Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Encapsulating Bioactive Hydrogels Improve Rat Heart Function Post Myocardial Infarction.

Andre Chow,Richard J Jabbour,Daniel J Stuckey,Sian E Harding,Emaddin Kidher,Catherine A Mansfield,Ara Darzi,Molly M Stevens,Mark Rocco,Thanos Athanasiou

doi:10.1016/j.stemcr.2017.09.003

Abstract

SummaryTissue engineering offers an exciting possibility for cardiac repair post myocardial infarction. We assessed the effects of combined polyethylene glycol hydrogel (PEG), human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM), and erythropoietin (EPO) therapy in a rat model of myocardial infarction. PEG with/out iPSC-CMs and EPO; iPSC-CMs in saline; or saline alone was injected into infarcted hearts shortly after infarction. Injection of almost any combination of the therapeutics limited acute elevations in chamber volumes. After 10 weeks, attenuation of ventricular remodeling was identified in all groups that received PEG injections, while ejection fractions were significantly increased in the gel-EPO, cell, and gel-cell-EPO groups. In all treatment groups, infarct thickness was increased and regions of muscle were identified within the scar. However, no grafted cells were detected. Hence, iPSC-CM-encapsulating bioactive hydrogel therapy can improve cardiac function post myocardial infarction and increase infarct thickness and muscle content despite a lack of sustained donor-cell engraftment.

Highlights

Pharmacological and surgical treatments have improved prognosis post myocardial infarction (MI), but there is still no effective method to replace the lost tissue, meaning that heart failure remains a leading cause of mortality and morbidity worldwide (Roger et al, 2012).Regenerative medicine has the potential to repair damaged myocardium (Segers and Lee, 2008)
Many cells with regenerative potential have been proposed, including those derived from blood, bone marrow, adipose, and cardiac tissue (Segers and Lee, 2008). Each of these cell types has the ability to differentiate into new contractile cardiomyocytes, the efficiency of differentiation is low (Murry et al, 2006)
Embryonic stem cells (ESCs) and induced pluripotent stem cells have true cardiomyogenic potential (Zhang et al, 2009; Chong et al, 2014) and may offer a more effective cell type for cardiac regeneration. iPSCs can be expanded as highly purified and specific cell populations and avoid many of the immunological and ethical problems associated with ESCs (Yamanaka, 2009), making them suitable for clinical use (Chong et al, 2014)

Summary

Introduction

Pharmacological and surgical treatments have improved prognosis post myocardial infarction (MI), but there is still no effective method to replace the lost tissue, meaning that heart failure remains a leading cause of mortality and morbidity worldwide (Roger et al, 2012).Regenerative medicine has the potential to repair damaged myocardium (Segers and Lee, 2008). Many cells with regenerative potential have been proposed, including those derived from blood, bone marrow, adipose, and cardiac tissue (Segers and Lee, 2008). Each of these cell types has the ability to differentiate into new contractile cardiomyocytes, the efficiency of differentiation is low (Murry et al, 2006). Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have true cardiomyogenic potential (Zhang et al, 2009; Chong et al, 2014) and may offer a more effective cell type for cardiac regeneration. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have true cardiomyogenic potential (Zhang et al, 2009; Chong et al, 2014) and may offer a more effective cell type for cardiac regeneration. iPSCs can be expanded as highly purified and specific cell populations and avoid many of the immunological and ethical problems associated with ESCs (Yamanaka, 2009), making them suitable for clinical use (Chong et al, 2014)

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