Multiple Intravenous Administrations of Human Umbilical Cord Blood Cells Benefit in a Mouse Model of ALS

Center of Excellence for Aging and Brain Repair, University of South Florida, College of Medicine, Tampa, Florida, United States of America.
PLoS ONE (Impact Factor: 3.23). 02/2012; 7(2):e31254. DOI: 10.1371/journal.pone.0031254
Source: PubMed


A promising therapeutic strategy for amyotrophic lateral sclerosis (ALS) is the use of cell-based therapies that can protect motor neurons and thereby retard disease progression. We recently showed that a single large dose (25 × 10⁶ cells) of mononuclear cells from human umbilical cord blood (MNC hUCB) administered intravenously to pre-symptomatic G93A SOD1 mice is optimal in delaying disease progression and increasing lifespan. However, this single high cell dose is impractical for clinical use. The aim of the present pre-clinical translation study was therefore to evaluate the effects of multiple low dose systemic injections of MNC hUCB cell into G93A SOD1 mice at different disease stages.
Mice received weekly intravenous injections of MNC hUCB or media. Symptomatic mice received 10⁶ or 2.5 × 10⁶ cells from 13 weeks of age. A third, pre-symptomatic, group received 10⁶ cells from 9 weeks of age. Control groups were media-injected G93A and mice carrying the normal hSOD1 gene. Motor function tests and various assays determined cell effects. Administered cell distribution, motor neuron counts, and glial cell densities were analyzed in mouse spinal cords. Results showed that mice receiving 10⁶ cells pre-symptomatically or 2.5 × 10⁶ cells symptomatically significantly delayed functional deterioration, increased lifespan and had higher motor neuron counts than media mice. Astrocytes and microglia were significantly reduced in all cell-treated groups.
These results demonstrate that multiple injections of MNC hUCB cells, even beginning at the symptomatic disease stage, could benefit disease outcomes by protecting motor neurons from inflammatory effectors. This multiple cell infusion approach may promote future clinical studies.

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    • "In our previous study of proliferation in the aging hippocampus with the MNC (Bachstetter et al. 2008), these cells were effective in inducing proliferation at these doses when delivered in combination (i.e., the whole MNC). To alter the dose of the individual cells such that all cells were delivered at 10 6 would have also been problematic, since there are dose-dependent effects of cell delivery and too many cells can have detrimental effects (Vendrame et al. 2004; Garbuzova-Davis et al. 2012). Therefore, 4.8× 10 5 cells were injected in the CD4+ group, 1.3×10 5 in the CD8+ group, 1.4×10 5 in the CD14+ group, 0.2× 10 5 in the CD133+ group, and 1×10 6 in the HUCB MNC group. "
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