Presentation Title

Investigating the Migrational Capacity of Genetically Engineered Cells in a Model of Parkinson’s Disease

Faculty Mentor

Kerry Thompson

Start Date

23-11-2019 10:45 AM

End Date

23-11-2019 11:30 AM

Location

88

Session

poster 4

Type of Presentation

Poster

Subject Area

biological_agricultural_sciences

Abstract

The overall objective of this study is to investigate an alternative treatment for patients with Parkinson’s disease. In order to replace the damaged or lost dopamine-producing neurons, caused by the disease process, we genetically engineered immortalized rat mesencephalic cells with green fluorescent protein (GFP) and dopamine-synthesizing enzymes. Cells were characterized biochemically and then transplanted into an animal model of Parkinson’s disease. The present study examines whether a “stem cell-like” line engineered to produce GFP, has the capacity to integrate into the host brain, survive, differentiate, and remain at the transplant site. We investigated the migrational capacity of an immortal rat central nervous system progenitor cell line by examining serial sections throughout the cerebrum one week (N=2) and one month (N=2) after transplantation into the lesioned striatum of hemiparkinsonian, dyskinetic, rats. GFP-expressing cells were pre-labeled with the nuclear marker hoechst. We observed and recorded behavioral effects before transplantation, one week post-transplantation, and one month post transplantation for the remaining animals. Histological examination was then carried out one week and one month post-transplantation using endogenous fluorescence and immunohistochemical analysis. These studies will determine if these transplanted neurons remain viable at the transplant site without migration or fusion as seen in our previous studies. The initial results suggest that the AF5 cell line does not migrate or fuse, while the longer-term effects are still being analyzed. Future studies will include transplantation of the same parental cell line engineered to produce dopamine (AF5THDDC) into the hemiparkinsonian, dyskinetic, rat model. These data will be important to understand the potential for using genetic engineering and transplantation of neurons as an alternative cell-based approach to intractable diseases of the central nervous system.

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Nov 23rd, 10:45 AM Nov 23rd, 11:30 AM

Investigating the Migrational Capacity of Genetically Engineered Cells in a Model of Parkinson’s Disease

88

The overall objective of this study is to investigate an alternative treatment for patients with Parkinson’s disease. In order to replace the damaged or lost dopamine-producing neurons, caused by the disease process, we genetically engineered immortalized rat mesencephalic cells with green fluorescent protein (GFP) and dopamine-synthesizing enzymes. Cells were characterized biochemically and then transplanted into an animal model of Parkinson’s disease. The present study examines whether a “stem cell-like” line engineered to produce GFP, has the capacity to integrate into the host brain, survive, differentiate, and remain at the transplant site. We investigated the migrational capacity of an immortal rat central nervous system progenitor cell line by examining serial sections throughout the cerebrum one week (N=2) and one month (N=2) after transplantation into the lesioned striatum of hemiparkinsonian, dyskinetic, rats. GFP-expressing cells were pre-labeled with the nuclear marker hoechst. We observed and recorded behavioral effects before transplantation, one week post-transplantation, and one month post transplantation for the remaining animals. Histological examination was then carried out one week and one month post-transplantation using endogenous fluorescence and immunohistochemical analysis. These studies will determine if these transplanted neurons remain viable at the transplant site without migration or fusion as seen in our previous studies. The initial results suggest that the AF5 cell line does not migrate or fuse, while the longer-term effects are still being analyzed. Future studies will include transplantation of the same parental cell line engineered to produce dopamine (AF5THDDC) into the hemiparkinsonian, dyskinetic, rat model. These data will be important to understand the potential for using genetic engineering and transplantation of neurons as an alternative cell-based approach to intractable diseases of the central nervous system.