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

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.

Antioxidant preconditioning improves therapeutic outcomes of adipose tissue-derived mesenchymal stem cells through enhancing intrahepatic engraftment efficiency in a mouse liver fibrosis model

“…Previous studies have suggested that antioxidant pretreatment could improve cell survival and enhance ADSC therapeutic effects for myocardial infarction [19,20]. In addition, it has also been suggested that antioxidant preconditioning could preserve stemness of mesenchymal stem cells [21, trypsin-EDTA (Gibco, USA) and passaged at a ratio of 1:3.…”

Evaluation of the potential of nanoparticles containing active substances in selected chronic diseases

“…Ma et al suggested the usage of melatonin, which is a powerful endogenous antioxidant, for protecting cells against oxidative stress. 44 In order to increase the effectiveness of this antioxidant, the authors developed a technique for melatonin encapsulation in PLGA-mPEG nanoparticles (Mel-NPs). They observed that Mel-NPs achieved a higher melatonin bioactivity index over time and a better therapeutic effect than a conventional melatonin preparation in the model of rat myocardial infarction.…”

“…They observed that Mel-NPs achieved a higher melatonin bioactivity index over time and a better therapeutic effect than a conventional melatonin preparation in the model of rat myocardial infarction. 44 Myocardial infarction therapy using PLGA NPs was also proposed by Nakano et al 45 who developed bioabsorbable irbesartan-loaded PLGA NPs. The efficacy of irbesartan-NPs was studied in the model of ischemia-reperfusion injury in the mouse heart, showing that such NPs may affect the limitation of infarct size.…”

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“…Unfortunately, the activity of these compounds can deteriorate under physiological conditions, thereby negating their therapeutic value. Now, researchers from the laboratory of Yundai Chen and Feng Cao (Chinese PLA General Hospital, Beijing, People's Republic of China) have developed a means of protecting melatonin and enhancing stem cell‐mediated cardiac repair . In their S tem C ells study, Dong et al discovered that encapsulation within a polymeric nanoparticle both protected melatonin from degradation and permitted controlled melatonin release.…”