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

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