Bone marrow-derived mesenchymal stem cells (MSCs) offer promise as a cell therapy for heart repair and wound healing. Low survival and poor engraftment of MSCs limit their therapeutic potential, so researchers are attempting to identify strategies that enhance MSC survival and proliferation, and maintain their “stemness” (inhibit their differentiation into more mature cell types).
Pampee Young, associate professor of pathology, microbiology and immunology, research fellow Sarika Saraswati and colleagues previously showed that inhibition of Wnt signaling – with an over-expressed protein inhibitor – increased the proliferation and engraftment of MSCs in mice. Now, the investigators report that pyrvinium, a small molecule inhibitor of Wnt signaling, increases MSC proliferation and inhibits MSC differentiation in vitro. In an in vivo wound repair model in mice, they demonstrate that pyrvinium enhances long-term MSC engraftment and prevents ectopic differentiation of the tissue into bone or cartilage.
The study, in the March-April issue of Wound Repair and Regeneration, highlights the potential of using a small molecule Wnt inhibitor to enhance stem cell survival and improve cell-based therapies for regenerative medicine.
This research was supported by National Institutes of Health grants from the National Heart, Lung and Blood Institute and the National Institute of General Medical Sciences, and by a Veterans Affairs merit award.