Abstract
Amyotrophic lateral sclerosis (ALS) is a multifactorial disease with one of these factors being an impaired blood-spinal cord barrier (BSCB). In order to block harmful components in systemic circulation from accessing the CNS, barrier damage needs alleviation. Recently, we found that symptomatic ALS animals treated with intravenously delivered human bone marrow-derived CD34+ (hBM34+) cells or endothelial progenitor cells (hBMEPCs) showed delayed disease progression for 4 weeks post-transplant via BSCB repair. However, despite noted benefits from transplanted human bone marrow-derived stem cells, long-term effects of transplanted cells in ALS mice remain undetermined. This study aimed to determine prolonged effects of single equal doses of hBM34+ cells and hBMEPCs systemically transplanted into symptomatic G93A SOD1 mice on behavioral disease outcomes and mouse lifespan. Results showed that transplanted hBMEPCs better ameliorated disease behavioral outcomes than hBM34 + cells until near end-stage disease and significantly increased lifespan vs. media-treated mice. These results provide important evidence that transplanted hBMEPCs prolonged functional benefits and extended survival of ALS mice, potentially by repairing the damaged BSCB. However, due to modestly increased lifespan of hBMEPC-treated mice, repeated cell transplants into symptomatic ALS mice may more effectively delay motor function deficit and extend lifespan by continuous reparative processes via replacement of damaged endothelial cells during disease progression.
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