Progress | Published:

Stem-cell therapies for blood diseases

Naturevolume 441pages11001102 (2006) | Download Citation



For decades, transplantation of haematopoietic stem cells — either unmodified, or genetically modified to correct genetic disorders — has been used to treat disorders of the blood and immune systems. The present challenge is to reduce the risk of such transplants and increase the number of patients who can safely access this treatment. In developing countries, such ‘one-shot’ treatments are highly desirable because chronic treatments are difficult to sustain. To make these therapies more accessible and effective it will be important to improve clinical protocols and gene-delivery vectors, and to gain a deeper understanding of stem cells.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Additional information

Author Information Reprints and permissions information is available at


  1. 1

    Thomas, E. D., Lochte, H. L., Lu, W. C. & Ferrebee, J. W. Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N. Engl. J. Med. 12, 491–496 (1957).

  2. 2

    Gatti, R. A., Meuwissen, H. J., Allen, H. D., Hong, R. & Good, R. A. Immunological reconstitution of sex-linked lymphopenic immunological deficiency. Lancet 292, 1366–1369 (1968).

  3. 3

    Spangrude, G. J., Heimfeld, S. & Weissman, I. L. Purification and characterization of mouse hematopoietic stem cells. Science 241, 58–62 (1988).

  4. 4

    Thomas, E. D. Bone marrow transplantation — past, present and future (Nobel Lecture, December 8, 1990).

  5. 5

    Reisner, Y. et al. Transplantation for severe combined immunodeficiency with HLA-A,B,D,DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells. Blood 61, 341–348 (1983).

  6. 6

    O'Reilly, R. J., Keever, C. A., Small, T. N. & Brochstein J. The use of HLA-non-identical T-cell-depleted marrow transplants for correction of severe combined immunodeficiency disease. Immunodefic. Rev. 1, 273–309 (1989).

  7. 7

    Corti, P. et al. Reconstitution of lymphocyte subpopulations in children with inherited metabolic storage diseases after haematopoietic cell transplantation. Br. J. Haematol. 130, 249–255 (2005).

  8. 8

    Lucarelli, G., Andreani, M. & Angelucci, E. The cure of thalassemia by bone marrow transplantation. Blood Rev. 16, 81–85 (2002).

  9. 9

    Boulad, F. et al. Stem cell transplantation for the treatment of Fanconi anaemia using a fludarabine-based cytoreductive regimen and T-cell-depleted related HLA-mismatched peripheral blood stem cell grafts. Br. J. Haematol. 111, 1153–1157 (2000).

  10. 10

    Thomas, E. D., Lochte, H. L., Cannon, J. H., Sahler, O. D. & Ferrebee J. W. Supralethal whole body irradiation and isologous marrow transplantation in man. J. Clin. Invest. 38, 1709–1716 (1959).

  11. 11

    Aversa, F. et al. Treatment of high risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N. Engl. J. Med. 339, 1186–1193 (1998).

  12. 12

    Gregori, S., Bacchetta, R., Hauben, E., Battaglia, M. & Roncarolo, M. G. Regulatory T cells: prospective for clinical application in hematopoietic stem cell transplantation. Curr. Opin. Hematol. 12, 451–456 (2005).

  13. 13

    Bonini, C. et al. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science 276, 1719–1724 (1997).

  14. 14

    Bordignon, C. et al. Gene therapy in peripheral blood lymphocytes and bone marrow for ADA-immunodeficient patients. Science 270, 470–475 (1995).

  15. 15

    Cavazzana-Calvo, M. et al. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 28, 669–672 (2000).

  16. 16

    Aiuti, A. et al. Correction of ADA-SCID by stem cell gene therapy combined with a non-myeloablative conditioning. Science 296, 2410–2413 (2002).

  17. 17

    Ott, M. G. et al. Correction of chronic granulomatous disease by gene therapy augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nature Med. 12, 401–409 (2006).

  18. 18

    Sadelain, M. et al. Progress toward the genetic treatment of the β-thalassemias. Ann. NY Acad. Sci. 1054, 78–91 (2005).

  19. 19

    Hacein-Bey-Abina, S. et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 17, 415–419 (2003).

  20. 20

    Fischer, A., Abina, S. H., Thrasher, A., Von Kalle, C. & Cavazzana-Calvo, M. LMO2 and gene therapy for severe combined immunodeficiency. N. Engl. J. Med. 350, 2526–2527 (2004).

  21. 21

    Gaspar, H. B. et al. Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped γretroviral vector. Lancet 364, 2181–2187 (2004).

  22. 22

    Biffi, A. et al. Correction of metachromatic leukodystrophy in the mouse model by transplantation of genetically modified hematopoietic stem cells. J. Clin. Invest. 113, 1118–1129 (2004).

  23. 23

    Ferrari, G. et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 6, 1528–1530 (1998).

  24. 24

    Grompe, M. Bone marrow-derived hepatocytes. Novartis Found. Symp. 265, 20–27 (2005).

  25. 25

    Nadal-Ginard, B., Anversa, P., Kajstura, J. & Leri, A. Cardiac stem cells and myocardial regeneration. Novartis Found. Symp. 265, 142–154 (2005).

  26. 26

    De Palma, M., Venneri, M. A., Roca, C. & Naldini, L. Targeting exogenous genes to tumor angiogenesis by transplantation of genetically modified hematopoietic stem cells. Nature Med. 9, 789–795 (2003).

Download references


The author is indebted to L. Reiss and M. Cassin for the preparation of the manuscript.

Author information


  1. Istituto Scientifico San Raffaele, Università Vita Salute, Via Olgettina 58, Milan, 20132, Italy

    • Claudio Bordignon


  1. Search for Claudio Bordignon in:

Competing interests

Claudio Bordignon acts as a consultant for MolMed SpA.

About this article

Publication history


Issue Date


Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.