Faculty Collaboration Database

Transplanted neurally modified bone marrow-derived mesenchymal stem cells promote tissue protection and locomotor recovery in spinal cord injured rats. Neurorehabil Neural Repair 2011;25(9):873-80

Date

08/17/2011

Pubmed ID

21844281

DOI

10.1177/1545968311416823

Scopus ID

2-s2.0-80054030150 (requires institutional sign-in at Scopus site)   52 Citations

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.

Author List

Alexanian AR, Fehlings MG, Zhang Z, Maiman DJ

Author

Arshak R. Alexanian VMD, PhD Adjunct Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Bone Marrow Transplantation
Female
Humans
Mesenchymal Stem Cell Transplantation
Neurogenesis
Paralysis
Primary Cell Culture
Rats
Rats, Sprague-Dawley
Spinal Cord Injuries
Transplantation, Heterologous
Treatment Outcome