Transplantation strategies using CNS stem cells offer tremendous potential for replacing neuronal circuitry lost to Parkinson?s disease and other neurological disorders. The ability of CNS grafts to survive after transplant is crucial if therapeutic benefit is to be provided to a large number of patients with PD. Additionally, there must be an adequate source of donor cells. The purpose of this proposal is to insert the human telomerase gene (hTERT) into human postmortem-derived neural progenitor cells (HPCPs) in order to improve the survival of transplanted cells and ultimately increase the proliferation of desired cell types. HPCPs provide an easily accessible donor source, and ectopic expression of hTERT is a logical means by which to immortalize these cells in culture and decrease their susceptibility to apoptotic death following transplantation. Determining the effect of ectopic telomerase expression in HPCPs on population doublings, resistance to apoptosis and ability to differentiate into all CNS cell types is the crucial first step in investigating these methods. Assessing the viability, proliferation and differential fates of hTERT+ HPCPs transplanted to a 6-OHDA lesioned rat model of Parkinson?s disease, and evaluating functional recovery in transplant recipients will further characterize the extent to which these approaches may contribute to future stem cell therapy for neurological disorders. For the treatment of Parkinson? disease, a future step may include combining these methods with strategies likely to induce a dopaminergic fate among a subset of these progenitors.
| Richardson, R Mark; Nguyen, Binh; Holt, Shawn E et al. (2007) Ectopic telomerase expression inhibits neuronal differentiation of NT2 neural progenitor cells. Neurosci Lett 421:168-72 |
| Richardson, R M; Holloway, K L; Bullock, M R et al. (2006) Isolation of neuronal progenitor cells from the adult human neocortex. Acta Neurochir (Wien) 148:773-7 |
| Richardson, R Mark; Broaddus, William C; Holloway, Kathryn L et al. (2005) Grafts of adult subependymal zone neuronal progenitor cells rescue hemiparkinsonian behavioral decline. Brain Res 1032:11-22 |
| Richardson, R Mark; Broaddus, William C; Holloway, Kathryn L et al. (2005) Heterotypic neuronal differentiation of adult subependymal zone neuronal progenitor cells transplanted to the adult hippocampus. Mol Cell Neurosci 28:674-82 |
| Richardson, R Mark; Fillmore, Helen L; Holloway, Kathryn L et al. (2004) Progress in cerebral transplantation of expanded neuronal stem cells. J Neurosurg 100:659-71 |
