The therapeutic potential of human mesenchymal/multipotent stem/progenitor cells in the striatum of Huntington diseased mice
Description
Human Mesenchymal Stern/Multipotent Progenitor Cells (hMSCs have previously been shown to potentiate neurogenesis after implantation into a neurogenic niche of the adult mouse brain1. This study determined whether or not this effect will persist in a disease model affecting the Central Nervous System (CNS), specifically in N171-82Q Huntington's disease (HD) mice. Twenty four hours after implantation into the striatum, only approximately 15% of the grafted hMSCs remained. Only roughly 5% of the grafted cells survived to 5 days and no intact cells were detected by 15 days post-implantation. Conversely, endogenous cell proliferation increased after hMSC implantation. Five to fifteen days post-implantation there were significantly more dividing cells in the MSC-implanted striatum than in the PBS-injected striatum. These new cells survived and differentiated into mature neural cells by 30 days. During the first 30 days post-implantation there was also an influx of pre-existing neural progenitor cells (NPCs) and neurons to the site of the graft, which did not occur in response to the sham, Phosphate Buffered Saline (PBS) injection. The hMSC graft also upregulated neurotrophic signaling in the striatum. One possible conclusion from this research is that implantation of hMSCs increases neurotrophin signaling which promotes neurogenesis, neural differentiation, neuronal recruitment, and cell survival. hMSCs were also bilaterally implanted into the striatum of N171-82Q HD mice at both 6 and 8 weeks of age. Implantation of hMSCs improved the pathology associated with HD. There was a decrease in the volume of the lateral ventricles and a significant increase in striatal volume after MSC transplantation that did not occur after PBS injection. Grafting hMSCs bilaterally in the striatum at 8 weeks also prevented late life decline in rotarod performance. MSC transplantation did not significantly effect survival. MSCs improve HD pathology and phenotype, without accelerating survival, and should, therefore, be considered as a potential treatment for HD