Isolation of angiogenic and arteriogenic subpopulations of peripheral blood CD31+ cells

Johnson, Brandon Arthur Lucas

Title:

Isolation of angiogenic and arteriogenic subpopulations of peripheral blood CD31+ cells

dc.contributor.advisor	Yoon, Young-Sup
dc.contributor.author	Johnson, Brandon Arthur Lucas
dc.contributor.committeeMember	Garcia, Andres
dc.contributor.committeeMember	Jun, Ho-Wook
dc.contributor.committeeMember	Park, Changwon
dc.contributor.committeeMember	Platt, Manu
dc.contributor.department	Biomedical Engineering (Joint GT/Emory Department)
dc.date.accessioned	2020-05-20T16:56:03Z
dc.date.available	2020-05-20T16:56:03Z
dc.date.created	2019-05
dc.date.issued	2019-03-11
dc.date.submitted	May 2019
dc.date.updated	2020-05-20T16:56:03Z
dc.description.abstract	Cardiovascular disease (CVD) is the leading cause of death in the world and is predicted to remain so. Vascular growth and regeneration is a critical process necessary to the successful recovery of ischemic cardiovascular injuries and diseases. Unfortunately, postnatal vascular growth is difficult to achieve especially in the case of geriatric individuals who are likely to suffer from multiple cardiovascular complications. Though several studies have investigated various neovasculogenic cell types, these cell are either rare, inconsistently isolated or their effectiveness and existence is controversial. Recently, circulating CD31+ cells were found to strongly increase vascular perfusion in animal models of limb ischemia; however, this cell population is heterogeneous and the mechanism of their neovasculogenic effects is not well understood. Our lab identified lineage marker CD14 as a means of separating CD31+ cells into angiogenic and arteriogenic fractions. This thesis uses a series of rigorous in vitro assays to characterize the phenotype of peripheral blood CD31+CD14+ and CD31+CD14- cells. Cytometric and RNA expression analyses reveal the representation of vascular repair lineages and upregulation of angiogenic genes among the CD31+CD14+ cells and an arteriogenic expression profile among CD31+CD14- cells. The observed phenotypes were further investigated using mouse models of limb ischemia. Histological analysis supports that transplanted PB-CD31+CD14+ cells rapidly induce capillary growth and angiogenesis while injected PB-CD31+CD14- cells increase smooth muscle cell recruitment and arteriogenesis. Overall, this work demonstrates the angiogenic and arteriogenic natures of circulating CD31+CD14+ and CD31+CD14- cells, respectively. This thesis also helps to uncover the mechanisms through which the less understood process of arteriogenesis occurs. These insights are significant for the further development of effective cell therapies for cardiovascular disease.
dc.description.degree	Ph.D.
dc.format.mimetype	application/pdf
dc.identifier.uri	http://hdl.handle.net/1853/62653
dc.language.iso	en_US
dc.publisher	Georgia Institute of Technology
dc.subject	Ischemia
dc.subject	Peripheral artery disease
dc.subject	Peripheral blood
dc.subject	RNA-sequencing
dc.subject	Femoral artery ligation
dc.subject	CD31
dc.subject	Cardiovascular disease
dc.subject	Angiogenesis
dc.subject	Arteriogenesis
dc.subject	Neovasculogenesis
dc.title	Isolation of angiogenic and arteriogenic subpopulations of peripheral blood CD31+ cells
dc.type	Text
dc.type.genre	Dissertation
dspace.entity.type	Publication
local.contributor.corporatename	Wallace H. Coulter Department of Biomedical Engineering
local.contributor.corporatename	College of Engineering
relation.isOrgUnitOfPublication	da59be3c-3d0a-41da-91b9-ebe2ecc83b66
relation.isOrgUnitOfPublication	7c022d60-21d5-497c-b552-95e489a06569
thesis.degree.level	Doctoral