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Evaluation of Hydrogels Presenting Extracellular Matrix-Derived Adhesion Peptides and Encapsulating Cardiac Progenitor Cells for Cardiac Repair.

ABSTRACT: Cell therapy is an emerging paradigm for the treatment of heart disease. In spite of the exciting and promising preclinical results, the benefits of cell therapy for cardiac repair in patients have been modest at best. Biomaterials-based approaches may overcome the barriers of poor differentiation and retention of transplanted cells. In this study, we prepared and tested hydrogels presenting extracellular matrix (ECM)-derived adhesion peptides as delivery vehicles for c-kit+ cardiac progenitor cells (CPCs). We assessed their effects on cell behavior in vitro as well as cardiac repair in rats undergoing ischemia reperfusion. Hydrogels presenting the collagen-derived GFOGER peptide induced cardiomyocyte differentiation of CPCs as demonstrated by increased expression of cardiomyocyte structural proteins. However, conditioned media obtained from GFOGER hydrogels showed lower levels of secreted reparative factors. Interestingly, following injection in rats undergoing ischemia-reperfusion, treatment with CPCs encapsulated in nonadhesive RDG-presenting hydrogels resulted in the preservation of cardiac contractility and attenuation of postinfarct remodeling whereas the adhesion peptide-presenting hydrogels did not induce any functional improvement. Retention of cells was significantly higher when delivered with nonadhesive hydrogels compared to ECM-derived peptide gels. These data suggest that factors including cell differentiation state, paracrine factors and interaction with biomaterials influence the effectiveness of biomaterials-based cell therapy. A holistic consideration of these multiple variables should be included in cell-biomaterial combination therapy designs.

SUBMITTER: Bhutani S

PROVIDER: S-EPMC5812287 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Evaluation of Hydrogels Presenting Extracellular Matrix-Derived Adhesion Peptides and Encapsulating Cardiac Progenitor Cells for Cardiac Repair.

Bhutani Srishti S Nachlas Aline L Y ALY Brown Milton E ME Pete Tionne T Johnson Christopher T CT García Andres J AJ Davis Michael E ME

ACS biomaterials science & engineering 20171117 1

Cell therapy is an emerging paradigm for the treatment of heart disease. In spite of the exciting and promising preclinical results, the benefits of cell therapy for cardiac repair in patients have been modest at best. Biomaterials-based approaches may overcome the barriers of poor differentiation and retention of transplanted cells. In this study, we prepared and tested hydrogels presenting extracellular matrix (ECM)-derived adhesion peptides as delivery vehicles for c-kit<sup>+</sup> cardiac p ...[more]

PMID: 29457128

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Project description:Heart failure is a progressive deterioration of cardiac pump function over time and is often a manifestation of ischemic injury caused by myocardial infarction (MI). Post-MI, structural remodeling of the infarcted myocardium ensues. Dysregulation of extracellular matrix (ECM) homeostasis is a hallmark of structural cardiac remodeling and is largely driven by cardiac fibroblast activation. While initially adaptive, structural cardiac remodeling leads to irreversible heart failure due to the progressive loss of cardiac function. Loss of pump function is associated with myocardial fibrosis, wall thinning, and left ventricular (LV) dilatation. Surgical revascularization of the damaged myocardium via coronary artery bypass graft (CABG) surgery and/or percutaneous coronary intervention (PCI) can enhance myocardial perfusion and is beneficial. However, these interventions alone are unable to prevent progressive fibrotic remodeling and loss of heart function that leads to clinical end-stage heart failure. Acellular biologic ECM scaffolds can be surgically implanted onto injured myocardial regions during open-heart surgery as an adjunct therapy to surgical revascularization. This presents a novel therapeutic approach to alter maladaptive remodeling and promote functional recovery. Acellular ECM bioscaffolds have been shown to provide passive structural support to the damaged myocardium and also to act as a dynamic bioactive reservoir capable of promoting endogenous mechanisms of tissue repair, such as vasculogenesis. The composition and structure of xenogenic acellular ECM bioscaffolds are determined by the physiological requirements of the tissue from which they are derived. The capacity of different tissue-derived acellular bioscaffolds to attenuate cardiac remodeling and restore ECM homeostasis after injury may depend on such properties. Accordingly, the search and discovery of an optimal ECM bioscaffold for use in cardiac repair is warranted and may be facilitated by comparing bioscaffolds. This review will provide a summary of the acellular ECM bioscaffolds currently available for use in cardiac surgery with a focus on how they attenuate cardiac remodeling by providing the necessary environmental cues to promote endogenous mechanisms of tissue repair.

Dataset Information

Evaluation of Hydrogels Presenting Extracellular Matrix-Derived Adhesion Peptides and Encapsulating Cardiac Progenitor Cells for Cardiac Repair.

Publications

Evaluation of Hydrogels Presenting Extracellular Matrix-Derived Adhesion Peptides and Encapsulating Cardiac Progenitor Cells for Cardiac Repair.

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