NDLI: Rebuilding hippocampus neural circuit with hADSC-derived neuron cells for treating ischemic stroke

Content Provider	Springer Nature : BioMed Central
Author	Wang, Jian Hao, Rui Jiang, Tianfang Guo, Xuanxuan Zhou, Fei Cao, Limei Gao, Fengjuan Wang, Guangming Wang, Juan Ning, Ke Zhong, Chunlong Chen, Xu Huang, Ying Xu, Jun Gao, Shane
Abstract	Background Human adipose-derived stem cells (hADSCs) have been demonstrated to be a promising autologous stem cell source for treating various neuronal diseases. Our study indicated that hADSCs could be induced into neuron-like cells in a stepwise manner that are characterized by the positive expression of MAP2, SYNAPSIN 1/2, NF-200, and vGLUT and electrophysiological activity. We first primed hADSCs into neuron-like cells (hADSC-NCs) and then intracerebrally transplanted them into MCAO reperfusion mice to further explore their in vivo survival, migration, integration, fate commitment and involvement in neural circuit rebuilding. Results The hADSC-NCs survived well and transformed into MAP2-positive, Iba1- or GFAP-negative cells in vivo while maintaining some proliferative ability, indicated by positive Ki67 staining after 4 weeks. hADSC-NCs could migrate to multiple brain regions, including the cortex, hippocampus, striatum, and hypothalamus, and further differentiate into mature neurons, as confirmed by action potential elicitation and postsynaptic currents. With the aid of a cell suicide system, hADSC-NCs were proven to have functionally integrated into the hippocampal memory circuit, where they contributed to spatial learning and memory rescue, as indicated by LTP improvement and subsequent GCV-induced relapse. In addition to infarction size shrinkage and movement improvement, MCAO-reperfused mice showed bidirectional immune modulation, including inhibition of the local proinflammatory factors IL-1α, IL-1β, IL-2, MIP-1β and promotion proinflammatory IP-10, MCP-1, and enhancement of the anti-inflammatory factors IL-15. Conclusion Overall, hADSC-NCs used as an intermediate autologous cell source for treating stroke can rebuild hippocampus neuronal circuits through cell replacement.
Related Links	https://cellandbioscience.biomedcentral.com/counter/pdf/10.1186/s13578-022-00774-x.pdf
Ending Page	18
Page Count	18
Starting Page	1
File Format	HTM / HTML
ISSN	20453701
DOI	10.1186/s13578-022-00774-x
Journal	Cell & Bioscience
Issue Number	1
Volume Number	12
Language	English
Publisher	BioMed Central
Publisher Date	2022-04-04
Access Restriction	Open
Subject Keyword	Cell Biology Microbiology Stem Cells Neurobiology Proteomics Adipose-derived stem cells (ADSCs) hADSC-derived neuron-like cells (hADSC-NCs) Middle cerebral artery occlusion (MCAO) National Institute of Health Stroke Scale (NIHSS) Rogers scale system
Content Type	Text
Resource Type	Article
Subject	Biochemistry, Genetics and Molecular Biology
Journal Impact Factor	6.1/2023
5-Year Journal Impact Factor	7/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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