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Agonism of Wnt–β‐catenin signalling promotes mesenchymal stem cell (MSC) expansion
Authors:Michael D Hoffman  Danielle SW Benoit
Institution:Departments of Biomedical Engineering, Chemical Engineering and Orthopaedics and Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA
Abstract:Promoting mesenchymal stem cell (MSC) proliferation has numerous applications in stem cell therapies, particularly in the area of regenerative medicine. In order for cell‐based regenerative approaches to be realized, MSC proliferation must be achieved in a controlled manner without compromising stem cell differentiation capacities. Here we demonstrate that 6‐bromoindirubin‐3′‐oxime (BIO) increases MSC β‐catenin activity 106‐fold and stem cell‐associated gene expression ~33‐fold, respectively, over untreated controls. Subsequently, BIO treatment increases MSC populations 1.8‐fold in typical 2D culture conditions, as well as 1.3‐fold when encapsulated within hydrogels compared to untreated cells. Furthermore, we demonstrate that BIO treatment does not reduce MSC multipotency where MSCs maintain their ability to differentiate into osteoblasts, chondrocytes and adipocytes using standard conditions. Taken together, our results demonstrate BIO's potential utility as a proliferative agent for cell transplantation and tissue regeneration. Copyright © 2013 John Wiley & Sons, Ltd.
Keywords:mesenchymal stem cells  hydrogel biomaterials  6‐bromoindirubin‐3′  ‐oxime  proliferation  pluripotency  regenerative medicine
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