiong Liu, Brahmananda Reddy Chitteti, Louis M. Pelus

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Although mesenchymal stromal cells (MSCs) have significant potential in cell-based therapies, little is known about the factors that regulate their functions. While exploring regulatory molecules potentially involved in MSC activities, we found that the endogenous multifunctional factor Survivin is essential for MSC survival, expansion, lineage commitment, and migration. Pharmacological or genetic blockade of Survivin expression in mouse and human bone marrow MSC enhances caspase 3 and 7 expression and reduces proliferation resulting in fewer MSC and clonogenic colony-forming unit-fibroblasts (CFU-F), whereas ectopic Survivin overexpression in MSC results in their expansion. Survivin is also required for the MSC proliferative responses to basic fibroblast growth factor and platelet derived growth factor. In a wound healing model, Survivin inhibition results in suppression of MSC migration to the wound site. In addition, loss of Survivin in MSCs compromises their hematopoiesis-supporting capacity. These results demonstrate that Survivin is a key regulator of mouse and human MSC function, and suggest that targeted modulation of Survivin in MSCs may have clinical utility to enhance MSC recovery and activity following insult or stress. Stem Cells 2018;36:123–129.

Original languageEnglish (US)
Pages (from-to)123-129
Number of pages7
JournalSTEM CELLS
Volume36
Issue number1
DOIs
StatePublished - Jan 2018

Keywords

  • Adult hematopoietic stem cells
  • Adult stem cells
  • Bone marrow stromal cells
  • Cellular proliferation
  • Flow cytometry
  • Mesenchymal stem cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Singh, P., Fukuda, S., Liu, L., Chitteti, B. R., & Pelus, L. M. (2018). Survivin Is Required for Mouse and Human Bone Marrow Mesenchymal Stromal Cell Function. STEM CELLS, 36(1), 123-129. https://doi.org/10.1002/stem.2727