442737 Transdifferentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Schwann-like Cells That Secrete Neurotrophic Factors and Promote Differentiation of PC12-Trkb Cells

Monday, November 9, 2015
Exhibit Hall 1 (Salt Palace Convention Center)
Pratish Adhikari, Iowa State University, Ames, IA

Transplantation of Schwann cells (SCs) has been shown to improve peripheral nerve regeneration following nerve injuries. However, harvesting of Schwann cells requires an additional surgery and sacrifice of a donor nerve resulting in donor site morbidity. Additionally, Schwann cells are difficult to maintain in primary culture. As an alternative cell source, a number of studies have demonstrated that multipotent mesenchymal stem cells (MSCs) derived from adult bone marrow are capable of transdifferentiation into SC-like cells. In this study, undifferentiated rat mesenchymal stem cells (uMSCs) and transdifferentiated mesenchymal stem cells (tMSCs) were co-cultured with PC12-TrkB cells to test their SC-like properties. PC12-TrkB cells, a noradrenergic clonal cell line genetically modified to express TrkB receptors (gift from M. Chao, NYU) and respond to nerve growth factor (NGF) or brain derived neurotrophic factor. Transdifferentiated MSCs co-cultured with PC12-TrkB cells expressed SC-markers and secreted higher levels of NGF as compared to uMSCS co-cultured with PC12-TrkB cells. Transdifferentiated MSCs co-cultured with PC12-TrkB cells also induced a greater neurite outgrowth as compared to uMSCs co-cultured with PC12-TrkB cells, showing the functional benefit associated with usage of these SC-like cells. With this study, we were able to show molecular changes in MSCs following transdifferentiation and functional benefits by performing co-cultures with PC12-TrkB cells. Future studies will employ tMSCs within nerve regeneration conduits for in vivo studies for peripheral nerve regeneration.

Financial support provided by: The US Army Medical Research and Materiel Command #W81XWH-11-1-0700; The Stem Cell Research Fund, Iowa State University

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