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Adipose Stem Cell-mediated Cardiac Repair: Melatonin Encapsulation to the Rescue!

Review of “Poly(Lactide-Co-Glycolide)-Monomethoxy-Poly-(Polyethylene Glycol) Nanoparticles Loaded with Melatonin Protect Adipose-Derived Stem Cells Transplanted in Infarcted Heart Tissue” from STEM CELLS by Stuart P. Atkinson

Adult stem cell therapy represents a promising means to treat heart failure, currently one of the most common causes of death worldwide, with therapeutic benefit deriving from the cocktail of secreted paracrine-acting factors that activate endogenous cardiac repair pathways. However, a recent systematic review reported only modest improvements in current adult stem cell therapies for heart failure [1], suggesting the need to further optimize current approaches to foster enhanced cardiac repair. One potential means to augment the therapeutic capacity of adult stem cells is to increase their survival chances in the inhospitable environment encountered at sites of tissues damage [2]. 

Now, a STEM CELLS study from the laboratory of Yundai Chen and Feng Cao (Chinese PLA General Hospital, Beijing, PR China) now describes how cotransplantation of nanoencapsulated melatonin [3, 4] can boost the survival and therapeutic effect of adipose-derived mesenchymal stem cells (ASCs) following injection into damaged rat cardiac tissue [5]. The authors hope that this new approach represents a practical means to inhibit the degradation of stem cell-protective compounds such as melatonin [6], enhance stem cell survival post-transplantation, and improve adult stem cell-mediated cardiac repair.

Ma et al. began by capturing melatonin in spherical, homogenous, and stable polymeric nanoparticles (Mel-NPs) composed of poly(lactide-co-glycolide)-monomethoxy-poly-(polyethylene glycol) (PLGA-mPEG [7]) to inhibit degradation and promote controlled drug release in sites of tissue damage. In vitro studies confirmed that Mel-NPs passed into ASCs via endocytosis and distributed themselves around the nucleus in the cytosol. Mechanistically, the authors discovered that Mel-NPs improved the secretion of crucial paracrine factors, lowered levels of cellular necrosis and apoptosis, and, overall, promoted the rescue of ASCs from hypoxia/reoxygenation injury.

Moving in vivo, when compared to cotransplantation with the “free” form of melatonin, Mel-NPs increased ASC survival following transplanted into damaged rat cardiac tissue during the acute phase of heart infarction. Encouragingly, this increase in ASC permanence in the heart led to an enhanced therapeutic effect, as evidenced by echocardiographic measurements of left ventricular ejection fraction (LVEF) 4 weeks after transplantation.

Overall, nanoencapsulation of melatonin appears to support the presence of therapeutically functional ASCs in the inhospitable environment of damaged cardiac tissues, thereby providing significant recovery of rat heart function. However, can nanoencapsulation come to the rescue of adult stem cell therapies for heart failure and other diseases and disorders in human patients? Stay tuned to the Stem Cells Portal to find out!


  1. Nguyen PK, Rhee J, and Wu JC, Adult stem cell therapy and heart failure, 2000 to 2016: A systematic review. JAMA Cardiology 2016;1:831-841.
  2. Shafiq M, Jung Y, and Kim SH, Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair. Biomaterials 2016;90:85-115.
  3. Sabzichi M, Samadi N, Mohammadian J, et al., Sustained release of melatonin: A novel approach in elevating efficacy of tamoxifen in breast cancer treatment. Colloids and Surfaces B: Biointerfaces 2016;145:64-71.
  4. Dun-xian T, Russel JR, Lucien CM, et al., Chemical and Physical Properties and Potential Mechanisms: Melatonin as a Broad Spectrum Antioxidant and Free Radical Scavenger. Current Topics in Medicinal Chemistry 2002;2:181-197.
  5. Ma Q, Yang J, Huang X, et al., Poly(Lactide‐Co‐Glycolide)‐Monomethoxy‐Poly‐(Polyethylene Glycol) Nanoparticles Loaded with Melatonin Protect Adipose‐Derived Stem Cells Transplanted in Infarcted Heart Tissue. STEM CELLS 2018;36:540-550.
  6. Harpsoe NG, Andersen LP, Gogenur I, et al., Clinical pharmacokinetics of melatonin: a systematic review. Eur J Clin Pharmacol 2015;71:901-9.
  7. Avgoustakis K, Beletsi A, Panagi Z, et al., PLGA-mPEG nanoparticles of cisplatin: in vitro nanoparticle degradation, in vitro drug release and in vivo drug residence in blood properties. J Control Release 2002;79:123-35.