Restorative pontential of fetal striatal multipotent progenitors in Huntington disease

Object: Foetal graft transplantation has emerged as a potential repair therapy for Huntington’s disease (HD). Here is reported the identification and characterization of striatal multipotent progenitors in human foetal ganglionic eminence that in vitro have the capacity for self-renewal and multilineage differentiation. Methods: Four HD patients underwent bilateral human foetal striatal transplantation in two sessions 2-3 months apart. Small blocks of whole ganglionic eminencies of 9-12 weeks old foetuses were processed to obtain cell suspension and then stereotactically grafted in the caudate head and in the pre and post-commissural putamen. A small aliquot of final suspension was processed for morphological and in vitro studies. Gene expression analysis of the graft tissue was also performed to correlate striatal differentiation, proliferation, migration and neural maintenance potentials with graft development. Results: The study provides an “in vivo“ evidence of generation of new tissue with the anatomical features of the corresponding mature structure.When transplanted into the striatum of HD patients these cells developed and generated new metabolically active tissue with striatal-like imaging features. In addition, new viable tissue connected the neogenerated tissue in the site of the striatum with frontal cortex and with the ventral striatal region. The anlagen development in the host brain was accompanied by beneficial effects on the clinical course of the disease. Conclusions: The ability of these cells to develop and migrate after intracerebral transplantation, together with their apparent lack of tumorigenicity, suggests their restorative potential in the treatment of HD.