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Stem Cells. 2018 Apr;36(4):540-550. doi: 10.1002/stem.2777. Epub 2018 Feb 1.

Poly(Lactide-Co-Glycolide)-Monomethoxy-Poly-(Polyethylene Glycol) Nanoparticles Loaded with Melatonin Protect Adipose-Derived Stem Cells Transplanted in Infarcted Heart Tissue.

Author information

1
Department of Cardiology, Chinese PLA General Hospital, Beijing, People's Republic of China.
2
Laboratory of Controllable Nanopharmaceuticals, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, People's Republic of China.

Abstract

Stem cell transplantation is a promising therapeutic strategy for myocardial infarction. However, transplanted cells face low survival rates due to oxidative stress and the inflammatory microenvironment in ischemic heart tissue. Melatonin has been used as a powerful endogenous antioxidant to protect cells from oxidative injury. However, melatonin cannot play a long-lasting effect against the hostile microenvironment. Nano drug delivery carriers have the ability to protect the loaded drug from degradation in physiological environments in a controlled manner, which results in longer effects and decreased side effects. Therefore, we constructed poly(lactide-co-glycolide)-monomethoxy-poly-(polyethylene glycol) (PLGA-mPEG) nanoparticles to encapsulate melatonin. We tested whether the protective effect of melatonin encapsulated by PLGA-mPEG nanoparticles (melatonin nanoparticles [Mel-NPs]) on adipose-derived mesenchymal stem cells (ADSCs) was enhanced compared to that of free melatonin both in vitro and in vivo. In the in vitro study, we found that Mel-NPs reduced formation of the p53- cyclophilin D complex, prevented mitochondrial permeability transition pores from opening, and rescued ADSCs from hypoxia/reoxygenation injury. Moreover, Mel-NPs can achieve higher ADSC survival rates than free melatonin in rat myocardial infarction areas, and the therapeutic effects of ADSCs pretreated with Mel-NPs were more apparent. Hence, the combination of Mel-NPs and stem cell transplantation may be a promising strategy for myocardial infarction therapy. Stem Cells 2018;36:540-550.

KEYWORDS:

Melatonin; Myocardial infarction; Nanoparticles; Poly(lactide-co-glycolide)-monomethoxy-poly-(polyethylene glycol); Stem cell transplantation

PMID:
29327399
DOI:
10.1002/stem.2777
[Indexed for MEDLINE]
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