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Vascular endothelial cells produce soluble factors that mediate the recovery of human hematopoietic stem cells after radiation injury.
- Source :
-
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation [Biol Blood Marrow Transplant] 2006 May; Vol. 12 (5), pp. 530-40. - Publication Year :
- 2006
-
Abstract
- The risk of terrorism with nuclear or radiologic weapons is considered to be high over the coming decade. Ionizing radiation can cause a spectrum of hematologic toxicities, from mild myelosuppression to myeloablation and death. However, the potential regenerative capacity of human hematopoietic stem cells (HSCs) after radiation injury has not been well characterized. In this study, we sought to characterize the effects of ionizing radiation on human HSCs and to determine whether signals from vascular endothelial cells could promote the repair of irradiated HSCs. Exposure of human bone marrow CD34+ cells to 400 cGy caused a precipitous decline in hematopoietic progenitor cell content and primitive cells capable of repopulating nonobese diabetic/severe combined immunodeficient mice (SCID-repopulating cells), which was not retrievable via treatment with cytokines. Conversely, culture of 400 cGy-irradiated bone marrow CD34+ cells with endothelial cells under noncontact conditions supported the differential recovery of both viable progenitor cells and primitive SCID-repopulating cells. These data illustrate that vascular endothelial cells produce soluble factors that promote the repair and functional recovery of HSCs after radiation injury and suggest that novel factors with radiotherapeutic potential can be identified within this milieu.
- Subjects :
- Animals
Bone Marrow Cells cytology
Bone Marrow Cells radiation effects
Cells, Cultured cytology
Cells, Cultured radiation effects
Cells, Cultured transplantation
Coculture Techniques
Colony-Forming Units Assay
Cytokines pharmacology
Cytokines therapeutic use
Fetal Blood cytology
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells cytology
Humans
Immunophenotyping
Mice
Mice, Inbred NOD
Mice, SCID
Transplantation, Heterologous
Endothelial Cells metabolism
Endothelium, Vascular cytology
Hematopoietic Stem Cells radiation effects
Radiation Injuries physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1083-8791
- Volume :
- 12
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 16635788
- Full Text :
- https://doi.org/10.1016/j.bbmt.2005.12.039