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| Status |
Public on Oct 05, 2022 |
| Title |
Regeneration of the cerebral cortex by direct chemical reprogramming of macrophages into neuronal cells in acute ischemic stroke |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Ischemic stroke causes extensive neuronal cell death. Antithrombotic agents and rehabilitation are the primary treatment options but have limited efficacy. Therefore, to achieve radical neurological improvement, practical neuroregenerative technologies must be developed. Recently, direct chemical reprogramming using small molecules to transdifferentiate somatic cells into neurons has garnered much attention. We investigated the possibility of applying this technology for the treatment of ischemic stroke. During the acute phase of ischemic stroke, circulating monocytes increase chemotaxis and accumulate in the infarct area through the disrupted blood-brain barrier, where they differentiate into macrophages involved in inflammation and remodeling. Direct reprogramming of these monocyte-derived macrophages into neuronal cells in vivo is theoretically possible with the administration of small-molecule drugs. However, the efficacy of this neuroregenerative therapy cannot be verified because the optimal chemical compounds that convert macrophages into neurons have not yet been identified.
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| Overall design |
Direct chemical reprogramming of infiltrated monocyte-derived macrophages into neurons in the infarct area is theoretically a promising regenerative therapy for ischemic stroke. However, the optimal combination of small molecules to transdifferentiate macrophages into neurons has not yet been discovered. Here, we identified the essential small molecules and demonstrated that their administration generates a new neuronal layer in the infarct cortex by converting macrophages into neuronal cells, ultimately improving neurological function.
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| Contributor(s) |
Ninomiya I, Koyama A, Otsu Y, Kanazawa M, Onodera O |
| Citation missing |
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| Submission date |
Oct 02, 2022 |
| Last update date |
Oct 08, 2022 |
| Contact name |
Itaru Ninomiya |
| E-mail(s) |
ininomiya@bri.niigata-u.ac.jp
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| Organization name |
Brain Research Institute, Niigata University
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| Department |
Neurology
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| Street address |
1-757 Asahimachi-dori, Chuoku
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| City |
Niigata |
| State/province |
Niigata |
| ZIP/Postal code |
951-8585 |
| Country |
Japan |
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| Platforms (1) |
| GPL23159 |
[Clariom_S_Human] Affymetrix Clariom S Assay, Human (Includes Pico Assay) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA886450 |
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