Myocardial infarction (MI) affects more than 8 million people in the United States. MI causes extensive death of heart cells and partial loss of heart function. Stem cell therapy has been considered as a potential approach to regenerate lost heart tissue and restore heart function. However, current stem cell therapy has an extremely low efficacy. Various studies have shown that most of the injected cells died few weeks after injection, and few of the surviving cells differentiated into cardiac cells for regeneration. Such low efficacy significantly limits the application of stem cell therapy in clinics.
Hypoxia in infarcted hearts has been identified as one of the major causes. Many approaches have been used to address the cell survival issue under hypoxic condition, such as transfecting cells with pro-survival gene Akt and hyperbaric oxygenation of cells. However, these approaches may generate new concerns. Gene transfection by virus brings up safety concerns, while hyperbaric oxygenation may generate reactive oxygen species that damage cells. In addition, hyperbaric oxygenation may not allow cells to survive under hypoxic condition for a couple of weeks, a period usually needed for the establishment of angiogenesis.
To overcome current limits, Dr. Jianjun Guan’s group in Department of Materials Science and Engineering at The Ohio State University created a novel oxygen-releasing system capable of sustainedly supplying oxygen to stem cells. The oxygen-releasing system consisted of hydrogen peroxide (H2O2)-releasing microspheres, catalase, and an injectable, thermosensitive hydrogel. The microspheres were based on degradable poly(lactide-co-glycolide) (PLGA), and a complex of H2O2 and poly(2-vinlypyrridione) (PVP). The oxygen was generated after the H2O2 released from microspheres was decomposed by catalase. The hydrogel was designed to improve the retention of microspheres and stem cells in the beating heart during myocardial injection. The oxygen-releasing system was capable of sustainedly releasing oxygen for at least two weeks. Under hypoxic condition mimicking that of the infarcted hearts, cardiac progenitor cells experienced massive cell death. Introduction of oxygen release significantly augmented cell survival; no cell death was found after seven days of culture, and cells even grew after seven days. Under hypoxic condition, cardiac differentiation of cardiac progenitor cells was completely silenced. However, introduction of oxygen release restored the differentiation. These results demonstrate that the developed oxygen-releasing system has great potential to improve the efficacy of cardiac stem cell therapy.