A Novel Population of Cardiovascular Progenitors Persist in Neonates as Mesendodermal Cells

<p>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.</p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Basic Sciences

Year

2017

Author dc:creator

• Kim, Julia

Contributors dc:contributor

• Kearns-Jonker, Mary
• Pecaut, Michael
• Wall, Nathan

• Biochemistry
• Medical Biochemistry
• Medical Sciences
• Medicine and Health Sciences
• Cardiovascular Diseases - Therapy; Cardiovascular System - Physiopathology; Stem Cells; Cell Differentiation
• Stem cell-based regenerative therapy; Myocardial regeneration; Endogenous Cardiovascular Progenitor Cells;

Statement dc: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.

Language dc:language

English

Repository record dc:identifier

https://scholarsrepository.llu.edu/etd/484

OAI identifier oai:identifier

oai:scholarsrepository.llu.edu:etd-1483