Engineered Mesenchymal Stem Cells with Enhanced Tropism and Paracrine Secretion of Cytokines and Growth Factors to Treat Traumatic Brain Injury

Traumatic brain injury (TBI) is the leading cause of death and disability worldwide. Mesenchymal stem cells (MSCs) are promising for the treatment of various diseases and injuries. Many strategies have been applied to attract MSCs to injury site after systemic infusion. In this study, we evidenced that the CXC chemokine receptor 4 (CXCR4)-SDF1α (stromal cell-derived factor 1α) axis in engineered MSCs serves not only to attract MSC migration to TBI but also to activate Akt kinase signaling pathway in MSCs to promote paracrine secretion of cytokines and growth factors. This leads to enhanced vasculogenesis and neuroprotection at the boundary of TBI for improved blood supply, recovery of axon connectivity, and behavioral ability and results in positive feedback loop to enhance additional MSC tropism to injury. These findings indicate a new aspect of SDF1α in mediating CXCR4 engineered MSCs for brain trauma homing and recovery. This potential mechanism may be applicable to other injuries, where CXCR4-SDF1α interaction is highly associated.