Exosome lncRNA IFNG-AS1 derived from mesenchymal stem cells of human adipose ameliorates neurogenesis and ASD-like behavior in BTBR mice.

Autor: Fu Y; Research Center for Translational Medicine at East Hospital, School of Medicine, Tongji University, Shanghai, 200010, China., Zhang YL; Research Center for Translational Medicine at East Hospital, School of Medicine, Tongji University, Shanghai, 200010, China.; Department of Pathology, Air Force Medical Center, Beijing, 100142, China., Liu RQ; Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, 200010, China., Xu MM; Research Center for Translational Medicine at East Hospital, School of Medicine, Tongji University, Shanghai, 200010, China., Xie JL; Research Center for Translational Medicine at East Hospital, School of Medicine, Tongji University, Shanghai, 200010, China., Zhang XL; Research Center for Translational Medicine at East Hospital, School of Medicine, Tongji University, Shanghai, 200010, China., Xie GM; Research Center for Translational Medicine at East Hospital, School of Medicine, Tongji University, Shanghai, 200010, China., Han YT; Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, 200010, China., Zhang XM; Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, 200010, China., Zhang WT; Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, 200010, China., Zhang J; Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, 200010, China. 96755@tongji.edu.cn.; Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, 200092, China. 96755@tongji.edu.cn., Zhang J; Research Center for Translational Medicine at East Hospital, School of Medicine, Tongji University, Shanghai, 200010, China. 92870@tongji.edu.cn.; Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China. 92870@tongji.edu.cn.; Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, 200092, China. 92870@tongji.edu.cn.
Jazyk: angličtina
Zdroj: Journal of nanobiotechnology [J Nanobiotechnology] 2024 Feb 17; Vol. 22 (1), pp. 66. Date of Electronic Publication: 2024 Feb 17.
DOI: 10.1186/s12951-024-02338-2
Abstrakt: Background: The transplantation of exosomes derived from human adipose-derived mesenchymal stem cells (hADSCs) has emerged as a prospective cellular-free therapeutic intervention for the treatment of neurodevelopmental disorders (NDDs), as well as autism spectrum disorder (ASD). Nevertheless, the efficacy of hADSC exosome transplantation for ASD treatment remains to be verified, and the underlying mechanism of action remains unclear.
Results: The exosomal long non-coding RNAs (lncRNAs) from hADSC and human umbilical cord mesenchymal stem cells (hUCMSC) were sequenced and 13,915 and 729 lncRNAs were obtained, respectively. The lncRNAs present in hADSC-Exos encompass those found in hUCMSC-Exos and are associated with neurogenesis. The biodistribution of hADSC-Exos in mouse brain ventricles and organoids was tracked, and the cellular uptake of hADSC-Exos was evaluated both in vivo and in vitro. hADSC-Exos promote neurogenesis in brain organoid and ameliorate social deficits in ASD mouse model BTBR T + tf/J (BTBR). Fluorescence in situ hybridization (FISH) confirmed lncRNA Ifngas1 significantly increased in the prefrontal cortex (PFC) of adult mice after hADSC-Exos intraventricular injection. The lncRNA Ifngas1 can act as a molecular sponge for miR-21a-3p to play a regulatory role and promote neurogenesis through the miR-21a-3p/PI3K/AKT axis.
Conclusion: We demonstrated hADSC-Exos have the ability to confer neuroprotection through functional restoration, attenuation of neuroinflammation, inhibition of neuronal apoptosis, and promotion of neurogenesis both in vitro and in vivo. The hADSC-Exos-derived lncRNA IFNG-AS1 acts as a molecular sponge and facilitates neurogenesis via the miR-21a-3p/PI3K/AKT signaling pathway, thereby exerting a regulatory effect. Our findings suggest a potential therapeutic avenue for individuals with ASD.
(© 2024. The Author(s).)
Databáze: MEDLINE
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