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Post-Transplant Events

Hepatocytes of donor origin in recipient liver after hematopoietic SCT in β-thalassemia major patients

Abstract

BM and circulating cells contain stem cells with the potential to differentiate into mature cells of various organs. We determined whether stem cells transformed into hepatocytes. Biopsy specimens from liver were obtained from 11 patients who had undergone transplantation of hematopoietic stem cells from peripheral blood (eight patients) or BM (three patients). Four female patients had received transplants from a male donor and seven male patients had received transplants from a female donor. All patients had β-thalassemia major and fibrosis in biopsy specimens from the liver before hematopoietic SCT. Hematopoietic stem cell engraftment was verified by STR analysis. The biopsies were studied for the presence of donor-derived hepatocytes using FISH of interphase nuclei and immunohistochemical staining for CD45 (leukocyte common Ag), and a hepatocyte-specific Ag. All 11 recipients of sex-mismatched transplants showed evidence of complete hematopoietic donor chimerism. XY-positive hepatocytes accounted for 4–6.7% of cells in histological sections of the biopsy specimens of female patients and XX-positive hepatocytes accounted for 3–7% of cells in histological sections of the biopsy specimens of male patients. These cells were detected in liver tissue as early as 1 year and as late as 8.5 years after hematopoietic SCT. BM and circulating stem cells can differentiate into mature hepatocytes in β-thalassemia major patients who had undergone hematopoietic SCT.

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References

  1. Caterina B, Pignatti G . Thalassemia and Related Disorders. In: John PG, John F (eds). Wintrobe's Clinical Hematology, 11th edn. LWW, 2004, pp 1319–1365.

    Google Scholar 

  2. Lucarelli G, Andreani M, Angelucci E . The cure of thalassemia with bone marrow transplantation. Bone Marrow Transplant 2001; 28: S11–S13.

    Article  PubMed  Google Scholar 

  3. Bacon BR, Britton RS . The pathology of hepatic iron overload: a free radical-mediated process. Hepatology 1990; 11: 127–137.

    Article  CAS  PubMed  Google Scholar 

  4. Ishak K, Babtista A, Bianchi L, Callea F, De Groote J, Gudat F et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22: 696–699.

    Article  CAS  PubMed  Google Scholar 

  5. Angelucci E, Muretto P, Nicolucci A, Baronciani D, Erer B, Gaziev J et al. Effects of iron overload and HCV positivity in determining progression of liver fibrosis in thalassemia following bone marrow transplantation. Blood 2002; 100: 17–21.

    Article  CAS  PubMed  Google Scholar 

  6. Muretto P, Angelucci E, Lucarelli G . Reversibility of cirrhosis in patients cured of thalassemia by bone marrow transplantation. Ann Intern Med 2002; 136: 667–672.

    Article  PubMed  Google Scholar 

  7. Giardini C, Galimberti M, Lucarelli G, Polichi P, Angelucci E, Baronciani D et al. Deferrioxamine therapy accelerates clearance of iron deposits after bone marrow transplantation for thalassemia. Br J Haematol 1995; 89: 868–873.

    Article  CAS  PubMed  Google Scholar 

  8. Ehlers KH, Giardina PJ, Lesser ML, Engle MA, Hilgartner MW . Prolonged survival in patients with beta-thalassemia major treated with deferrioxamine. J Pediatr 1991; 118: 450–454.

    Article  Google Scholar 

  9. Korbling M, Katz RL, Khanna A, Ruifrok AC, Rondon G, Albitar M et al. Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cells. N Engl J Med 2002; 346: 738–746.

    Article  PubMed  Google Scholar 

  10. Bensinger WI, Martin PJ, Storer B, Clift R, Forman SJ, Negrin R et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N Engl J Med 2001; 344: 175–181.

    CAS  PubMed  Google Scholar 

  11. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143–147.

    Article  CAS  PubMed  Google Scholar 

  12. Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WWK, Gordon PL, Neel M et al. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 1999; 5: 309–313.

