Transplanted Neurally Modified Bone Marrow–Derived Mesenchymal Stem Cells Promote Tissue Protection and Locomotor Recovery in Spinal Cord Injured Rats

Abstract

Background. Stem cell–based therapy for repair and replacement of lost neural cells is a promising treatment for central nervous system (CNS) diseases. Bone marrow (BM)–derived mesenchymal stem cells (MSCs) can differentiate into neural phenotypes and be isolated and expanded for autotransplantation with no risk of rejection. Objective. The authors examined whether transplanted neurally induced human MSCs (NI hMSCs), developed by a new procedure, can survive, differentiate, and promote tissue protection and functional recovery in injured spinal cord (ISC) rats. Methods. Neural induction was achieved by exposing cells simultaneously to inhibitors of DNA methylation, histone deacetylation, and pharmacological agents that increased cAMP levels. Three groups of adult female Sprague-Dawley rats were injected immediately rostral and caudal to the midline lesion with phosphate-buffered saline, MSCs, or NI hMSCs, 1 week after a spinal cord impact injury at T-8. Functional outcome was measured using the Basso Beattie Bresnahan (BBB) locomotor rating scale and thermal sensitivity test on a weekly basis up to 12 weeks postinjury. Graft integration and anatomy of spinal cord was assessed by stereological, histochemical, and immunohistochemical techniques. Results. The transplanted NI hMSCs survived, differentiated, and significantly improved locomotor recovery of ISC rats. Transplantation also reduced the volume of lesion cavity and white matter loss. Conclusion. This method of hMSC modification may provide an alternative source of autologous adult stem cells for CNS repair.