Redmond DE Jr et al. (2007) Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells. Proc Natl Acad Sci USA 104: 12175–12180

In a recent paper, Redmond et al. report that transplantation of human neural stem cells (hNSCs) leads to functional improvement in a primate model of severe Parkinson's disease. Importantly, their study indicates that the stem cells seem to act not only by replacement of dopaminergic cells, but also by supporting multiple endogenous repair systems.

In the study, undifferentiated hNSCs were implanted into the right substantia nigra (SN) and the bilateral caudate nuclei of adult African green monkeys with severe Parkinson's disease. Four months after implantation, monkeys treated with hNSCs showed significant behavioral and functional improvements, measured by a Parkinson's factor score, compared with those that underwent a sham operation (P <0.05). Histological examination demonstrated robust survival and migration of engrafted hNSCs, which differentiated into various neural stem cell types. A small number of graft-derived cells were found in the lesioned host SN, where they expressed markers consistent with a dopaminergic phenotype. Many other cells migrated along the nigrostriatal pathway, where they closely associated with host-derived cells, and differentiated into astrocytic cells expressing factors that protect dopaminergic cells. As well as preserving the host nigrostriatal circuitry, hNSC-derived cells were associated with a normalizing effect on the size and number of endogenous neurons in the SN, as well as normalization of α-synuclein aggregation.

The authors hypothesize that intrinsic signals in the lesioned host might direct differentiation of hNSCs to promote homeostasis of SN neurons and their nigrostriatal projections, thereby restoring function.