Display options
Share it on

Int J Stem Cells. 2014 Nov;7(2):153-7. doi: 10.15283/ijsc.2014.7.2.153.

Exogenous c-Myc Blocks Differentiation and Improves Expansion of Human Erythroblasts In vitro.

International journal of stem cells

Cristopher Geiler, Inez Andrade, Daniel Greenwald

Affiliations

  1. Department of Basic Science Research, Cellologi, LLC ; Santa Barbara Cottage Hospital, Santa Barbara, USA.
  2. Department of Basic Science Research, Cellologi, LLC.

PMID: 25473453 PMCID: PMC4249898 DOI: 10.15283/ijsc.2014.7.2.153

Abstract

BACKGROUND: Engineered blood has the greatest potential to combat a predicted future shortfall in the blood supply for transfusion treatment. The production of red blood cells from hematopoietic stem cells in the laboratory is possible but the mass production of red blood cells to the level present in a blood transfusion unit is currently not possible. The proliferation capacity of the immature red blood cell will need to be increased to enable mass production. This work focused on the hypothesis that exogenous c-Myc can delay the differentiation process of highly proliferative immature erythroblasts, and increase the proliferation capacity of erythroblast cell cultures.

OBJECTIVES: The objective of this research effort was to improve in vitro erythropoiesis from stem cells without gene transfection with the eventual goal of producing blood for transfusion treatment in a manner that could be easily translated into clinical medicine.

METHODS: The hematopoietic stem cell containing mononuclear cell fraction of venous blood samples was cultured in a liquid media containing erythroblasts growth factors with and without exogenous c-Myc combined with a cell -penetrating peptide. The cells were maintained in the liquid culture media for 23 days. Viable cells were counted and analyzed with flow cytometry.

RESULTS: Our results show a 4 fold increase in expansion of the erythroblasts grown in the c-Myc containing growth media compared to the control. Eighty percent of these cells retained the CD117 surface receptor, indicating immature cells.

CONCLUSION: Exogenous c-Myc blocks the differentiation and improves in vitro expansion of human erythroblasts.

Keywords: Adult Stem Cells; Erythroblasts; Erythropoiesis; Hematopoietic Stem Cells; Proto-Oncogene Proteins c-Myc

References

  1. Oncogene. 2008 Oct 27;27(50):6462-72 - PubMed
  2. Transfusion. 2008 Jun;48(6):1122-32 - PubMed
  3. Nature. 2001 Dec 13;414(6865):768-73 - PubMed
  4. Mol Cell Biol. 2008 Dec;28(24):7286-95 - PubMed
  5. Blood. 2004 Jun 1;103(11):4310-6 - PubMed
  6. Nat Rev Cancer. 2002 Jul;2(7):489-501 - PubMed
  7. Blood. 1992 Jan 1;79(1):52-7 - PubMed
  8. Semin Cancer Biol. 2006 Aug;16(4):253-64 - PubMed
  9. Anaesthesia. 2012 May;67(5):493-500 - PubMed
  10. Transfusion. 2011 Apr;51(4):670-3 - PubMed
  11. Oncogene. 2002 May 13;21(21):3414-21 - PubMed
  12. Transfusion. 2005 Feb;45(2):141-8 - PubMed
  13. Genes Dev. 2004 Nov 15;18(22):2747-63 - PubMed
  14. Nat Rev Cancer. 2002 Oct;2(10):764-76 - PubMed
  15. Transfusion. 1995 Oct;35(10):802-12 - PubMed
  16. J Exp Med. 1978 Feb 1;147(2):324-39 - PubMed
  17. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1542-6 - PubMed
  18. Transfusion. 1993 Feb;33(2):139-44 - PubMed
  19. Annu Rev Cell Dev Biol. 2000;16:653-99 - PubMed
  20. IUBMB Life. 2010 Jul;62(7):492-6 - PubMed
  21. N Engl J Med. 1990 Jun 7;322(23):1646-51 - PubMed
  22. EMBO J. 2006 Jun 21;25(12):2723-34 - PubMed
  23. Transfusion. 2002 Oct;42(10):1253-60 - PubMed
  24. Trends Cell Biol. 2005 Mar;15(3):146-55 - PubMed

Publication Types