Investigation of a suppression of asymmetric cell kinetics (SACK) approach for ex vivo expansion of human hematopoietic stem cells

Ex vivo expansion of hematopoietic stem cells (HSCs) is a long-standing challenge faced by both researchers and clinicians. To date, no robust, efficient method for the pure, ex vivo expansion of human HSCs has been demonstrated. Previous methods primarily induced the expansion of committed hematopoietic progenitor cells (HPCs), yielding even less pure populations of HSCs. This research was based on the hypothesis that, like for other adult stem cells (ASCs), the major barrier to expanding HSCs ex vivo is in preferentially regulating the asymmetric self-renewal of HSCs without loss in their ability to produce differentiated committed HPCs. This laboratory has shown that a p53-dependent pathway specifically controls the self-renewal pattern of several types of ASCs and thereby provides an effective means for expansion of ASCs in culture. The method, which involves the use of purine metabolites to achieve suppression of asymmetric cell kinetics, is referred to as SACK. The utility of the p53-dependent pathway was investigated for directing expansion of human HSCs. In order to support this investigation, the proliferation of HPCs in in vitro cultures was repressed by culturing cells without hematopoietic growth factors and cytokines.

Department dc:contributor.department

Massachusetts Institute of Technology. Biological Engineering Division.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2006

Author dc:creator

• Taghizadeh, Rouzbeh R

Advisor dc:contributor.advisor

• James L. Sherley.

• Biological Engineering Division.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/38243

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/38243