Multiple intravenous administrations of human umbilical cord blood cells benefit in a mouse model of ALS.
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.


RESULTS
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
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.
Center of Excellence for Aging and Brain Repair, University of South Florida, College of Medicine, Tampa, Florida, United States of America. sgarbuzo@health.usf.edu
Svitlana
S
Garbuzova-Davis
Maria C O
MC
Rodrigues
Santhia
S
Mirtyl
Shanna
S
Turner
Shazia
S
Mitha
Jasmine
J
Sodhi
Subatha
S
Suthakaran
David J
DJ
Eve
Cyndy D
CD
Sanberg
Nicole
N
Kuzmin-Nichols
Paul R
PR
Sanberg
D000690:Amyotrophic Lateral Sclerosis / Q000628:therapy*; D000818:Animals; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000637:transplantation*; D006801:Humans; D018836:Inflammation Mediators; D007262:Infusions, Intravenous; D051379:Mice; D009046:Motor Neurons; D016896:Treatment Outcome
D018836:Inflammation Mediators