한빛사 논문
순천향대학교 서울병원
Yeo Min Yoon1, Jun Hee Lee1,2, Keon-Hyoung Song3, Hyunjin Noh4,5, Sang Hun Lee1,2,*
1 Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul 04401, Republic of Korea.
2 Departments of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 330-930, Republic of Korea.
3 Department of Pharmaceutical Engineering, College of Medical Science, Soonchunhyang University, Asan 31538, Republic of Korea
4 Department of Internal Medicine, Soonchunhyang University, Seoul 04401, Republic of Korea.
5 Hyonam Kidney Laboratory, Soonchunhyang University, Seoul 04401, Republic of Korea.
*Corresponding author: Sang Hun Lee, Ph.D. Soonchunhyang Medical Science Research Institute, Soonchunhyang University Seoul Hospital, 59, Daesagwan-ro (657 Hannam-dong), Yongsan-gu, Seoul 140-887, Republic of Korea.
Abstract
Chronic kidney disease (CKD) is caused by dysfunctional kidneys, which result in complications like cardiovascular diseases. CKD‐induced pathophysiological conditions decrease efficacy of autologous mesenchymal stem/stromal cell (MSC)‐based therapy by reducing MSC functionality. To enhance therapeutic potential in patients with CKD, we isolated exosomes derived from melatonin‐treated healthy MSCs (MT‐exosomes) and assessed the biological functions of MT‐exosome‐treated MSCs isolated from patients with CKD (CKD‐MSCs). Treatment with melatonin increased the expression of cellular prion protein (PrPC) in exosomes isolated from MSCs through the upregulation of miR‐4516. Treatment with MT‐exosomes protected mitochondrial function, cellular senescence, and proliferative potential of CKD‐MSCs. MT‐exosomes significantly increased the level of angiogenesis‐associated proteins in CKD‐MSCs. In a murine hindlimb ischemia model with CKD, MT‐exosome‐treated CKD‐MSCs improved functional recovery and vessel repair. These findings elucidate the regenerative potential of MT‐exosome‐treated CKD‐MSCs via the miR‐4516‐PrPC signaling axis. This study suggests that the treatment of CKD‐MSCs with MT‐exosomes might be a powerful strategy for developing autologous MSC‐based therapeutics for patients with CKD. Furthermore, miR‐4516 and PrPC could be key molecules for enhancing the regenerative potential of MSCs in ischemic diseases.
Keywords : cellular prion protein, chronic kidney diseases, exosome, ischemic disease, melatonin, mesenchymal , stem/stromal cells
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