Endothelial cell provenance: an unclear role in transplant medicine

Abstract

An understanding of the interplay between both donor endothelial progenitors and the recipient endothelium (in the case of hematopoietic cell transplant) and recipient endothelial provenance upon the established donor endothelium (in the case of solid organ transplant) is unknown. It is postulated that this interplay and consequences of purported dual endothelial populations may be a component of the post-transplant disease process and contribute to complications of engraftment or rejection. To address this potential confounding and often overlooked arena of vascular biology, a directed brief overview primarily focused on literature presented over the last decade is presented herein.

Keywords: cellular transplantation; endothelial cell provenance; endothelial chimerism; hematopoietic stem cell transplantation; organ transplantation.

Figure 1

In hematopoietic stem cell transplantation, endothelial chimerism is a result of the process by which recipient endothelium is gradually repopulated by endothelial progenitor cells of donor bone marrow origin. Blue, indicates of donor origin. Red, indicates of recipient origin. Purple represents monocyte to endothelial transformation or fusion cell phenomena. Endothelial dysfunction is exacerbated by HLA and ABO disparity, along with loss of tight junction integrity, overexpression of adhesion molecules that promote leukocyte recruitment and transmigration across the endothelium. The resultant endotheliopathy contributes to the pathogenesis of graft versus host disease, sinusoidal obstruction syndrome, capillary leak, transplant associated thrombotic microangiopathy, and idiopathic pneumonia syndrome. (Figure by S. Somani).

Figure 2

In solid organ transplantation, organ derived mature senescent donor endothelial cells are transplanted with the organ graft. Here, reverse endothelial chimerism occurs as recipient-derived cells replace the donor-derived endothelial cells within the vasculature of the grafted organ. At the zone of vascular anastomosis, exposed basement membrane (yellow) may also be reendothelized by donor graft endothelial cells (facilitated by cell-to-cell contact expansion). Blue, indicates of donor origin. Red, indicates of recipient origin. Purple represents monocyte to endothelial transformation or fusion cell phenomena. Chronic alloimmune injury leads to intimal thickening, accumulation of extracellular matrix, smooth muscle cell proliferation with resultant luminal narrowing. Here an indolent host versus graft reaction results in transplant vasculopathy that is associated with long-term organ loss. (Figure by S. Somani).

Figure 3

Diagram of search methods used to perform systematic review. “PubMed” refers to the initial keyword search within the PubMed database. “Title and abstract search” refers to review of titles and abstracts and exclusion per exclusion criteria noted above. “Full article search” refers to full paper review and exclusion at that point per exclusion criteria noted above. “Screening for relevance” refers to assessment of the publications’ relevance to this review. “References cross-referenced” refers to review of the references from the original included papers and the addition of papers if they satisfied inclusion and exclusion criteria. Figure adapted from Bolado and Landin (19).