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. 1993 Sep 15;90(18):8707–8711. doi: 10.1073/pnas.90.18.8707

Release from quiescence of CD34+ CD38- human umbilical cord blood cells reveals their potentiality to engraft adults.

A A Cardoso 1, M L Li 1, P Batard 1, A Hatzfeld 1, E L Brown 1, J P Levesque 1, H Sookdeo 1, B Panterne 1, P Sansilvestri 1, S C Clark 1, et al.
PMCID: PMC47427  PMID: 7690969

Abstract

Using optimal culture conditions in which the transforming growth factor beta 1 (TGF-beta 1) inhibitory loop has been interrupted by antisense TGF-beta 1 oligonucleotides or anti-TGF-beta serum, we have compared the proliferative capacities and the abilities of the CD34+ CD38- cell populations from bone marrow and umbilical cord blood to generate early progenitors in long-term cultures. The CD34+ CD38- fraction of umbilical cord blood accounts for 4% of the CD34+ fraction compared to only 1% in bone marrow, indicating that umbilical cord blood may be relatively enriched in stem cells. We estimate that the CD34+ CD38- cells from a typical umbilical cord blood sample produce equivalent numbers of colony-forming units (CFU)-granulocyte/erythrocyte/macrophage/megakaryocyte, twice as many CFU-granulocyte/macrophage (GM) and 3 times as many burst-forming units-erythroid as the same population from an average bone marrow sample used in adult transplantation. In addition, the colonies resulting from the umbilical cord blood samples were significantly larger than those from bone marrow, indicating a greater growth potential. However, the content of later progenitors, which may be important for short-term reconstitution, was less in umbilical cord blood-derived than in bone marrow-derived cell preparations, as estimated by a 4-fold lower production of CFU-GM in long-term cultures of CD34+ CD38+ cells. This deficit is partially compensated by the higher growth capacity of the resulting CFU-GM. These studies suggest that umbilical cord blood is a suitable source of cells for adult transplantation.

