The Role of the Donor in the Repair of the Marrow Vascular Niche Following Hematopoietic Stem Cell Transplant
Article first published online: 26 JUL 2007
Copyright © 2007 AlphaMed Press
Volume 25, Issue 11, pages 2945–2955, November 2007
How to Cite
Slayton, W. B., Li, X.-M., Butler, J., Guthrie, S. M., Jorgensen, M. L., Wingard, J. R. and Scott, E. W. (2007), The Role of the Donor in the Repair of the Marrow Vascular Niche Following Hematopoietic Stem Cell Transplant. STEM CELLS, 25: 2945–2955. doi: 10.1634/stemcells.2007-0158
- Issue published online: 2 JAN 2009
- Article first published online: 26 JUL 2007
- Manuscript Accepted: 20 JUL 2007
- Manuscript Received: 9 MAR 2007
- Marrow sinusoids;
- Hematopoietic stem cells;
Bone marrow sinusoids maintain homeostasis between developing hematopoietic cells and the circulation, and they provide niches for hematopoietic progenitors. Sinusoids are damaged by chemotherapy and radiation. Hematopoietic stem cells (HSCs) have been shown to produce endothelial progenitor cells that contribute to the repair of damaged blood vessels. Because HSCs home to the marrow during bone marrow transplant, these cells may play a role in repair of marrow sinusoids. Here, we explore the role of donor HSCs in the repair of damaged sinusoids following hematopoietic stem cell transplant. We used three methods to test this role: (a) expression of platelet endothelial cell adhesion molecule to identify endothelial progenitors and the presence of the Y chromosome to identify male donor cells in female recipients; (b) presence of the Y chromosome to identify male donor cells in female recipients, and expression of the panendothelial marker mouse endothelial cell antigen-32 to identify sinusoidal endothelium; and (c) use of Tie-2/green fluorescent protein mice as donors or recipients and presence of Dil-Ac-LDL to identify sinusoids. We found that sinusoids were predominantly host-derived posttransplant. Donor cells spread along the marrow vasculature early post-transplant in a pattern that matched stromal-derived factor-1 expression. Furthermore, these engrafting progenitors were positioned to provide physical support, as well as growth and survival signals in the form of vascular-endothelial growth factor-A. Occasionally, donor cells provide cellular “patches” in the damaged sinusoids, although this occurred at a low level compared with hematopoietic engraftment. Donor support for the repair of the marrow vascular niche may be a critical first step of hematopoietic engraftment.
Disclosure of potential conflicts of interest is found at the end of this article.