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Transplantation of subventricular zone neural precursors induces an endogenous precursor cell response in a rat model of Parkinson's disease
Author(s) -
Madhavan Lalitha,
Daley Brian F.,
Paumier Katrina L.,
Collier Timothy J.
Publication year - 2009
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.22033
Subject(s) - subventricular zone , transplantation , glial cell line derived neurotrophic factor , substantia nigra , neural stem cell , neurotrophic factors , neurogenesis , biology , neuroscience , neuroprotection , precursor cell , endogeny , stem cell , dopamine , microbiology and biotechnology , medicine , cell , endocrinology , dopaminergic , biochemistry , receptor
Realistically, future stem cell therapies for neurological conditions including Parkinson's disease (PD) will most probably entail combination treatment strategies, involving both the stimulation of endogenous cells and transplantation. Therefore, this study investigates these two modes of neural precursor cell (NPC) therapy in concert in order to determine their interrelationships in a rat PD model. Human placental alkaline phosphatase (hPAP)‐labeled NPCs were transplanted unilaterally into host rats which were subsequently infused ipsilaterally with 6‐hydroxydopamine (6‐OHDA). The reaction of host NPCs to the transplantation and 6‐OHDA was tracked by bromodeoxyuridine (BrdU) labeling. Two weeks after transplantation, in animals transplanted with NPCs we found evidence of elevated host subventricular zone NPC proliferation, neurogenesis, and migration to the graft site. In these animals, we also observed a significant preservation of striatal tyrosine hydroxylase (TH) expression and substantia nigra TH cell number. We have seen no evidence that neuroprotection is a product of dopamine neuron replacement by NPC‐derived cells. Rather, the NPCs expressed glial cell line‐derived neurotrophic factor (GDNF), sonic hedgehog (Shh), and stromal cell‐derived factor 1 alpha (SDF1α), providing a molecular basis for the observed neuroprotection and endogenous NPC response to transplantation. In summary, our data suggests plausible synergy between exogenous and endogenous NPC actions, and that NPC implantation before the 6‐OHDA insult can create a host microenvironment conducive to stimulation of endogenous NPCs and protection of mature nigral neurons. J. Comp. Neurol. 515:102–115, 2009. © 2009 Wiley‐Liss, Inc.