Human multipotent stromal cells (MSCs) increase neurogenesis and decrease atrophy of the striatum in a transgenic mouse model for Huntington's disease.
BACKGROUND
Implantation of human multipotent stromal cells from bone marrow (hMSCs) into the dentate gyrus of the hippocampus of mice was previously shown to stimulate proliferation, migration and neural differentiation of endogenous neural stem cells. We hypothesized that hMSCs would be beneficial in a mouse model of Huntington disease (HD) due to these neurogenic effects.


RESULTS
We implanted hMSCs into the striatum of transgenic mice (N171-82Q) that are a model for HD. The implanted hMSCs rapidly disappeared over 3 to 15 days. However, they increased proliferation and neural differentiation of endogenous neural stem cells for up to 30 days. They also increased neurotrophic signaling and decreased atrophy of the striatum in 3-month old HD mice implanted with hMSCs one month earlier.


CONCLUSIONS
The results therefore suggested that neural implantation of hMSCs may be of benefit in HD but a number of parameters of dose, treatment schedule, and route of administration need to be optimized.
Snyder
Brooke R
BR
Yerkes National Primate Research Center, Atlanta, Georgia, United States of America.
Chiu
Andrew M
AM
Prockop
Darwin J
DJ
Chan
Anthony W S
AW
D000818:Animals; D001284:Atrophy / Q000601:surgery; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D003342:Corpus Striatum / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000473:pathology / Q000601:surgery*; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D009414:Nerve Growth Factors / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction; D033581:Stem Cell Transplantation / Q000379:methods*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D013997:Time Factors; D014183:Transplantation, Heterologous
D009414:Nerve Growth Factors; D049452:Green Fluorescent Proteins