The goal of this proposal is to directly derive patient-specific induced pluripotent stem cell (iPSC) lines from skin of patients with Multiple Sclerosis (MS) and Pakinson’s Disease (PD). A patient-specific iPSC line is a virtual clone of the patient because most cells of that patient can be differentiated from his/her iPSC in laboratory. Once they become available, those iPSC lines will allow scientists in any laboratory to obtain a large number of various types of cells from those MS and PD patients via in vitro differentiation. One obstacle for understanding disease mechanisms is the lack of in vitro systems to study the development of disease, especially for diseases of the human central nervous system (CNS) such as MS and PD. Animal models of the CNS diseases often fail to duplicate the true human diseases. Patient-specific iPSC generated by our proposal have the potential to provide all scientists unlimited access to diseased cells of individual patients.
We have constructed lentivirus that can introduce a stem cell selection marker into human skin cells with high efficiency and stability. We also successfully reprogrammed skin cells into iPSC in our laboratory. The high efficiency stem cell selection marker allows the selection of rare successfully reprogrammed cells. With access to one of the largest MS and PD patient populations in California, we are able to obtain skin biopsies from patients with various genetic background and pathological status. Acknowledging the value of MS iPSC and our expertise, the National MS Society has awarded us a grant to begin the work of establishing MS iPSC. Because non-NIH approved human embryonic stem cell (hESC) lines will be used in our cell fusion experiment, federal funding can not be used in our proposal.
With our MS society funded proposal as a starting point, we propose to generate a collection of disease-specific iPSC lines from MS and PD patients. We will first reprogram our MS skin cells into iPSC, which have a stem cell selection marker introduced by lentivirus. Second, PD iPSC lines will be generated with similar procedures. Finally, a collection of iPSC lines will be generated from patients with diverse genetic background and pathological status of MS and PD. Besides distributing those MS/PD iPSC to the research community, our proposal develops a protocol for large-scale systematic generation of patient-specific iPSC collections of various diseases, which impacts the whole stem cell field beyond MS and PD.
Statement of Benefit to California:
Approximately one of every thousand Californians suffers from multiple sclerosis (MS), which is the most common neural disorders without known cause, means of prevention, or cure. Parkinson’s Disease (PD) is the second common neurodegenerative disorder and affect one in 100 individuals over the age of 50. Here, we propose to derive induced pluripotent stem cell (iPSC) lines from skin of MS and PD patients. These cells can be used to identify genes and pathways that are involved in MS and PD as well as for drug discovery for treating MS and PD. These iPSC will directly benefit the large population of MS and PD patients in California. The protocol for generating disease-specific stem cell lines developed in this proposal will impact the whole field of stem cell research and application.