Julia Kim

Abstract

The rise in mortality due to cardiovascular disease has increased the need to develop an efficient regenerative therapeutic for heart failure. Numerous cell-based therapies have been investigated for myocardial regeneration; however, an optimal progenitor has yet to be discovered. Identifying a resident cell population with enhanced ability to differentiate into multiple lineages would greatly contribute to the field of stem cell-based regenerative therapy. Evidence suggests that endogenous cardiovascular progenitor cells (CPCs) that have been isolated from the heart itself express ISL1, KDR, and MESP1, and are capable of differentiating into all major cardiac lineages. The earlier developmental stage at which endogenous CPCs reside may be associated with enhanced multipotency and differentiation capacity. A clonal population of human neonatal CPCs expressing markers of early cardiovascular development was therefore selected for analysis. Based upon recent reports of differentiation into osteoblasts by cells expressing ISL1, we performed differentiation of the selected neonatal CPC into cardiovascular lineages as well as the mesodermal derivative, osteoblasts. Gene expression analysis and flow cytometry demonstrated differentiation into both cardiovascular and osteoblast lineages. To further address the relationship between an earlier developmental stage and differentiation capability, we measured the expression of mesendodermal regulatory markers, and discovered that this population of progenitor cells may reside earlier in development than previously recognized. These results suggest that neonatal cardiovascular progenitors expressing transcripts of the mesendoderm persist within the newborn human heart, exhibit enhanced differentiation capacity into various mesodermal lineages, and can be expanded for further assessment of functional and regenerative ability.

LLU Discipline

Biochemistry

Department

Basic Sciences

School

School of Medicine

First Advisor

Kearns-Jonker, Mary

Second Advisor

Pecaut, Michael

Third Advisor

Wall, Nathan

Degree Name

Master of Science (MS)

Degree Level

M.S.

Year Degree Awarded

2017

Date (Title Page)

6-2017

Language

English

Library of Congress/MESH Subject Headings

Cardiovascular Diseases - Therapy; Cardiovascular System - Physiopathology; Stem Cells; Cell Differentiation

Subject - Local

Stem cell-based regenerative therapy; Myocardial regeneration; Endogenous Cardiovascular Progenitor Cells;

Type

Thesis

Page Count

47

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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