Endothelial cells mitigate DNA damage and promote the regeneration of hematopoietic stem cells after radiation injury

Derek K. Zachman, Ronald P. Leon, Prerna Das, Devorah Goldman, Kimberly L. Hamlin, Chandan Guha, William Fleming

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Endothelial cells (ECs) are an essential component of the hematopoietic microenvironment, which maintains and regulates hematopoietic stem cells (HSCs). Although ECs can support the regeneration of otherwise lethally-irradiated HSCs, the mechanisms are not well understood. To further understand this phenomenon, we studied HSC regeneration from irradiated bone marrow using co-culture with human aortic ECs (HAECs). Co-culture with HAECs induced a 24-fold expansion of long-term HSCs (CD150+, lineagelo, Sca-1+, c-Kit+; CD150+LSK cells) in vitro. These cells gave rise to functional hematopoietic stem and progenitor cells (HSPCs) with colony-forming activity, multilineage reconstitution and serial transplantation potential. Furthermore, HAECs significantly reduced DNA damage in irradiated LSK cells within 24h. Remarkably, we were able to delay the exposure of irradiated bone marrow to the regenerative, HAEC-derived signals for up to 48h and still rescue functional HSCs. G-CSF is the gold standard for promoting hematopoietic regeneration in vivo. However, when compared to HAECs, in vitro G-CSF treatment promoted lineage differentiation and regenerated 5-fold fewer CD150+LSK cells. Together, our results show that HAECs are powerful, direct mitigators of HSC injury and DNA damage. Identification of the HAEC-derived factors that rescue HSCs may lead to improved therapies for hematopoietic regeneration after radiation injury.

Original languageEnglish (US)
Pages (from-to)1013-1021
Number of pages9
JournalStem Cell Research
Volume11
Issue number3
DOIs
StatePublished - 2013

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Radiation Injuries
Hematopoietic Stem Cells
DNA Damage
Regeneration
Endothelial Cells
Granulocyte Colony-Stimulating Factor
Coculture Techniques
Bone Marrow
Forensic Anthropology
Cellular Structures
Transplantation

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Medicine(all)

Cite this

Endothelial cells mitigate DNA damage and promote the regeneration of hematopoietic stem cells after radiation injury. / Zachman, Derek K.; Leon, Ronald P.; Das, Prerna; Goldman, Devorah; Hamlin, Kimberly L.; Guha, Chandan; Fleming, William.

In: Stem Cell Research, Vol. 11, No. 3, 2013, p. 1013-1021.

Research output: Contribution to journalArticle

Zachman, Derek K. ; Leon, Ronald P. ; Das, Prerna ; Goldman, Devorah ; Hamlin, Kimberly L. ; Guha, Chandan ; Fleming, William. / Endothelial cells mitigate DNA damage and promote the regeneration of hematopoietic stem cells after radiation injury. In: Stem Cell Research. 2013 ; Vol. 11, No. 3. pp. 1013-1021.
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