Finding of CCR5-\32 cord blood haemopoetic stem cells: opportunities and perspectives for treatment of patients with HIV-infection

Cover Page

Cite item


Human immunodeficiency virus type 1 (HIV-1) was isolated in 1983. However, in despite of leading scientific laboratories over theworld have studied AIDS problem almost thirty years, HIV pandemia remains one of the serious problems of health care in the areaof infectious diseases. Molecular mechanism of HIV entry into target cell involves specific interaction of viral envelope glycoprotein gp120 with CD4 molecule and chemokine receptor CCR5. Simultaneousexpression ofCD4 and CCR5 molecules observed in the CD4+ lymphocytes (T-helpers type 1, dendritic cells, monocytes, macrophages). Polymorphism CCR5-\32 is 32 base pair deletion in the CCR5 gene, a loss-of-function mutation that provides genetic resistance against HIV-1 acquisition. Mutation occurs in the Caucasian population with up to 10—15% heterozygous and 1% homozygous carriers. So, based on the hypotesis that stem cells transplantation may treat HIV infection, several scientific groups began to form a pull of haemopoetic stem cells sourses which contains such mutation. One of such perspective activities is a developing of CCR5-\32 mutationcord blood unitsinventoryconsidering HLA haplotype frequencies specific for each region on the baseof cord blood bank.

Full Text

Restricted Access

About the authors

I. A Pirozhkov

LLC «Stem cell bank Pokrovsky», Saint-Petersburg

M. A Glebova

LLC «Stem cell bank Pokrovsky», Saint-Petersburg

M. D Canaeva

LLC «Stem cell bank Pokrovsky», Saint-Petersburg

AS. S Khrupina

LLC «Stem cell bank Pokrovsky», Saint-Petersburg; I.I. Mechnikov Northwestern State Medical University, Saint-Petersburg

S. A Smirnova

LLC «Stem cell bank Pokrovsky», Saint-Petersburg; I.I. Mechnikov Northwestern State Medical University, Saint-Petersburg

D. A Ivolgin

LLC «Stem cell bank Pokrovsky», Saint-Petersburg; I.I. Mechnikov Northwestern State Medical University, Saint-Petersburg

A. B. Smolyaninov

LLC «Stem cell bank Pokrovsky», Saint-Petersburg; I.I. Mechnikov Northwestern State Medical University, Saint-Petersburg

