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Bone marrow transplantation in heme oxygenase-1 deficient mouse: presentation of curative effects and analysis of the mechanisms

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • G. Kovtunovych
  • M.C. Ghosh
  • H. Ollivierre-Wilson
  • R.P. Weitzel
  • M.A. Eckhaus
  • J.F. Tisdale
  • T.A. Rouault


Loss-of-function mutation in heme oxygenase-1 (HO-1) gene leads to severe anemia, intravascular hemolysis, and endothelial tissue and kidney damage in humans. We used bone marrow transplantation (BMT) to repopulate tissues with wild type (WT) macrophages and correct the underlying cause of phenotypic developments in KO mice. We observed a profound and prolonged effect of bone marrow cells derived from WT mice on Ho-1 KO mice despite transient nature of engraftment. BMT reversed anemia, and normalized elevated readings for plasma lactate dehydrogenase and alkaline phosphatase. Damage to kidney was prevented as well, and heme and iron metabolism were normalized. Surprisingly, hematopoietic organs of the cured animals contained less than 0.5% of donor cells versus almost 3% in liver. By immunohistochemistry these cells were identified as macrophages with high induction of HO-1. The total expression of HO-1 in the livers of transplanted KOs was higher than in WT livers. Occupying the free niche in KO mouse livers, self-renewing population of WT macrophages is able to restore heme-recycling ability in HO-1 knockout mouse, prevent intravascular hemolysis and revers HO-1 deficiency phenotype. Taken together, our findings suggest cell therapy as a promising approach for developing an effective treatment for HO-1 deficiency in humans

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