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

PLoS One

Nicole Kuzmin-Nichols¹  Cyndy D. Sanberg¹  Shazia Mitha¹  Subatha Suthakaran¹  Svitlana Garbuzova-Davis¹  David J. Eve¹  Paul R. Sanberg¹  Santhia Mirtyl²  Maria C. O. Rodrigues³  Shanna Turner⁴  Jasmine Sodhi⁵ 

[1] Center of Excellence for Aging and Brain Repair, University of South Florida, College of Medicine, Tampa, Florida, United States of America;Department of Molecular Pharmacology and Physiology, University of South Florida, College of Medicine, Tampa, Florida, United States of America;Department of Neurosurgery and Brain Repair, University of South Florida, College of Medicine, Tampa, Florida, United States of America;Department of Pathology and Cell Biology, University of South Florida, College of Medicine, Tampa, Florida, United States of America;Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil

关键词: Motor neurons;    Spinal cord;    Mouse models;    Astrocytes;    Microglial cells;    Body weight;    Blood;    Umbilical cord;   

DOI  :  10.1371/journal.pone.0031254

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Background 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. Methodology/Principal Findings 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. Conclusions/Significance 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.

【 授权许可】

CC BY