Beneficial Effects of Transplanted Human Bone Marrow Endothelial Progenitors on Functional and Cellular Components of Blood-Spinal Cord Barrier in ALS Mice

Convincing evidence of blood-spinal cord barrier (BSCB) alterations has been demonstrated in amyotrophic lateral sclerosis (ALS) and barrier repair is imperative to prevent motor neuron dysfunction. We showed benefits of human bone marrow-derived CD34+ cells (hBM34+) and endothelial progenitor cells (hBM-EPCs) intravenous transplantation into symptomatic G93A SOD1 mutant mice on barrier reparative processes. These gains likely occurred by replacement of damaged endothelial cells, prolonging motor neuron survival. However, additional investigations are needed to confirm the effects of administered cells on integrity of the microvascular endothelium. The aim of this study was to determine tight junction protein levels, capillary pericyte coverage, microvascular basement membrane, and endothelial filamentous actin (F-actin) status in spinal cord capillaries of G93A SOD1 mutant mice treated with human bone marrow-derived stem cells. Tight junction proteins were detected in the spinal cords of cell-treated versus non-treated mice via Western blotting at four weeks after transplant. Capillary pericyte, basement membrane laminin, and endothelial F-actin magnitudes were determined in cervical/lumbar spinal cord tissues in ALS mice, including controls, by immunohistochemistry and fluorescent staining. Results showed that cell-treated versus media-treated ALS mice substantially increased tight junction protein levels, capillary pericyte coverage, basement membrane laminin immunoexpressions, and endothelial cytoskeletal F-actin fluorescent expressions. The greatest benefits were detected in mice receiving hBM-EPCs versus hBM34+ cells. These study results support treatment with a specific cell type derived from human bone marrow toward BSCB repair in ALS. Thus, hBM-EPCs may be advanced for clinical applications as a cell-specific approach for ALS therapy through restored barrier integrity.