Origin of Endothelium in Human Renal Allografts

Abstract

SummarySex chromatin counts performed on the endothelial cells of 40 human kidneys transplanted to recipients of the opposite sex showed that the donor endothelium had persisted except in three poorly functioning and severely damaged grafts. In these a high proportion of the endothelial cells in peritubular capillaries and veins were derived from the host. Endothelial repopulation of organ allografts probably occurs only after severe tissue injury, and it cannot explain the phenomenon of graft adaptation. Repopulated endothelium may be derived from circulating cells.records of the sex of the donor and the recipient. The donor sex was readily confirmed by an examination of arterial smooth muscle cells, where sexual differentiation is very obvious.Most of the sections were examined without previous knowledge of the sex of the donor or the recipient. Between 300 and 1,000 endothelial cells were counted from the arteries, peritubular capillaries, vasa recta, and veins from each specimen. Sex chromatin body counts on glomerular endothelium were attempted in only three cases of special interest, for, though they can be seen in normal female glomeruli, nuclear irregularity is very common and confusion with epithelial and mesangial cells is bound to make the counts unreliable. Control values for the frequency of sex chromatin bodies were established in the sexmatched grafts and from earlier results (Sinclair, 1972) in six normal kidneys.

Origin of neointimal endothelium and α-actin–positive smooth muscle cells in transplant arteriosclerosis

“…Since then, several groups reported data supporting (11)(12)(13)(14)(15)(16) and discounting (17)(18)(19)(20)24) repopulation of graft vessels by recipient-derived ECs after solid organ transplantation (kidney, heart, and lung) (reviewed in ref. 50).…”

Donor and Recipient Origin of Mesenchymal and Endothelial Cells in Chronic Renal Allograft Remodeling

“…A similar discrepancy was described for interstitial cells as Bittmann et al (20) showed graft origin of interstitial myofibroblasts, whereas Grimm et al (21) (5) (29)(30)(31). Recipientderived ECs were predominantly observed in the peritubular capillaries (29,32,33), and the level of EC chimerism has been linked to the severity of vascular rejection (29,32) or duration of ischemia (30,31). According to these studies, one might suggest that the presence of EC chimerism appears to be a result of the severity of endothelial damage (34 (36,37).…”

The [ldquo ]privileged[rdquo ] liver and hepatic tolerogenicity

“…Studies of comparable arterial changes were not described in their human liver graft specimens and were not seen in the arteries of the native parenchymal organs of mouse radiation chimeras. However, partial arterial endothelial replacement has been documented in a small number of kidney allografts after relatively short follow-ups [5][6][7] and in 7 related donor kidneys studied by Randhawa et al 8 that had functioned for 26 to 29 years. The patchy areas of recipient vascular endothelium in these kidneys, and in the coronary arteries of cardiac allografts described by others, 9,10 were thought by Randhawa et al 8 to have followed injury or rejection of the original donor cells with replacement by recipient mononuclear or endothelial progenitor cells of bone marrow origin.…”