Functional Improvement of Infarcted Heart by Co-Injection of Embryonic Stem Cells with Temperature-Responsive Chitosan Hydrogel

Abstract

Transplantation of embryonic stem cells (ESCs) can improve cardiac function in treatment of myocardial infarction. The low rate of cell retention and survival within the ischemic tissues makes the application of cell transplantation techniques difficult. In this study, we used a temperature-responsive chitosan hydrogel (as scaffold) combined with ESCs to maintain viable cells in the infarcted tissue. Temperature-responsive chitosan hydrogel was prepared and injected into the infarcted heart wall of rat infarction models alone or together with mouse ESCs. The result showed that the 24-h cell retention and 4 week graft size of both groups was significantly greater than with a phosphate buffered saline control. After 4 weeks of implantation, heart function, wall thickness, and microvessel densities within the infarct area improved in the chitosan + ESC, chitosan, and ESC group more than the PBS control. Of the three groups, the chitosan + ESC performed best. Results of this study indicate that temperature-responsive chitosan hydrogel is an injectable scaffold that can be used to deliver stem cells to infarcted myocardium. It can also increase cell retention and graft size. Cardiac function is well preserved, too.

A Conductive Polymer Hydrogel Supports Cell Electrical Signaling and Improves Cardiac Function After Implantation into Myocardial Infarct

“…18,19 After MI, cardiomyocyte death results in a noncontractile fibrotic scar and altered electric properties, including delayed impulse propagation across the scar region, which contributes to ventricular dysfunction. Because adult cardiomyocytes have a limited regenerative capability after an MI, 20 new treatment strategies are required to preserve ventricular function and prevent adverse remodeling. We and others have previously reported that matrix biopolymers (eg, fibrin glue, collagen, and hydrogels) have shown much promise in preserving cardiac function after an MI, providing structural support to prevent thinning and dilation of the infarct scar.…”

Injectable Acellular Hydrogels for Cardiac Repair

“…These gels exhibit a thermoresponsive gelation that is tuned to occur at 37°C by changing the glyoxal concentration, while hydrogel degradation is controlled by the degree of deacetylation [53,54]. In a rat infarct model, a thermally responsive chitosan was injected 1 week post-MI [28]. Four weeks after hydrogel injection, the myocardium thickness was significantly increased compared to PBS controls, even though the amount of chitosan present in the myocardium after 4 weeks had substantially decreased due to hydrogel degradation.…”

“…However, these approaches are limited by the invasive procedure in which they are applied, and clinical adoption has not occurred. In order to circumvent the invasive surgical placement of restraining devices early post-MI, our group and others have begun to explore the use of injectable materials, and specifically hydrogels, to limit infarct expansion and normalize the regional stress distribution [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35].…”

Current status of stem cell therapy: opportunities and limitations

“…Biomimetic scaffolds are made of natural or synthetic polymers or natural/synthetic hybrids. Natural polymers-collagen (Ott et al, 2008), fibrin (Christman et al, 2004), alginate (Landa et al, 2008), Matrigel (Giraud et al, 2008), chitosan (Lu et al, 2009), and hyaluronic acid (Holloway et al, 2015) are biodegradable proteins or polysaccharides that have a structure similar to the native components of the extracellular matrix, making them biocompatible and less immunogenic than synthetic polymers. They also have a higher capacity for cell adhesion and influence on various cellular functions.…”