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Selected References

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  1. Brandt J., Srour E. F., van Besien K., Briddell R. A., Hoffman R. Cytokine-dependent long-term culture of highly enriched precursors of hematopoietic progenitor cells from human bone marrow. J Clin Invest. 1990 Sep;86(3):932–941. doi: 10.1172/JCI114795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Broxmeyer H. E., Douglas G. W., Hangoc G., Cooper S., Bard J., English D., Arny M., Thomas L., Boyse E. A. Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells. Proc Natl Acad Sci U S A. 1989 May;86(10):3828–3832. doi: 10.1073/pnas.86.10.3828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Broxmeyer H. E., Gluckman E., Auerbach A., Douglas G. W., Friedman H., Cooper S., Hangoc G., Kurtzberg J., Bard J., Boyse E. A. Human umbilical cord blood: a clinically useful source of transplantable hematopoietic stem/progenitor cells. Int J Cell Cloning. 1990 Jan;8 (Suppl 1):76–91. doi: 10.1002/stem.5530080708. [DOI] [PubMed] [Google Scholar]
  4. Broxmeyer H. E., Hangoc G., Cooper S., Ribeiro R. C., Graves V., Yoder M., Wagner J., Vadhan-Raj S., Benninger L., Rubinstein P. Growth characteristics and expansion of human umbilical cord blood and estimation of its potential for transplantation in adults. Proc Natl Acad Sci U S A. 1992 May 1;89(9):4109–4113. doi: 10.1073/pnas.89.9.4109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Broxmeyer H. E., Kurtzberg J., Gluckman E., Auerbach A. D., Douglas G., Cooper S., Falkenburg J. H., Bard J., Boyse E. A. Umbilical cord blood hematopoietic stem and repopulating cells in human clinical transplantation. Blood Cells. 1991;17(2):313–329. [PubMed] [Google Scholar]
  6. Danielpour D., Dart L. L., Flanders K. C., Roberts A. B., Sporn M. B. Immunodetection and quantitation of the two forms of transforming growth factor-beta (TGF-beta 1 and TGF-beta 2) secreted by cells in culture. J Cell Physiol. 1989 Jan;138(1):79–86. doi: 10.1002/jcp.1041380112. [DOI] [PubMed] [Google Scholar]
  7. Dexter T. M., Allen T. D., Lajtha L. G. Conditions controlling the proliferation of haemopoietic stem cells in vitro. J Cell Physiol. 1977 Jun;91(3):335–344. doi: 10.1002/jcp.1040910303. [DOI] [PubMed] [Google Scholar]
  8. Fauser A. A., Messner H. A. Identification of megakaryocytes, macrophages, and eosinophils in colonies of human bone marrow containing neurtophilic granulocytes and erythroblasts. Blood. 1979 May;53(5):1023–1027. [PubMed] [Google Scholar]
  9. Gluckman E., Broxmeyer H. A., Auerbach A. D., Friedman H. S., Douglas G. W., Devergie A., Esperou H., Thierry D., Socie G., Lehn P. Hematopoietic reconstitution in a patient with Fanconi's anemia by means of umbilical-cord blood from an HLA-identical sibling. N Engl J Med. 1989 Oct 26;321(17):1174–1178. doi: 10.1056/NEJM198910263211707. [DOI] [PubMed] [Google Scholar]
  10. Gluckman E., Devergie A., Thierry D., Esperou-Bourdeau H., Traineau R., Gerrota J., Brossard Y., van Nifterik J., Benbunan M. Clinical applications of stem cell transfusion from cord blood and rationale for cord blood banking. Bone Marrow Transplant. 1992;9 (Suppl 1):114–117. [PubMed] [Google Scholar]
  11. Hatzfeld J., Li M. L., Brown E. L., Sookdeo H., Levesque J. P., O'Toole T., Gurney C., Clark S. C., Hatzfeld A. Release of early human hematopoietic progenitors from quiescence by antisense transforming growth factor beta 1 or Rb oligonucleotides. J Exp Med. 1991 Oct 1;174(4):925–929. doi: 10.1084/jem.174.4.925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hows J. M., Bradley B. A., Marsh J. C., Luft T., Coutinho L., Testa N. G., Dexter T. M. Growth of human umbilical-cord blood in longterm haemopoietic cultures. Lancet. 1992 Jul 11;340(8811):73–76. doi: 10.1016/0140-6736(92)90396-k. [DOI] [PubMed] [Google Scholar]
  13. Leary A. G., Ogawa M. Blast cell colony assay for umbilical cord blood and adult bone marrow progenitors. Blood. 1987 Mar;69(3):953–956. [PubMed] [Google Scholar]
  14. Lebkowski J. S., Schain L. R., Okrongly D., Levinsky R., Harvey M. J., Okarma T. B. Rapid isolation of human CD34 hematopoietic stem cells--purging of human tumor cells. Transplantation. 1992 May;53(5):1011–1019. doi: 10.1097/00007890-199205000-00009. [DOI] [PubMed] [Google Scholar]
  15. Lu L., Xiao M., Shen R. N., Grigsby S., Broxmeyer H. E. Enrichment, characterization, and responsiveness of single primitive CD34 human umbilical cord blood hematopoietic progenitors with high proliferative and replating potential. Blood. 1993 Jan 1;81(1):41–48. [PubMed] [Google Scholar]
  16. Rowley S. D., Zuehlsdorf M., Braine H. G., Colvin O. M., Davis J., Jones R. J., Saral R., Sensenbrenner L. L., Yeager A., Santos G. W. CFU-GM content of bone marrow graft correlates with time to hematologic reconstitution following autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide-purged bone marrow. Blood. 1987 Jul;70(1):271–275. [PubMed] [Google Scholar]
  17. Spitzer G., Verma D. S., Fisher R., Zander A., Vellekoop L., Litam J., McCredie K. B., Dicke K. A. The myeloid progenitor cell--its value in predicting hematopoietic recovery after autologous bone marrow transplantation. Blood. 1980 Feb;55(2):317–323. [PubMed] [Google Scholar]
  18. Terstappen L. W., Huang S., Picker L. J. Flow cytometric assessment of human T-cell differentiation in thymus and bone marrow. Blood. 1992 Feb 1;79(3):666–677. [PubMed] [Google Scholar]
  19. Terstappen L. W., Huang S., Safford M., Lansdorp P. M., Loken M. R. Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38- progenitor cells. Blood. 1991 Mar 15;77(6):1218–1227. [PubMed] [Google Scholar]
  20. Vanlemmens P., Plouvier E., Amsallem D., Racadot E., Deschaseaux M. L., Schaal J. P., Charbord P., Noir A., Hervé P. Transplantation of umbilical cord blood in neuroblastoma. Nouv Rev Fr Hematol. 1992;34(3):243–246. [PubMed] [Google Scholar]
  21. Vilmer E., Sterkers G., Rahimy C., Elion J., Broyart A., Lescoeur B., Gerota J., Loche M., Tiercy J. M., Blot P. HLA-mismatched cord blood transplantation in a patient with advanced leukemia. Bone Marrow Transplant. 1991;7 (Suppl 2):125–125. [PubMed] [Google Scholar]
  22. Wagner J. E., Broxmeyer H. E., Byrd R. L., Zehnbauer B., Schmeckpeper B., Shah N., Griffin C., Emanuel P. D., Zuckerman K. S., Cooper S. Transplantation of umbilical cord blood after myeloablative therapy: analysis of engraftment. Blood. 1992 Apr 1;79(7):1874–1881. [PubMed] [Google Scholar]
  23. Zhou Y. Q., Stanley E. R., Clark S. C., Hatzfeld J. A., Levesque J. P., Federici C., Watt S. M., Hatzfeld A. Interleukin-3 and interleukin-1 alpha allow earlier bone marrow progenitors to respond to human colony-stimulating factor 1. Blood. 1988 Dec;72(6):1870–1874. [PubMed] [Google Scholar]

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