Direct Neural Conversion of Adult Human Fibroblasts: Generation and Transplantation of Dopaminergic Neurons for Cell-Based Replacement Therapy
| Main Authors: | Shelby Shrigley, Janelle Drouin-Ouellet, Maria Pereira, Deirdre B Hoban, Tiago Cardoso, Malin Parmar |
|---|---|
| Format: | Proceeding poster eJournal |
| Bahasa: | eng |
| Terbitan: |
, 2017
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| Online Access: |
https://zenodo.org/record/2542058 |
Daftar Isi:
- Cell-based replacement therapy has great potential to improve the clinical outcome of Parkinson’s disease (PD). Induced neurons are a unique resource negating safety concerns associated with pluripotency, as well as ethical concerns with embryonic derived cells, whilst allowing for patient specific cells or matched donors. We have previously shown that dopaminergic (DA) neuronal fate could be generated from fetal fibroblasts using forced expression of Ascl1 and specific DA fate determinants, however this early protocol showed low efficiency when converting adult fibroblasts. Here we build on our reprogramming method to convert adult fibroblasts into induced dopaminergic neurons (iDANs) with a new combination of transcription factors combined with a REST knock-down. Generated iDANS show the presence of genes normally expressed in DA neurons including TH, NURR1 and PITX3. We are now investigating survival of iDANs following transplantation using different time points post-transduction in a rodent model of PD. Results provide a more robust and efficient protocol for the generation of iDANs and will help to pave the way for future research assessing their potential for brain repair.