Cografting astrocytes improves cell therapeutic outcomes in a Parkinson’s disease model

Jae Jin Song, Sang Min Oh, Oh Chan Kwon, Noviana Wulansari, Hyun Seob Lee, Mi Yoon Chang, Eunsoo Lee, Woong Sun, Sang Eun Lee, Sunghoe Chang, Heeyoung An, Changjoon Lee, Sang Hun Lee

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Abstract

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.

Original languageEnglish
Pages (from-to)463-482
Number of pages20
JournalJournal of Clinical Investigation
Volume128
Issue number1
DOIs
Publication statusPublished - 2018 Jan 2

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Song, J. J., Oh, S. M., Kwon, O. C., Wulansari, N., Lee, H. S., Chang, M. Y., Lee, E., Sun, W., Lee, S. E., Chang, S., An, H., Lee, C., & Lee, S. H. (2018). Cografting astrocytes improves cell therapeutic outcomes in a Parkinson’s disease model. Journal of Clinical Investigation, 128(1), 463-482. https://doi.org/10.1172/JCI93924