Cografting astrocytes improves cell therapeutic outcomes in a Parkinson’s disease model
| Autor: | Hyun Seob Lee, Jae Jin Song, Sang Hun Lee, Noviana Wulansari, Mi Yoon Chang, Sunghoe Chang, Sangeun Lee, Oh Chan Kwon, Woong Sun, Eunsoo Lee, Heeyoung An, Sang Min Oh, C. Justin Lee |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Parkinson's disease Neuroprotection Rats Sprague-Dawley Mice 03 medical and health sciences Therapeutic approach 0302 clinical medicine Neural Stem Cells Mesencephalon Nuclear Receptor Subfamily 4 Group A Member 2 Animals Medicine Parkinson Disease Secondary Microglia biology business.industry General Medicine medicine.disease Neural stem cell Rats Transplantation Disease Models Animal 030104 developmental biology medicine.anatomical_structure Astrocytes Hepatocyte Nuclear Factor 3-beta Commentary biology.protein Neuron business Neuroscience 030217 neurology & neurosurgery Neurotrophin |
| Zdroj: | Journal of Clinical Investigation. 128:463-482 |
| ISSN: | 1558-8238 0021-9738 |
| Popis: | Transplantation of neural progenitor cells (NPCs) is a potential therapy for treating neurodegenerative disorders, but this approach has faced many challenges and limited success, primarily because of inhospitable host brain environments that interfere with enriched neuron engraftment and function. Astrocytes play neurotrophic roles in the developing and adult brain, making them potential candidates for helping with modification of hostile brain environments. In this study, we examined whether astrocytic function could be utilized to overcome the current limitations of cell-based therapies in a murine model of Parkinson's disease (PD) that is characterized by dopamine (DA) neuron degeneration in the midbrain. We show here that cografting astrocytes, especially those derived from the midbrain, remarkably enhanced NPC-based cell therapeutic outcomes along with robust DA neuron engraftment in PD rats for at least 6 months after transplantation. We further show that engineering of donor astrocytes with Nurr1 and Foxa2, transcription factors that were recently reported to polarize harmful immunogenic glia into the neuroprotective form, further promoted the neurotrophic actions of grafted astrocytes in the cell therapeutic approach. Collectively, these findings suggest that cografting astrocytes could be a potential strategy for successful cell therapeutic outcomes in neurodegenerative disorders. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|