    Article  CAS  PubMed  Google Scholar 

  13. Fernandez M, Simon V, Herrera G, Cao C, Del Favero H, Minguell JJ . Detection of stromal cells in peripheral blood progenitor cell collections from breast cancer patients. Bone Marrow Transplant 1997; 20: 265–271.

    Article  CAS  PubMed  Google Scholar 

  14. Lazarus HM, Haynesworth SE, Gerson SL, Caplan AI . Human bone marrow-derived mesenchymal (stromal) progenitor cells (MPCs) cannot be recovered from peripheral blood progenitor cell collections. J Hematother 1997; 6: 447–455.

    Article  CAS  PubMed  Google Scholar 

  15. Huss R, Lange C, Weissinger EM, Kolb HJ, Thalmeier K . Evidence of peripheral blood-derived, plastic-adherent CD34−/low hematopoietic stem cell clones with mesenchymal stem cell characteristics. Stem Cells 2000; 18: 252–260.

    Article  CAS  PubMed  Google Scholar 

  16. Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N et al. Bone marrow as a potential source of hepatic oval cells. Science 1999; 284: 1168–1170.

    Article  CAS  PubMed  Google Scholar 

  17. Lagasse E, Connors H, Al-Dhalimy M, Reitsma M, Dohse M, Osborne L et al. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 2000; 6: 1229–1234.

    Article  CAS  PubMed  Google Scholar 

  18. Ferrari G, Cusella-De Angelis G, Coletta M, Paolucci E, Stornaiuolo A, Cossu G et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 1998; 279: 1528–1530 (Erratum, Science 1998; 281:923).

    Article  CAS  PubMed  Google Scholar 

  19. Gussoni E, Soneoka Y, Strickland CD, Buzeny EA, Khan MK, Flint AF et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 1999; 401: 390–394.

    CAS  PubMed  Google Scholar 

  20. Anderson DJ, Gage FH, Weissman IL . Can stem cells cross lineage boundaries? Nat Med 2001; 7: 393–395.

    Article  CAS  PubMed  Google Scholar 

  21. Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R et al. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 2001; 105: 369–377.

    Article  CAS  PubMed  Google Scholar 

  22. Zanjani ED, Porada CD, Crapnell KB . Production of human hepatocytes by human Lin-, CD34+/− cells in vivo. Blood 2000; 96: 494a.

    Google Scholar 

  23. Almeida-Porada G, Porada CD, Zanjani ED . Differentiation potential of human metanephric stem cells: from mesenchyme to blood and liver. Blood 2000; 96: 494a.

    Google Scholar 

  24. Farace F, Guillier M, Elias D, Guinebretiere JM, Vainchenker W, Turhan AG . In vitro and in vivo evaluation of the hematopoietic potential of liver and muscle. Blood 2000; 96: 494a–495a.

    Google Scholar 

  25. Alison MR, Poulsom R, Jeffery R, Dhilon AP, Quaglia A, Jacob J et al. Hepatocytes from non-hepatic adult stem cells. Nature 2000; 406: 257.

    Article  CAS  PubMed  Google Scholar 

  26. Theise ND, Nimmakayalu M, Gardner R, Illei PB, Morgan G, Teperman L et al. Liver from bone marrow in humans. Hepatology 2000; 32: 11–16.

    Article  CAS  PubMed  Google Scholar 

  27. Beltrami AP, Urbanek K, Kajstura J, Yan SM, Finato N, Bussani R et al. Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med 2001; 344: 1750–1757.

    Article  CAS  PubMed  Google Scholar 

  28. Brugger W, Bross KJ, GlattM, Weber F, Mertelsmann R, Kanz L . Mobilization of tumor cells and hematopoietic progenitor cells into peripheral blood of patients with solid tumors. Blood 1994; 83: 636–640.

    CAS  PubMed  Google Scholar 

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Correspondence to M Mirzania.

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Mirzania, M., Ghavamzadeh, A., Yaghmaie, M. et al. Hepatocytes of donor origin in recipient liver after hematopoietic SCT in β-thalassemia major patients. Bone Marrow Transplant 45, 694–698 (2010). https://doi.org/10.1038/bmt.2009.229

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