Objective/Rationale:
Cell replacement remains one of the most promising approaches to treat Parkinson’s, particularly at late stages of the disease. Legal, ethical and pragmatic concerns have become major stumbling blocks in the development of human embryonic stem cells for this purpose. Therefore, the search for adult sources of cells remains a high priority. The recent establishment of human stem cell lines from amniotic fluid (AFS) collected during routine amniocenteses was consequently of great interest. Our goal in this proposal is to characterize the potential of AFS cells to
develop into dopamine neurons for use in PD.
Project Description:
Our overall objectives are the characterization of AFS cells to differentiate into dopamine (DA) neurons and the discovery of conditions which promote that process in culture. To accomplish this, cells will be grown with a variety of DA-inducing factors and/or be genetically engineered to express certain DA-specific genes after which their ability to develop into fully differentiated DA neurons will be assessed. Our hope is that these studies lay the foundation for future transplantation studies of AFS cells in animal models of PD.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
AFS cells could provide an abundant and practical source of human stem cells, free of ethical dilemma, that are non-tumor-forming and can be banked for autologous or allogeneic compatibility as replacement tissue in PD.
Anticipated Outcome:
We anticipate that at the completion of these studies, we will have determined 1) whether AFS cells express critical DA fate genes or can be induced to do so in culture and 2) whether these cells can differentiate fully into mature DA neurons. Additionally, it will be possible to compare the in vitro differentiation of AFS cells to other stem cell sources, such as human embryonic or adult bone marrow stem cells, with which we have had much experience in the past. These studies should serve as a first step towards evaluating the possible utility of AFS cells in cell replacement for PD. If, as we hope, AFS cells can differentiate into DA neurons in vitro, then we will be well-positioned in the future to proceed with transplantation studies in animal models of PD.
Final Outcome
Despite a detailed evaluation, Dr. Iacovitti was unable to replicate previous studies that demonstrated the ability to differentiate human amniotic fluid stem cells into dopamine-producing cells.