Bone marrow-derived mesenchymal stem cell transplantation for chronic spinal cord injury in rats: comparative study between intralesional and intravenous transplantation

Abstract

Study design: Animal experimental study.

Objective: To present experimental evidence for mesenchymal cell therapy for spinal cord injury (SCI).

Summary of background data: Prior to clinical application of stem cell therapy for SCI, many critical issues have to be addressed including efficiency, safety, method of transplantation, and differentiation of the transplanted cells.

Methods: Chronic contusive SCI was induced in 36 Sprague-Dawley rats and randomly assigned to the intralesional (IL), intravenous (IV), or control groups. At 6 weeks post injury, allogenic mesenchymal stem cells (MSCs, 1 × 10 cells) were transplanted either intralesionally or intravenously for the intervention groups. Engraftment of the transplanted MSCs was evaluated with PKH 26 staining. Differentiation was evaluated using double stain with neuronal and glial cell markers. Brain-derived neurotrophic factor and nerve growth factor (NGF) were used for neurotrophic factor expression. Basso, Beattie, and Bresnahan locomotor rating scale was used for evaluation of functional recovery.

Results: The estimated engraftment percentage of the transplanted cells in the IL group and IV group were 36.5%, and 15.5%, respectively. The engraftment of the transplanted MSCs was higher in the IL group than in the IV group. Most of the transplanted MSCs were colocalized with GFAP in both transplantation groups. Brain-derived neurotrophic factor and NGF expression (Western blot and real-time polymerase chain reaction) in the injured spinal cord was higher in both transplanted groups compared with those in the control group. At 6 weeks post transplantation, the mean Basso, Beattie, and Bresnahan locomotor scales in the IL, IV, and control groups were 5.63 ± 0.89, 5.63 ± 1.03, and 2.88 ± 0.44, respectively. The functional recovery seen in the rats that underwent transplantation was significantly better than that in the control group (P < 0.05).

Conclusion: Although the number of engrafted cells and expression of neurotrophic factors were lower in the IV group than those in the IL group, both IL and IV transplantation of MSC in the chronic SCI gave a significant clinical improvement. However, there were no differences in differentiation of the transplanted cells between the IL group and IV group. Astrocytic differentiation of the transplanted cells was predominant.

Level of evidence: N/A.