Neuroprotective Effect of exosomes from adipose-derived stem cells in vitro Huntington's disease model through activating mitochondrial function
Wooseok Im1, Mijung Lee1, Tian Liu2, and Manho Kim1,3 1Department of Neurology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, 110744 Seoul, Korea 2Department of Molecular Medicine, USF Health Byrd Institute, Tampa, FL, USA 3Protein Metabolism Medical Research Center, College of Medicine, Seoul National University, Seoul, Korea Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by the aggregation of mutant Huntingtin (mHtt) and the accumulation of mHtt evokes mitochondrial dysfunction. Human adipose-derived stem cells (hASCs) have a potential for use in the treatment of incurable disorders, including HD. hASCs secrete various neurotrophic factors and microvesicles, and modulate hostile microenvironments affected by disease through paracrine mechanisms. Exosomes are small vesicles that transport nucleic acid and protein between cells. Here, we investigated the therapeutic role of exosomes from hASCs (ASC-exo) using in vitro HD model by examining pathological phenotypes of this model. Immunocytochemistry result showed that ASC-exo significantly decreases mHtt aggregates in R6/2 mice-derived neuronal cells. Western blot result further confirmed the reduction in mHtt aggregates level by ASC-exo treatment. ASC-exo treatment significantly increased expression of p-Akt, p-CREB, and PGC-1¥á in vitro HD model. In addition, MitoSOX Red, JC-1 and cell viability assay showed that ASC-exo reduces mitochondrial dysfunction and cell apoptosis of in vitro HD model. Our results indicated that ASC-exo reduced apoptotic cell death and recovered mHtt-induced mitochondrial dysfunction. These findings suggest that ASC-exo has a therapeutic potential for treating HD by modulating representative cellular phenotypes of HD.
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