For Researchers > Basic/Pre-Clinical Research > Parkinson's Disease > Stem Cell Grafts in Animal Models of Parkinson's

Stem Cell Grafts in Animal Models of Parkinson's

One promising new therapy for Parkinson's disease (PD) involves the replacement of degenerated nigrostriatal neurons with those derived from transplanted fetal mesencephalic tissue. Although this approach has often yielded remarkable recovery of function in rats and monkeys, results in clinical trials with PD patients have been less consistent. At issue is the relative inability to standardize a number of critical factors in human fetal transplants, including the age, type, number and integrity of cells being grafted. Consequently, finding more reliable sources of dopaminergic (DA) tissue for transplantation has become increasingly important. One direction has been to search for a line of readily available, well-characterized continually self-renewing stem or precursor cells that possess the capacity to differentiate into DA neurons, ideally spontaneously and with little manipulation. This would provide an inexhaustible and uniform source of replacement tissue.

Toward that end, our preliminary findings demonstrate that mouse and human embryonic stem or progenitor cells can differentiate exclusively into neurons, and that, in vitro , a large proportion of cells can be made to express TH. Experiments are currently in progress to tag these TH-expressing cells with the hTH-GFP transgene, purify them by FACS and transplant the cells into rat and monkey models Parkinson's disease. We will use PET scanning to evaluate the survival of engrafted cells as well as their ability to produce DA in vivo . Moreover, whether the graft provides functional recovery of motor deficits will be continually assessed using a battery of behavioral tests.

The ultimate goals of this research program are a fuller understanding of the cellular and molecular processes regulating the differentiation of DA traits in stem cells, and the application of that knowledge to transplantation strategies for the treatment of Parkinson's disease in humans.

Related publications:

Suon S, Jin H, Donaldson AE, Caterson EJ, Tuan RS, Deschennes G, Marshall C, and Iacovitti L . Adult human bone marrow stem cells transiently differentiate in culture to express CNS proteins. Stem Cells 2004. Submitted.

Yang M, Donaldson AE, Marshall CE, Shen J, Iacovitti L . Studies on the differentiation of dopaminergic traits in human neural progenitor cells in vitro and in vivo . Cell Transplantation 2004. In Press.

Yang M, Donaldson AE, Jiang Y, Iacovitti L. Factors influencing the differentiation of dopaminergic traits in transplanted neural stem cells. Mol Cell Neurobiol 2003 Oct;23(4-5):851-64.

Yang M, Stull ND, Snyder EY, Berk MA, Iacovitti L . Neuronal stem cells spontaneously differentiate into dopaminergic neurons after transplantation into the intact or 6-hydroxydopamine lesioned rate. Exp Neurol 2002;177:50-60.

Stull ND, Jung JW, Iacovitti L . Induction of a dopaminergic phenotype in cultured striatal neurons by bone morphogenetic proteins. B rain Res Dev Brain Res . 2001 Sep 23;130(1):91-8.

Iacovitti L , Stull ND, Jin H. Differentiation of human dopamine neurons from an embryonic carcinomal stem cell line. Brain Res . 2001 Aug 31;912(1):99-104.