The use of third-party packed red blood cells during ex situ normothermic machine perfusion of organs for transplantation: Underappreciated complexities?

Ex situ normothermic machine perfusion (NMP) is being used increasingly in the assessment of higher risk deceased donor organs and to facilitate prolonged organ storage. Third-party packed red blood cells (pRBCs) are often used as an oxygen carrier in the perfusate of ex situ NMP. Despite the increasing interest in NMP, comparatively little attention has been paid to the appropriate selection of pRBCs. This includes the choice of ABO blood group and Rhesus D status, the need for special requirements for selected recipients, and the necessity for traceability of blood components. Flushing organs with cold preservation solution after NMP removes the overwhelming majority of third-party allogeneic pRBCs, but residual pRBCs within the organ may have biologically relevant effects following implantation as they enter the recipient's circulation. This review considers these issues, and suggests that national transplant and blood transfusion agencies work together to develop a co-ordinated approach within each country. This is especially important given the possibility of organ re-allocation between centers after ex situ NMP, and the ongoing development of organ perfusion hubs.     

Modulation of endothelial cell proliferation by retinoid x receptor agonists

One feature that contraindicates the wide therapeutic use of natural retinoids is their adverse effects during systemic use and the lack of receptor selectivity. In contrast, synthetic retinoids are distinguishable from each other on the basis of their partial or exclusive preference in binding and activation of selective retinoid receptors. We examined the inhibitory activities of natural and synthetic retinoids for their ability to reverse basic fibroblast growth factor-induced endothelial cell proliferation. Both the naturally occurring retinoids at nanomolar concentrations reversed basic fibroblast growth factor-induced endothelial cell proliferation. Among the synthetic retinoids tested, retinoic acid receptor/retinoid x receptor pan-agonist AGN 191659 [(E)-5-[2-(5,6,7, 8-tetrahydro-3, 5,5,8,8-pentamethyl-2-naphtyl) propen-1-yl]-2-thiophenecarboxylic acid] and retinoid x receptor pan-agonist AGN 191701 [(E)-2-[2-(5,6,7,8-tetrahydro-3, 5,5,8, 8-pentamethyl-2-naphthyl) propen-1-yl]-4-thiophenecarboxylic acid] at nanomolar concentrations reversed the basic fibroblast growth factor-induced endothelial cell proliferation. Since none of the retinoic acid receptor agonists tested had any effect, the inhibitory effect of AGN 191659 could be attributed to its retinoid x receptor receptor activity. These results suggest that retinoid x receptor agonists may be more selective anti-angiogenic agents due to their ability to inhibit endothelial cell proliferation.