Transgenic reporter mice as tools for studies of transplantability and connectivity of dopamine neuron precursors in fetal tissue grafts.
Cell therapy for Parkinson's disease (PD) is based on the idea that new midbrain dopamine (mDA) neurons, implanted directly into the brain of the patient, can structurally and functionally replace those lost to the disease. Clinical trials have provided proof-of-principle that the grafted mDA neurons can survive and function after implantation in order to provide sustained improvement in motor function for some patients. Nonetheless, there are a number of issues limiting the application of this approach as mainstream therapy, including: the use of human fetal tissue as the only safe and reliable source of transplantable mDA neurons, and variability in the therapeutic outcome. Here we review recent progress in this area from investigations using rodent models of PD, paying particular attention to the use of transgenic reporter mice as tools for neural transplantation studies. Cell type-specific expression of reporter genes, such as green fluorescent protein, affords valuable technical advantages in transplantation experiments, such as the ability to selectively isolate specific cell fractions from mixed populations prior to grafting, and the unambiguous visualization of graft-derived dopamine neuron fiber patterns after transplantation. The results from these investigations have given new insights into the transplantability of mDA precursors as well as their connectivity after grafting and have interesting implications for the development of stem cell based approaches for the treatment of PD.
Thompson
Lachlan H
LH
Florey Neuroscience Institutes, University of Melbourne, Parkville, Victoria, Australia. lachlan.thompson@florey.edu.au
Björklund
Anders
A
D000818:Animals; D053686:Fetal Stem Cells / Q000166:cytology / Q000637:transplantation*; D006801:Humans; D008636:Mesencephalon / Q000378:metabolism / Q000637:transplantation; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000637:transplantation*; D010300:Parkinson Disease / Q000601:surgery*; D033581:Stem Cell Transplantation / Q000379:methods*