Neurotrophin-3 Stimulates Migration of Mesenchymal Stem Cells Overexpressing TrkC

Y.F.      Chen; X.      Zeng; K.      Zhang; B.Q.      Lai; E.A.      Ling; Y.S.      Zeng

Abstract

Background and Purpose: Transplantation/infusion of mesenchymal stem cells (MSCs) is a promising new approach for treatment of spinal cord injury (SCI). Considering some defined chemokines of MSCs that may have adverse side effects in SCI repair, it is therefore desirable to search for a new chemokine, which should not only be harmless to the host, but also would attract more MSCs to the injury area of spinal cord. This study sought to demonstrate if neurotrophin- 3 (NT-3) would attract migration of MSCs with overexpressing tyrosine kinase C (TrkC) a NT-3 receptor. Experimental Approach: A micropipette containing NT-3 was placed in cell culture dish. After this, movement of TrkC gene modified MSCs was monitored for 240 min under an inverted microscope equipped with an imaging system. In vivo, a gelatin sponge scaffold containing TrkC gene modified MSCs was transplanted into the injury area of transected rat spinal cord. Following this, replication-deficient recombinant adenoviral vectors carrying human NT-3 gene (Ad-NT-3) was injected 1 mm caudal to the transplantation site to create an NT-3 enriched area. Key Results: The results showed that TrkC overexpressing MSCs migrated actively towards the source of NT-3 in the NT-3+TrkC-GFP-MSCs group in vitro. A similar phenomenon was not observed in the control groups. In vivo, transplanted MSCs overexpressing TrkC migrated into the NT-3 enriched area. The incidence of migrating MSCs as well as migration distance was significantly higher than the control groups. Conclusion and Implications: The present results suggest that NT-3 may play a role in attracting MSCs with its high affinity for TrkC as a chemokine receptor.

Keywords: Neurotrophin-3, tyrosine kinase C, chemotaxis, chemokine, bone marrow mesenchymal stem cells, spinal cord injury, cell therapy, cell transplantation.