Journal article
Expansion of human umbilical cord blood SCID-repopulating cells using chromatin-modifying agents
Experimental hematology, Vol.34(2), pp.140-149
2006
DOI: 10.1016/j.exphem.2005.10.002
PMID: 16459182
Abstract
We investigated whether the addition of two chromatin-modifying agents, 5-aza-2′-deoxycytidine (5azaD) and trichostatin A (TSA), to cord blood (CB) CD34
+ cells in culture results in expansion of the numbers of severe combined immunodeficient (SCID) repopulating cells (SRC).
Human CB CD34
+ cells were cultured with cytokines in the presence or absence of 5azaD/TSA. After 9 days of culture, the fold expansion of CD34
+ and CD34
+CD90
+ cell numbers, colony-forming unit (CFU)-mix, cobblestone area-forming cell (CAFC), and SRC numbers were determined.
A 12.5-fold expansion of CD34
+CD90
+ cells was observed in the 5azaD/TSA-treated cultures in comparison to the input cell numbers. Expansion of CD34
+CD90
+ cells was associated with a 9.8-fold increase in the numbers of CFU-mix and 11.5-fold increase in CAFC. 5azaD/TSA treatment of the CB CD34
+ cells resulted in a 9.6-fold expansion of the absolute number of SRC following 9 days of culture as determined by limiting dilution analysis. Expansion of cells maintaining CD34
+CD90
+ phenotype was not due to the retention of a quiescent population of cells because all of the CD34
+CD90
+ cells in the culture had undergone cellular division. 5azaD/TSA-treated CD34
+CD90
+ cells, but not CD34
+CD90
− cells were responsible for in vivo hematopoietic repopulation potential of nonobese diabetic/SCID mice.
Ex vivo expansion strategy using chromatin-modifying agents provides a potential avenue by which to expand the number of hematopoietic stem cells (HSC) with a single CB unit for use as an alternative source of HSC grafts for adult recipients.
Details
- Title: Subtitle
- Expansion of human umbilical cord blood SCID-repopulating cells using chromatin-modifying agents
- Creators
- Hiroto Araki - University of Illinois ChicagoNadim Mahmud - University of Illinois ChicagoMohammed Milhem - University of Illinois ChicagoRafael Nunez - University of Illinois ChicagoMingjiang Xu - University of Illinois ChicagoCraig A. Beam - University of Illinois ChicagoRonald Hoffman - University of Illinois Chicago
- Resource Type
- Journal article
- Publication Details
- Experimental hematology, Vol.34(2), pp.140-149
- DOI
- 10.1016/j.exphem.2005.10.002
- PMID
- 16459182
- NLM abbreviation
- Exp Hematol
- ISSN
- 0301-472X
- eISSN
- 1873-2399
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2006
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359836302771
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