The Role of the Donor in the Repair of the Marrow Vascular Niche Following Hematopoietic Stem Cell Transplant

¹ From the University of Florida Program in Stem Cell Biology and Regenerative Medicine, Department of Pediatrics. UFHSC Box 100296, Gainesville, Florida, 32610.
² From the University of Florida Program in Stem Cell Biology and Regenerative Medicine. UFHSC Box 100296, Gainesville, Florida, 32610.
³ From the University of Florida Program in Stem Cell Biology and Regenerative Medicine, and the Blood and Marrow Transplant Program. UFHSC Box 100296, Gainesville, Florida, 32610.

^* To whom correspondence should be addressed. E-mail: slaytwb{at}peds.ufl.edu.

	Abstract

Bone marrow sinusoids maintain homeostasis between developing hematopoietic cells and the circulation, and 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: 1) 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; 2) Uptake of Ac-LDL to identify sinusoidal endothelium and GFP to identify donor; 2) Presence of the Y-chromosome to identify male donor cells in female recipients and expression of the pan-endothelial marker, MECA-32, to identify sinusoidal endothelium; 3) Use of Tie-2/GFP mice as donors or recipients, and presence of Ac-LDL to identify sinusoids. We found that sinusoids were predominantly host-derived post-transplant. 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, though this occurred at a low level compared to hematopoietic engraftment. Donor support for the repair of the marrow vascular niche may be a critical first step of hematopoietic engraftment.

This article has been cited by other articles:

				J.-J. Lataillade, O. Pierre-Louis, H. C. Hasselbalch, G. Uzan, C. Jasmin, M.-C. Martyre, M.-C. Le Bousse-Kerdiles, and on behalf of the French INSERM and the European EU Does primary myelofibrosis involve a defective stem cell niche? From concept to evidence Blood, October 15, 2008; 112(8): 3026 - 3035. [Abstract] [Full Text] [PDF]