L. Pets

StemCyte International Cord Blood Center, Covina, USA


  1. Berger E.A., Doms R. W., Fenyo E.M. et al. A new classification for HIV1. Nature1998; 391(6664):240.
  2. Samson M., Libert F., Doranz B.J. et al. Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature1996; 382t6593):722—5.
  3. Liu R., Paxton W.A., Choe S. et al. Homozygous defect in HIV-1 coreceptor accountsfor resistance of some multiply-exposed individuals to HIV-1 infection. Cell1996; 86t3):367—77.
  4. Zimmerman P.A., Buckler W.A., Alkhatib G. Inherited resistance to HIV-1conferred by an inactivating mutation in CC chemokine receptor 5: studies inpopulations with contrasting clinical phenotypes, defined racial background, andquantified risk. Mol. Med.1997; 3(1):23-36.
  5. Hutter G., Nowak E., Mossner M. Long-term control of HIV by CCR5Delta32/Delta32 stem cell transplantation. N. Eng. J. Med. 2009; 360 (7):692-8.
  6. Hutter G., Ganepola S. Eradication of HIV by transplantation of CCR5-deficienthematopoietic stem cells.Sci.WorldJ.2011; 11: 1068-76.
  7. Allers K., Hutter G., Hofmann J. et al. Evidence for the cure of HIV infection byCCR532/32 stem cell transplantation. Blood 2011; 117(10):2791-9.
  8. Deeks S.G., McCuneJ.M. Can HIV be cured with stem cell therapy? Nat. Biotechnol. 2010; 28t8):807-10.
  9. Martinson J.J., Chapman N.H., Rees D. C. et al. Global distribution of theCCR5 gene 32-basepair deletion. Nat. Genet. 1997; 16(1): 100-3.
  10. Ruiz-Ferrer M., Barroso N., Antinolo G. et al. Analysis of CCR5-Delta 32and CCR2-V64I polymorphisms in a cohort of Spanish HCV patients using realtimepolymerase chain reaction and fluorescence resonance energy transfertechnologies. J. Viral Hepat. 2004; 11(4):319-23.
  11. Gonzalez G., Park S.S., Chen D.W. et al. Identification andfrequency of CCR5Delta32/Delta32 HIV-resistant cord blood units from Houstonarea hospitals.HIV Med.2011; 12(8): 481-6.
  12. Lee S.J., Klein J., Haagenson M. et al. High-resolution donor-recipient HLA matchingcontributes to the success of unrelated donor marrow transplantation.Blood2007; 110(13):4576-83.
  13. Hutter G., Thiel E. Allogeneic transplantation of CCR5-deficient progenitor cells in apatient with HIV infection: an update after 3 years and the search for patient no. 2.AIDS2011;25(2): 273-4.
  14. Smith A.R., Wagner J.E. Alternative haematopoietic stem cell sources fortransplantation: place of umbilical cord blood. Br. J. Haematol. 2009; 147(2):246-61.
  15. Petz L. Theroleofcordbloodtransplantationinthelong-termcontrolorpossiblecureofHIV-infectedpatients. World Cord Blood Congress III;2011 Oct 27-29;Rome,Italy: 2011. p. 30-31.
  16. Rubinstein P., Dobrila L., Rosenfield R.E. et al. Processing and cryopreservation of placental/umbilical cord blood for unrelated bone marrow reconstitution. PNAS USA1995; 92(22): 10119-22.
  17. McKenna D.H., Kadidlo D.M., McCullough J. Umbilical cord blood. In: Roback J.D., Combs M.R., Grossman B.J. et al. editors. Core Principles in cellular therapy. Bethesda:AABB; 2008, p. 47-72.
  18. Marsh S.E., Parham P., Barber L.D.The HLA FactsBook. London: Academic Press; 1999.
  19. Smith A.R., Baker K. S., De For T. E. et al. Hematopoietic cell transplantation for children with acute lymphoblastic leukemia insecond complete remission: similar outcomes in recipients of unrelated marrowand umbilical cord blood versus marrow from HLA matched sibling donors. Biol. Blood Marrow Transplant. 2009; 15(9): 1086-93.
  20. Tomblyn M.B., Arora M., Baker K.S. Myeloablative hematopoietic celltransplantation for acute lymphoblastic leukemia: analysis of graft sources andlong-term outcome. J. Clin. Oncol. 2009; 27(22):3634-41.
  21. Gutman J.A. Leisenring W., Appelbaum F.R. et al. Low relapsewithout excessive transplant-related mortality following myeloablative cord bloodtransplantation for acute leukemia in complete remission: a matched cohortanalysis.Biol. Blood Marrow Transplant.2009; 15(9):1122-29.
  22. Eapen M., Rocha V., Sanz G. et al. Effect of graft source on unrelated donor haemopoietic stem-cell transplantation in adults with acute leukaemia: a retrospective analysis. The Lancet Oncology 2010; 11(7): 653-60.
  23. Brunstein C.G., Gutman J.A., Weisdorf D.J. et al. Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood. Blood 2010; 116(22): 4693-9.
  24. Zhang M.J., Davies S. M., Camitta B. M. et al. Comparison of outcomes after HLA-matched sibling and unrelated donortransplantation for children with high-risk acute lymphoblastic leukemia. Biol. Blood Marrow Transplant. 2012; 18(8):1204-10.
  25. Liu H., Rich E. S., Godley L. et al.Reduced-intensity conditioning with combinedhaploidentical and cord blood transplantation results in rapid engraftment, lowGVHD, and durable remissions. Blood2011;118(24):6438-45.
  26. Hutter G., Zaia J.A. Allogeneic haematopoietic stem cell transplantation in patientswith human immunodeficiency virus: the experiences of more than 25 years. Clin. Exp. Immunol. 2011; 163(3):284-95.
  27. Krishnan A., Forman S.J. Hematopoietic stem cell transplantation for AIDS-relatedmalignancies. Curr. Opin. Oncol. 2010; 22(5):456-60.
  28. Krishnan A., Palmer J. M., Zaia J. A. et al. HIV status doesnot affect the outcome of autologous stem cell transplantation (ASCT) for non-Hodgkin lymphoma (NHL). Biol. Blood Marrow Transplant. 2010; 16(9):1302-8.
  29. Lai Y. Adopting autologous hematopoietic stem cells with nonfunctional CCR5 andCXCR4 against HIV. Bone Marrow Transplant. 2010; 45(4): 770-1.

Copyright (c) 2013 PJSC Human Stem Cells Institute

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: ПИ № ФС 77 - 57156 от 11.03.2014.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies