Melatonin‐stimulated exosomes enhance the regenerative potential of chronic kidney disease‐derived mesenchymal stem/stromal cells via cellular prion proteins

Jan 29, 2020Journal of pineal research

Melatonin-activated cell packages improve healing ability of stem cells from chronic kidney disease through prion proteins

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Regenerative Health on OpenScience ↗PubMed ↗DOI ↗

Abstract

Treatment with melatonin-derived exosomes significantly improved the function of kidney stem cells from patients with chronic kidney disease.

Melatonin treatment increased the expression of cellular prion protein in exosomes from healthy stem cells.
Melatonin-derived exosomes protected against mitochondrial dysfunction, cellular aging, and loss of growth ability in kidney stem cells from patients with chronic kidney disease.
These exosomes also boosted levels of proteins related to blood vessel formation in the kidney stem cells.
In a mouse model of blood flow obstruction, kidney stem cells treated with melatonin-derived exosomes enhanced recovery and blood vessel repair.
The findings suggest that the signaling pathway involving miR-4516 and prion protein may play a role in improving the regenerative capacity of these kidney stem cells.

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Chronic kidney disease (CKD) is caused by dysfunctional kidneys, which result in complications like cardiovascular diseases. Chronic kidney disease-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 (PrP) 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-PrPsignaling 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 PrPcould be key molecules for enhancing the regenerative potential of MSCs in ischemic diseases. C C C

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Melatonin‐stimulated exosomes enhance the regenerative potential of chronic kidney disease‐derived mesenchymal stem/stromal cells via cellular prion proteins

Abstract

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