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Lin28B regulates the fate of grafted mesenchymal stem cells and enhances their protective effects against Alzheimer's disease by upregulating IGF‐2
Author(s) -
Wu Kaimin,
Zhang Ruiyi,
Lu Yanhui,
Wen Lulu,
Li Yanfei,
Duan Ranran,
Yao Yaobing,
Jia Yanjie
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28750
Subject(s) - mesenchymal stem cell , bioluminescence imaging , microbiology and biotechnology , downregulation and upregulation , transplantation , cancer research , cell growth , microglia , cell , neuroprotection , transfection , stem cell , biology , chemistry , immunology , neuroscience , medicine , cell culture , inflammation , biochemistry , luciferase , genetics , gene
Mesenchymal stem cells (MSCs) transplantation has emerged as a potential therapeutic approach for Alzheimer's disease (AD). However, the poor proliferation capacity and low survival rate of engrafted MSCs in the hostile microenvironment of AD limit their therapeutic efficiency. Lin28B is a conserved RNA‐binding protein associated with cell self‐renewal and survival. The purpose of the present study was to explore whether lin28B might influence the functions of implanted MSCs and strengthen their neuroprotective potential in AD. A gain‐of‐function assay was used to upregulate lin28B expression in MSCs by lentiviral transfection. Our in vitro results indicated that lin28B promoted MSCs proliferation and migration, and protected MSCs against Aβ1–42‐induced cell death by upregulating insulin‐like growth factor‐2 (IGF‐2). Blockage of IGF‐2 partially abrogated the above effects of lin28B. After intracerebroventricular injection into amyloid precursor protein/presenilin 1 mice, implanted MSCs were monitored using bioluminescence imaging. We observed that administration of MSCs transfected with lin28B significantly stimulated their proliferation and prolonged cell retention after delivery. Moreover, administration of the transfected MSCs markedly mitigated cognitive deficits, promoted amyloid plaque clearance, decreased the activation of microglia, and reduced neuronal cell death. The data above confirmed our hypothesis that lin28B is a crucial modulator determining the fate of transplanted MSCs by regulating IGF‐2‐associated pathways and thereby enhancing their protective effects against AD.