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Updated: Sep 28, 2025
Orthotopic Rat Kidney Transplantation: A Novel and Simplified Surgical Approach
Published on: May 7, 2019
Wanted: An endothelial cell targeting atlas for nanotherapeutic delivery in allograft organs
Samuel T Liburd1,2, Audrey A Shi3, Jordan S Pober4
1MD-PhD Program, Yale School of Medicine, New Haven, Connecticut, USA.
Abstract:
Despite the profound shortage of organs available for transplant in the U.S., over 5,000 donated organs were declined for use in 2020. Many of these organs were declined due to donor comorbidities or preservation injuries that predispose grafts to rejection and loss. The risks of these poor outcomes can potentially be reduced by pre-transplant application of normothermic machine perfusion (NMP). To date, the clinical use of NMP has focused on extending preservation and improving organ assessment, but the opportunity for ex situ therapeutic delivery may be the most transformative aspect of this technology. In this Personal Viewpoint, we argue that the endothelial cells (ECs) that line the graft vasculature are an accessible, under-exploited, and attractive target for transplant therapeutics delivered during NMP. We further contend that molecularly targeted nanoparticles (NPs) represent a promising therapeutic vehicle particularly well-suited to NMP. However, to achieve this potential, we need to answer the following three key questions: (1) What EC sub-populations exist within an organ? (2) How can these cells be accessed? (3) And most important, how can preferential retention of NPs by the cells of interest be maximized? Here we argue for creating an EC-targeting atlas as a body of knowledge that answers these questions.
Insights
Normothermic machine perfusion (NMP) offers a new way to deliver therapies to donor organs before transplant. Targeting endothelial cells (ECs) with nanoparticles during NMP could improve transplant outcomes by reducing rejection.
Area of Science:
- Transplantation immunology
- Biomedical engineering
- Vascular biology
Background:
- Significant organ transplant shortages exist, with many donated organs declined due to donor health and preservation issues.
- Normothermic machine perfusion (NMP) is used for organ preservation and assessment, but its therapeutic potential is under-explored.
- Endothelial cells (ECs) lining graft vasculature are a promising target for pre-transplant therapies.
Purpose of the Study:
- To explore the potential of using normothermic machine perfusion (NMP) for ex situ therapeutic delivery to donor organs.
- To highlight endothelial cells (ECs) as a key target for therapeutic interventions during NMP.
- To propose the development of an endothelial cell-targeting atlas to guide nanoparticle (NP) delivery.
Main Methods:
- This viewpoint discusses the potential of molecularly targeted nanoparticles (NPs) for EC delivery during NMP.
- It outlines key research questions regarding EC sub-populations, accessibility, and NP retention.
- It advocates for creating a comprehensive EC-targeting knowledge base.
Main Results:
- Normothermic machine perfusion (NMP) provides an accessible platform for delivering therapeutics to donor organs.
- Molecularly targeted nanoparticles (NPs) are well-suited for delivering therapies to ECs during NMP.
- An EC-targeting atlas is proposed to optimize NP delivery and retention for improved transplant outcomes.
Conclusions:
- Ex situ therapeutic delivery via NMP, targeting ECs with NPs, represents a transformative approach in transplantation.
- Further research is needed to characterize ECs and optimize NP strategies for targeted delivery and retention.
- Developing an EC-targeting atlas is crucial for realizing the full potential of NMP-based therapies to reduce organ loss and improve graft survival.
