Adult Skin-derived Neural Precursors Engraft into the Hippocampus and Rescue Memory Dysfunction.

Repopulation of brain circuits by neural precursors is a promising therapeutic strategy under investigation in animal models of neurodegeneration. Major limitations include a propensity for glial differentiation in vivo and the use of transgenic modifications that restrict rapid clinical translation. Here, we detail a two-step method for producing adult neural precursor cells from a small autologous skin sample. These cells express neural stem/progenitor cell markers, are highly homogenous, rate-limited by virtue of low number of maximal cell doublings, and differentiate almost exclusively into neurons without expression of glial molecular markers. These characteristics are recapitulated in vivo following transplantation in the aged rodent brain. Cell transplantation into the hippocampus is safe and leads to widespread neuronal engraftment and synaptogenesis. Donor cells display appropriate anatomical architecture, become electrophysiologically active and establish synaptic connections within the host brain. Moreover, selective hippocampally-dependent place recognition memory deficits are reversed. Adult skin-derived neural precursors overcome many of the limitations present in current stem cell therapies. Accordingly, these cells have potential use as a cell therapy treatment for the regeneration of depleted or dysfunctional neuronal circuits in patients with neurodegenerative disorders. Primary cell culture was derived from canine fibroblast, brain and skin samples, RNA extract and put forward for Affymetrix array gene expression profiling