Study on the therapeutic potential of induced neural stem cells for Alzheimer's disease in mice.

Autor: Ji Q; Department of Medical Imaging, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China., Lv Y; Department of Orthopedic Surgery, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou, China., Hu B; Fuzhou Medical College of Nanchang University, Fuzhou, 344099, Jiangxi, China., Su Y; Department of Respiratory and Critical Care Medicine, School of Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, 200433, China. ysu03@qub.ac.uk., Shaikh II; Central Laboratory of The Lishui Hospital of Wenzhou Medical University, Lishui People's Hospital, The First Affiliated Hospital of Lishui University, Lishui, 323000, Zhejiang, China. drorthospine@outlook.com., Zhu X; Department of Orthopedics, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China. zhuxu1632093@163.com.
Jazyk: angličtina
Zdroj: Biological research [Biol Res] 2024 Nov 24; Vol. 57 (1), pp. 89. Date of Electronic Publication: 2024 Nov 24.
DOI: 10.1186/s40659-024-00568-0
Abstrakt: Induced neural stem cells (iNSCs), which have similar properties to neural stem cells and are able to self-proliferate and differentiate into neural cell lineages, are expected to be potential cells for the treatment of neurodegeneration disease. However, cell therapy based on iNSCs transplantation is limited by the inability to acquire sufficient quantities of iNSCs. Previous studies have found that mouse and human fibroblasts can be directly reprogrammed into iNSCs with a single factor, Sox2. Here, we induced mouse embryonic fibroblasts (MEFs) into iNSCs by combining valproic acid (VPA) with the induction factor Sox2, and the results showed that VPA significantly improved the conversion efficiency of fibroblasts to iNSCs. The iNSCs exhibited typical neurosphere-like structures that can express NSCs markers, such as Sox2, Nestin, Sox1, and Zbtb16, and could differentiate into neurons, astrocytes, and oligodendrocytes in vitro. Subsequently, the iNSCs were stereotactically transplanted into the hippocampus of APP/PS1 double transgenic mice (AD mice). Post-transplantation, the iNSCs showed long-term survival, migrated over long distances, and differentiated into multiple types of functional neurons and glial cells in vivo. Importantly, the cognitive abilities of APP/PS1 mice transplanted with iNSCs exhibited significant functional recovery. These findings suggest that VPA enhances the conversion efficiency of fibroblasts into iNSCs when used in combination with Sox2, and iNSCs hold promise as a potential donor material for transplantation therapy in Alzheimer's disease.
Competing Interests: Declarations. Ethics approval and consent to participate: Animal experiments were conducted in accordance with the Shanghai Ethics Committee, and all procedures followed the guidelines of the Chinese Animal Welfare Agency. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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