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Notch-mediated expansion of cord blood progenitors: maintenance of transcriptional and epigenetic fidelity

Leukemia volume 29, pages 1948–1951 (2015)Cite this article

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Recent advances have been made towards successful generation of human hematopoietic stem and progenitor cells (HSPCs) derived from embryonic, induced pluripotent or hematopoietic stem cells. However, whether these stem cell populations, which are generated after ex vivo manipulation, are suitable for clinical application depends on the faithful preservation of their transcriptional, epigenetic and functional properties with respect to their primary cell counterparts.

To overcome the significant delay in neutrophil recovery following cord blood (CB) transplantation (CBT), we developed methods for the ex vivo expansion of CD34+ CB-derived HSPC by culture with the Notch-ligand Delta1. When infused into patients undergoing a myeloablative CBT, these cells have been shown to provide more rapid short-term myeloid reconstitution when co-infused with a non-manipulated CB unit(s). However, infusion of ex vivo generated HSPCs for long-term hematopoietic reconstitution remains a goal in the context of stem cell transplantation and gene therapy, thus the development of methods to assess the safety of these cultured products are essential.

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Acknowledgements

This work was supported by National Heart, Lung and Blood Institute grant U01HL100395 and National Institutes of Health Ruth L. Kirschstein National Research Service Award T32CA009351 (AD) and K12CA076930 (AD), as well as Hyundai Hope on Wheels 2013 Hope Grant (AD). CD is a Damon Runyon Clinical Investigator.

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Authors and Affiliations

  1. Clinical Research Division, Pediatric Oncology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    A Dahlberg, C Delaney & I D Bernstein

  2. Department of Pediatrics, University of Washington, Seattle, Washington, USA

    A Dahlberg, C Delaney & I D Bernstein

  3. Vaccine and Infectious Disease Division, PS Statistics, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    S Woo & R Gottardo

  4. Broad Institute of MIT and Harvard, Cambridge, MA, USA

    P Boyle, A Gnirke, C Bock, B E Bernstein & A Meissner

  5. Howard Hughes Medical Institute, Chevy Chase, MD, USA

    B E Bernstein

  6. Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    B E Bernstein

Authors
  1. A Dahlberg
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  2. S Woo
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  3. C Delaney
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  4. P Boyle
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  5. A Gnirke
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  6. C Bock
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  7. B E Bernstein
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  8. A Meissner
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  9. R Gottardo
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  10. I D Bernstein
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Corresponding author

Correspondence to I D Bernstein.

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Competing interests

The Fred Hutchinson Cancer Research Center holds a patent on ‘methods for immortalizing cells’ that covers the use of Notch ligand for expansion of hematopoietic stem cells. IDB is an inventor on this patent. The remaining authors declare no conflict of interest.

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Dahlberg, A., Woo, S., Delaney, C. et al. Notch-mediated expansion of cord blood progenitors: maintenance of transcriptional and epigenetic fidelity. Leukemia 29, 1948–1951 (2015). https://doi.org/10.1038/leu.2015.61

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