title: Agonism of Wnt-β-catenin signalling promotes mesenchymal stem cell (MSC) expansion.
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.
authors.affiliation: Departments of Biomedical Engineering, Chemical Engineering and Orthopaedics and Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hoffman
authors.affiliation: Departments of Biomedical Engineering, Chemical Engineering and Orthopaedics and Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Danielle S W
authors.initials: DS
authors.lastname: Benoit
mesh_terms: D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D006868:Hydrolysis; D007211:Indoles / Q000737:chemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008809:Mice, Inbred C3H; D010006:Osteoblasts / Q000166:cytology; D010091:Oximes / Q000737:chemistry; D044968:Regenerative Medicine / Q000379:methods; D051153:Wnt Proteins / Q000819:agonists / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000819:agonists / Q000378:metabolism*
chemical_list: C483321:6-bromoindirubin-3'-oxime; D020100:Hydrogels; D007211:Indoles; D010091:Oximes; D051153:Wnt Proteins; D051176:beta Catenin
keywords: 6-bromoindirubin-3′-oxime; hydrogel biomaterials; mesenchymal stem cells; pluripotency; proliferation; regenerative medicine
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