3 years ago

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

Survivin is Required for Mouse and Human Bone Marrow Mesenchymal Stromal Cell Function
Seiji Fukuda, Pratibha Singh, Brahmananda Reddy Chitteti, Louis M. Pelus, Liqiong Liu
Although mesenchymal stromal cells (MSC) 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 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 (b-FGF) and platelet derived growth factor (PDGF). 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. This article is protected by copyright. All rights reserved. Pharmacological or genetic blockade of Survivin expression in mouse and human bone marrow MSC enhances apoptosis and reduces proliferation, CFU-F formation, migration and hematopoietic niche activity, whereas Survivin over expression via growth factors/genetic modulation in MSC results in their expansion and enhancement of hematopoietic regeneration after irradiation injury.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/stem.2727

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