Date of Award

12-2012

Document Type

Thesis

Degree Name

Master of Science (MS)

Program

Biomedical Sciences

Track

Molecular Therapeutics

Research Advisor

Gerard P. Zambetti, Ph.D.

Committee

Elizabeth A. Fitzpatrick, Ph.D. Rennolds S. Ostrom, Ph.D.

Abstract

The ex vivo expansion of hematopoietic stem cells (HSCs) for transplantation has threefold importance: 1.) First, because of the rarity of stem cells there often isn’t a sufficient supply obtainable from common sources for larger children and adults. 2.) Secondly, patient morbidity and time to hematopoietic reconstitution following myeloablative preconditioning is improved by administering a larger pool of HSCs. 3.) Lastly, gene therapies for hematological diseases still require a robust supply of HSCs to offset varying degrees of inefficiency in vector mediated transfection protocols. These reasons, and others, have been an impetus for many discoveries made within four primary subdivisions within the field of HSC expansion; culture media optimization, hematopoietic gene regulation, development of small molecular compounds, and use of induced pluripotent stem cells (iPSCs). This article is a review of the current trends in HSC expansion methodology and posits that the majority of the singling mechanisms involved can be explained by the collective contribution of activating and inhibitory gene expression products interacting through regulatory homeostatic process mediated by HSC sensing of key pathway dependent thresholds.

DOI

10.21007/etd.cghs.2012.0172

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