Transplantation of human neural precursor cells in the 6-OHDA lesioned rats: Effect of immunosuppression with cyclosporine A

Restorative approaches in Parkinson's Disease: Which cell type wins the race?

“…These studies further demonstrated that implantation of precursor-derived dopaminergic neurons from rodents leads to histological, biochemical and functional recovery in animal models of PD [85,99,105,107,108], but only recent studies used NSCs after long-term expansion [94]. After the reports on long-term expansion and functional dopaminergic differentiation of human midbrain NSCs [77,87,95,96], we were able to demonstrate functional and histological reconstitution after transplanting these cells into the striatum of parkinsonian rats [84]. Moreover, we found only mild immunoreactions and no tumor formation.…”

“…Most in vitro studies regarding fetal midbrain NSCs involved rodent embryos at embryonic day (E)14 to E15 [65,76,80,82], while on human midbrain material, samples of 6-9 weeks post-fertilization were used [77,[83][84][85][86][87]. Gensburger and co-workers (1987) found that fibroblast growth factor-2 (FGF-2) could induce proliferation of neural precursors in embryonic hippocampal cultures initiating a new field of cell culture experiments studying proliferation of neural precursors in vitro [88].…”

The Role of Immunosuppression in the Transplantation of Allogenic Neural Precursors Derived from Human Pluripotent Stem Cells for Parkinson’s Disease

“…Although cyclosporine was the first calcineurin inhibitor that revolutionized immunosuppression by strongly reducing the rate of rejection in solid organ transplantation and still remains very effective, it is currently supplanted by tacrolimus. Previous data have suggested that cyclosporine could be deleterious in the maturation process of NPC [6,7], when other publications suggest that cyclosprorine could be beneficial [8,9]. Most of the published data have concluded that cycloporine had direct effect on neuron differentiation, but protected the engrafted cells from rejection [8,9].…”

The Pharmacology of Regenerative Medicine

“…The effect of various cell sources have been investigated in animal models of PD, as well as in humans, and these include, embryonic stem (ES) cells (Freed et al, 2001;Kim et al, 2002, see Lindvall and, induced pluripotent stem (iPS) cells (Wernig et al, 2008), fetal and adult brain-derived neural stem cells (NSC; Hermann et al, 2006;Schwarz et al, 2006), mesenchymal stem cells (MSC; Hellmann et al, 2006;Cova et al, 2010), and amniotic fluid stem (AFS) cells (Donaldson et al, 2009). In an interesting application of regenerative pharmacology, neural progenitors generated from pluripotent stem cells in culture were induced to give rise to dopaminergic neurons, which hold therapeutic potential for PD.…”