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Fernandes S, Brooks R, Gumbleton M, et al. SHIPi Enhances Autologous and Allogeneic Hematolymphoid Stem Cell Transplantation. EBioMedicine. 2015;2(3):205-213doi: 10.1016/j.ebiom.2015.02.004.
Fernandes, S., Brooks, R., Gumbleton, M., Park, M. Y., Russo, C. M., Howard, K. T., Chisholm, J. D., & Kerr, W. G. (2015). SHIPi Enhances Autologous and Allogeneic Hematolymphoid Stem Cell Transplantation. EBioMedicine, 2(3), 205-213. https://doi.org/10.1016/j.ebiom.2015.02.004
Fernandes, Sandra, et al. "SHIPi Enhances Autologous and Allogeneic Hematolymphoid Stem Cell Transplantation." EBioMedicine vol. 2,3 (2015): 205-213. doi: https://doi.org/10.1016/j.ebiom.2015.02.004
Fernandes S, Brooks R, Gumbleton M, Park MY, Russo CM, Howard KT, Chisholm JD, Kerr WG. SHIPi Enhances Autologous and Allogeneic Hematolymphoid Stem Cell Transplantation. EBioMedicine. 2015 Mar 01;2(3):205-213. doi: 10.1016/j.ebiom.2015.02.004. PMID: 26052545; PMCID: PMC4452032.
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EBioMedicine. 2015 Mar 01;2(3):205-213. doi: 10.1016/j.ebiom.2015.02.004.

SHIPi Enhances Autologous and Allogeneic Hematolymphoid Stem Cell Transplantation.

EBioMedicine

Sandra Fernandes, Robert Brooks, Matthew Gumbleton, Mi-Young Park, Christopher M Russo, Kyle T Howard, John D Chisholm, William G Kerr

Affiliations

  1. Dept. of Microbiology & Immunology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
  2. Dept. of Chemistry, Syracuse University, Syracuse, NY, 13210, USA.
  3. Dept. of Microbiology & Immunology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA ; Dept. of Chemistry, Syracuse University, Syracuse, NY, 13210, USA ; Dept. of Pediatrics, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.

PMID: 26052545 PMCID: PMC4452032 DOI: 10.1016/j.ebiom.2015.02.004

Abstract

Hematopoietic stem cell transplantation (HSCT) is a highly effective procedure enabling long-term survival for patients with hematologic malignancy or heritable defects. Although there has been a dramatic increase in the success rate of HSCT over the last two decades, HSCT can result in serious, sometime untreatable, disease due to toxic conditioning regimens, graft vs. host disease and required use of mismatched bone marrow in some cases. Studies utilizing germline knockout mice have discovered several candidate genes that could be targeted pharmacologically to create a more favorable environment for transplant success. SHIP1 deficiency permits improved engraftment of hematopoietic stem-progenitor cells (HS-PC) and produces a suppressive microenvironment ideal for incoming grafts. The recent development of small molecule SHIP1 inhibitors has opened a different therapeutic approach to creating transient SHIP1-deficiency. Here we show that SHIP1 inhibition (SHIPi) can mobilize functional HS-PC, accelerate hematologic recovery, and enhance donor HS-PC engraftment in both allogeneic and autologous transplant settings. We also observed the expansion of key cell populations known to suppress host-reactive cells formed during engraftment. Therefore, SHIPi represents a non-toxic, new therapeutic that has significant potential to improve the success and safety of therapies that utilize HSCT.

Keywords: 3AC; MMP-9; NK cells; SDF-1; SHIP1; SHIPi; allogeneic BMT; autologous BMT; stem cell mobilization

References

  1. Blood. 2009 Mar 26;113(13):2924-33 - PubMed
  2. Nat Immunol. 2009 Aug;10(8):907-17 - PubMed
  3. J Immunol. 2010 Apr 1;184(7):3582-9 - PubMed
  4. Nat Rev Immunol. 2012 May 25;12(6):403-16 - PubMed
  5. Nat Rev Immunol. 2007 May;7(5):340-52 - PubMed
  6. J Clin Oncol. 2009 Oct 1;27(28):4767-73 - PubMed
  7. J Immunol. 2006 Jun 15;176(12 ):7165-9 - PubMed
  8. Nature. 2011 Jun 08;474(7350):216-9 - PubMed
  9. Mol Med. 2012 Feb 10;18:65-75 - PubMed
  10. Biol Blood Marrow Transplant. 2008 Jan;14(1 Suppl 1):165-70 - PubMed
  11. Blood. 2009 Mar 26;113(13):2934-44 - PubMed
  12. Blood. 2014 Jan 16;123(3):310-1 - PubMed
  13. Mucosal Immunol. 2014 Nov;7(6):1429-39 - PubMed
  14. J Immunol. 2007 Mar 1;178(5):2893-900 - PubMed
  15. Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14541-6 - PubMed
  16. J Exp Med. 2005 Apr 18;201(8):1307-18 - PubMed
  17. Stem Cells Dev. 2014 Oct 1;23 (19):2336-51 - PubMed
  18. Stem Cells Dev. 2015 May 1;24(9):1073-81 - PubMed
  19. Blood. 2002 Nov 15;100(10):3825-7 - PubMed
  20. Science. 2002 Mar 15;295(5562):2097-100 - PubMed
  21. J Immunol. 2010 May 1;184(9):5065-74 - PubMed
  22. J Immunol. 2006 Apr 1;176(7):3958-65 - PubMed
  23. Lancet. 2009 May 2;373(9674):1550-61 - PubMed
  24. Annu Rev Immunol. 1999;17:189-220 - PubMed
  25. Gut. 2011 Feb;60(2):177-88 - PubMed
  26. Science. 2002 Mar 15;295(5562):2094-7 - PubMed
  27. J Immunol. 2009 Jul 15;183(2):975-83 - PubMed
  28. J Immunol. 2004 Dec 15;173(12 ):7324-30 - PubMed
  29. Circulation. 2001 Oct 23;104(17):2012-7 - PubMed
  30. Stem Cells. 2015 Mar;33(3):848-58 - PubMed
  31. JAMA. 2013 Dec 25;310(24):2631-9 - PubMed
  32. Blood. 2006 Jun 1;107(11):4338-45 - PubMed
  33. J Immunol. 2015 Mar 15;194(6):2847-54 - PubMed
  34. Blood. 2009 Jun 4;113(23):5720-6 - PubMed
  35. Oncogene. 2008 Sep 18;27(41):5497-510 - PubMed
  36. Nature. 1975 Jul 3;256(5512):41-3 - PubMed
  37. J Clin Invest. 2007 Aug;117(8):2197-204 - PubMed

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