Human umbilical cord blood treatment in a mouse model of ALS: optimization of cell dose.
BACKGROUND
Amyotrophic Lateral Sclerosis (ALS) is a multicausal disease characterized by motor neuron degeneration in the spinal cord and brain. Cell therapy may be a promising new treatment for this devastating disorder. We recently showed that a single low dose (10(6) cells) of mononuclear human umbilical cord blood (MNC hUCB) cells administered intravenously to G93A mice delayed symptom progression and modestly prolonged lifespan. The aim of this pre-clinical translation study is to optimize the dose of MNC hUCB cells to retard disease progression in G93A mice. Three different doses of MNC hUCB cells, 10x10(6), 25x10(6) and 50x10(6), were administered intravenously into pre-symptomatic G93A mice. Motor function tests and various assays to determine cell effects were performed on these mice.


RESULTS
Our results showed that a cell dose of 25x10(6) cells significantly increased lifespan of mice by 20-25% and delayed disease progression by 15%. The most beneficial effect on decreasing pro-inflammatory cytokines in the brain and spinal cord was found in this group of mice. Human Th2 cytokines were found in plasma of mice receiving 25x10(6) cells, although prevalent human Th1 cytokines were indicated in mice with 50x10(6) cells. High response of splenic cells to mitogen (PHA) was indicated in mice receiving 25x10(6) (mainly) and 10x10(6) cells. Significantly increased lymphocytes and decreased neutrophils in the peripheral blood were found only in animals receiving 25x10(6) cells. Stable reduction in microglia density in both cervical and lumbar spinal cords was also noted in mice administered with 25x10(6) cells.


CONCLUSIONS
These results demonstrate that treatment for ALS with an appropriate dose of MNC hUCB cells may provide a neuroprotective effect for motor neurons through active involvement of these cells in modulating the host immune inflammatory system response.
Center of Excellence for Aging & Brain Repair, College of Medicine, University of South Florida, Tampa, Florida, United States of America. sgarbuzo@health.usf.edu
Svitlana
S
Garbuzova-Davis
Cyndy Davis
CD
Sanberg
Nicole
N
Kuzmin-Nichols
Alison E
AE
Willing
Carmelina
C
Gemma
Paula C
PC
Bickford
Christina
C
Miller
Robert
R
Rossi
Paul R
PR
Sanberg
D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005312:Fetal Blood; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D016207:Cytokines