Co-transplantation of mesenchymal and neural stem cells and overexpressing stromal-derived factor-1 for treating spinal cord injury

• Published in: Brain research Vol. 1672; pp. 91 - 105
• Main Authors: Stewart, Andrew N., Kendziorski, Griffin, Deak, Zachary M., Brown, Dara J., Fini, Matthew N., Copely, Katherine L., Rossignol, Julien, Dunbar, Gary L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2017
• Subjects: Animals; Axons - metabolism; Chemokine CXCL12 - metabolism; Chemokine CXCL12 - therapeutic use; Co-transplantation; CXCL12; Disease Models, Animal; Female; Mesenchymal stem cell; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - physiology; Neural Stem Cells - metabolism; Neural Stem Cells - transplantation; Neuronal stem cell; Neurons - metabolism; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord - metabolism; Spinal Cord Injuries - therapy; Spinal cord injury; Stromal derived factor-1; Mesenchymal stem cell; BBB; Neuronal stem cell; NF-70; tdTomato; Stromal derived factor-1; SDF-1; CXCR4; Spinal cord injury; Co-transplantation; GFP; NSCs; MSCs; CXCL12; SCI
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2017.07.005

•We used mesenchymal (MSCs) and neural (NSCs) stem cells to treat spinal cord injury.•MSCs were modified to overexpress stromal-derived factor-1 (SDF-1).•Co-transplants of MSCs that overexpress SDF-1 with NSCs improved behavioral outcomes.•Tumors were found in some MSC-NSC co-transplanted rats. Genetic engineering of mesenchymal stem cells (MSCs) and neuronal stem cells (NSCs) has been used to treat spinal cord injuries (SCI). As a mechanism of therapy, MSCs secrete high amounts of trophic factors, while NSCs can differentiate into neuronal lineages and aid in tissue replacement. Additionally, the forced overexpression of secreted proteins can enhance the secretome of transplanted cells, which can increase therapeutic efficacy. This study utilized a combinational treatment consisting of MSCs, NSCs, and the forced overexpression of the chemokine stromal-derived factor-1 (SDF-1) from MSCs (SDF-1-MSCs) as treatment in a rat model of SCI. Transplants occurred at 9-days post-injury, and motor functions were evaluated for 7-weeks post-injury. White matter sparing and axon densities surrounding the lesions were quantified. Findings from this study demonstrate that co-transplanting SDF-1-MSCs with NSCs improved motor functions and enhanced axon densities surrounding the lesion. However, no improvements in white matter sparing were found and tumors were found in some of the animals that received co-transplantations with either SDF-1-MSCs and NSCs or unmodified-MSCs and NSCs, but not in any animal treated with a single cell type. This study offers evidence that providing SDF-1 to NSCs, through the forced expression from MSCs, can enhance the therapeutic potential of the graft, but developing a safe means of doing this requires further work.