Encapsulation of Pediatric C-kit+ Cells in Left Ventricular Myocardial Extracellular Matrix Hydrogels for Enhanced Cardiac Function Open Access

Abstract

Affecting one in 5,000 births, Hypoplastic Left Heart Syndrome (HLHS) is a congenital heart defect in which the left side of a newborn’s heart is underdeveloped.ٰ¹ Despite surgical palliation to redirect blood flow to right ventricle (RV), HLHS patients are at risk of RV hypertrophy, inefficient contractile force, and eventually RV failure.² Current treatments for HLHS include transplantation for RV failure; however, this is challenging due to limited donors and risk of rejections.² Recently, cell therapies, such as pediatric cardiac derived c-kit⁺ progenitor cells (CPCs), have been extensively investigated as a promising therapy for RV repair.³ However, complications regarding low cell retention and transient paracrine effects after injection require a more efficient mechanism of cell delivery.⁴ To improve the reparative effects of CPCs, this study aims to investigate a minimally invasive therapy that combines CPCs and porcine cardiac-derived extracellular matrix (LV cECM ) hydrogel. LV cECM  hydrogel has been proven by recent clinical trials to promote cardiac repair by mimicking the native extracellular matrix.⁵ In this study, CPCs were encapsulated in LV cECM  hydrogels to be used as a platform of cell delivery. Cellular function post encapsulation and improvements in cardiac reparative function were investigated through both in vitro and in vivo studies. Tube formation assays were performed to evaluate paracrine release and pro-angiogenic capacities of conditioned media from the 3D encapsulated CPC cultures. To evaluate the improvements in cardiac functional outcomes, these treatment groups were injected into RV failure rat model, and cardiac outcomes such as tricuspid annular plane systolic excursion (TAPSE), vessel development, and myocyte hypertrophy were analyzed.

Table of Contents

Introduction Materials and Methods Results Discussion References

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, General Biology, Cell Biology, Physiology
Keyword	Left Ventricular Myocardial Extracellular Matrix Cardiac Function Right Ventricular Dysfunction Hypoplastic Left Hear Syndrome C-kit+ Progenitor Cells
Committee Chair / Thesis Advisor	Michael Davis, Emory University Christine Ristaino, Emory University Mitchal Arbilly, Emory University

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