Effects of lethal irradiation in zebrafish and rescue by hematopoietic cell transplantation

To enable the study of hematopoietic stem cell biology, immune cell function, and leukemogenesis in zebrafish, we have developed hematopoietic cell transplantation into adult recipient animals conditioned by γ irradiation

David Traver; Alissa Winzeler; Howard M. Stern; Elizabeth A. Mayhall; David M. Langenau; Jeffrey L. Kutok; A. Thomas Look; Leonard I. Zon

2004

Scholarcy highlights

  • The study of the biologic effects of γ irradiation began over a century ago, but it was not until deployment of the atomic bomb in 1945 that the clinical manifestations of lethal total body irradiation were fully realized
  • To enable the study of hematopoietic stem cell biology, immune cell function, and leukemogenesis in zebrafish, we have developed hematopoietic cell transplantation into adult recipient animals conditioned by γ irradiation
  • Transplantation of hematopoietic cells carrying transgenes yielding red fluorescent erythrocytes and green fluorescent leukocytes showed that HCT is sufficient to rescue the minimum lethal dose, that recipient hematolymphoid tissues were repopulated by donor-derived cells, and that donor blood cell lineages can be independently visualized in living recipients
  • The minimum lethal dose is 40 Gy, as defined as the dose resulting in less than 10% survival over 30 days after irradiation
  • In animal models of cancer, irradiation has been important in the ablation of the immune response, which permits the transplantation of aberrant populations to test oncogenic potential
  • The life span of erythrocytes has been shown to increase with decreasing temperature. It has recently been demonstrated in mouse studies that transplantation of megakaryocyte/erythrocyte-restricted progenitors is sufficient for radioprotection following the minimum lethal dose. Hematopoietic failure is due to the specific loss of erythrocytes and/or platelets over the critical window of 30 days after irradiation, after which surviving host-derived hematopoietic stem cell repopulate all blood cell lineages

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