Journal article
Cord blood stem cell expansion is permissive to epigenetic regulation and environmental cues
Experimental hematology, Vol.37(9), pp.1084-1095
09/01/2009
DOI: 10.1016/j.exphem.2009.05.012
PMCID: PMC8728741
PMID: 19501128
Abstract
Objective. Augmentation of the number of cord blood (CB) hematopoietic stem cells (HSC) present in a unit is required before it can be considered as an alternative graft for hematopoietic reconstitution for adult patients. In order to further optimize strategies to augment HSC numbers, we examined whether expansion of HSC mediated by epigenetic mechanisms remains permissive to external environmental cues.
Materials and Methods. The chromatin-modifying agents 5-aza-2'-deoxycytidine (5azaD) and trichostatin A (TSA) were used to ameliorate epigenetic alteration of CB cells during ex vivo culture by adding various cytokines. After culture, CD34(+)CD90(+) cell numbers, their division history, in vitro clonogenic potential, and in vivo hematopoietic reconstitution potential and frequency were determined.
Results. 5azaD/TSA -treated, CD34(+)CD90(+) cells were greatly influenced in terms of their degree of expansion, clonogenic potential, cell-division rate, and transplantability by the combination of cytokines used in culture. Furthermore, our current results verify that the sequential addition of 5azaD followed by TSA is crucial for expansion of HSC. We demonstrate that following 5azaD/TSA treatment, the rate of CD34(+)CD90(+) cell division is also dependent on the cytokine cocktail and that this is associated with functional changes, including alteration of in vitro clonogenic potential and in vivo reconstitution potential.
Conclusions. Our studies indicate there are interactions between intrinsic factors influenced by epigenetic mechanisms and external environmental signals in the regulation of HSC expansion. Epigenetic influences on HSC can be accentuated by environmental factors. Regulation of the rate of divisions may be a critical determinant for the maintenance of HSC functional potency during ex vivo expansion. (C) 2009 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
Details
- Title: Subtitle
- Cord blood stem cell expansion is permissive to epigenetic regulation and environmental cues
- Creators
- Hiroto Araki - University of Illinois at ChicagoSudhakar Baluchamy - University of Illinois at ChicagoKazumi Yoshinaga - University of Illinois at ChicagoBenjamin Petro - University of Illinois at ChicagoSakina Petiwala - University of Illinois at ChicagoRitesh Parajuli - University of Illinois at ChicagoMohammed Milhem - University of Illinois at ChicagoDonald Lavelle - University of Illinois at ChicagoJoseph DeSimone - University of Illinois at ChicagoNadim Mahmud - University of Illinois at Chicago
- Resource Type
- Journal article
- Publication Details
- Experimental hematology, Vol.37(9), pp.1084-1095
- Publisher
- Elsevier
- DOI
- 10.1016/j.exphem.2009.05.012
- PMID
- 19501128
- PMCID
- PMC8728741
- ISSN
- 0301-472X
- eISSN
- 1873-2399
- Number of pages
- 12
- Grant note
- State of Illinois (Illinois Regenerative Medicine Institute; Springfield, IL, USA) Leukemia & Lymphoma Society (White Plains, NY, USA) (Translational Research Program); Leukemia and Lymphoma Society
- Language
- English
- Date published
- 09/01/2009
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359699602771
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