Human Umbilical Cord Blood Treatment in a Mouse Model of ALS: Optimization of Cell DoseReportar como inadecuado




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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 106 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, 10×106, 25×106 and 50×106, were administered intravenously into pre-symptomatic G93A mice. Motor function tests and various assays to determine cell effects were performed on these mice.

Methodology-Principal Findings

Our results showed that a cell dose of 25×106 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 25×106 cells, although prevalent human Th1 cytokines were indicated in mice with 50×106 cells. High response of splenic cells to mitogen PHA was indicated in mice receiving 25×106 mainly and 10×106 cells. Significantly increased lymphocytes and decreased neutrophils in the peripheral blood were found only in animals receiving 25×106 cells. Stable reduction in microglia density in both cervical and lumbar spinal cords was also noted in mice administered with 25×106 cells.

Conclusions-Significance

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.



Autor: Svitlana Garbuzova-Davis , Cyndy Davis Sanberg, Nicole Kuzmin-Nichols, Alison E. Willing, Carmelina Gemma, Paula C. Bickford, Chr

Fuente: http://plos.srce.hr/



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