normothermic-machine-perfusion-of-rat-kidneys-for-transplantation

Normothermic Machine Perfusion of Rat Kidneys for Transplantation

The normothermic machine perfusion (NMP) technique is a promising organ preservation technology that provides an ex-vivo organ evaluation and intervention ...

the first affiliated hospital of Sun Yat-sen University

Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology

Sun Yat-sen University & Huayue Bio-Artificial Kidney and Renal Regeneration Research Laboratory

Acute rejection (AR) remains a major determinant of renal allograft outcomes, with the major histocompatibility complex (MHC) playing a pivotal role in its pathogenesis. Although immunosuppressive therapies have advanced, their reliance on high doses and lifelong administration increases the risks of infections, malignancies, and other serious complications. Normothermic machine perfusion (NMP) has emerged as a valuable tool in clinical transplantation, enabling organ preservation, functional assessment, and therapeutic intervention. Integrating NMP with genetic engineering approaches to modulate donor kidney MHC expression may offer a novel strategy for preventing AR.

Normothermic Machine Perfusion Combined With Modified Small Interfering RNA Targeting Beta-2-microglobulin and Class II Major Histocompatibility Complex Transactivator Mitigates Acute Rejection of Renal Allograft.

Although normothermic machine perfusion (NMP) has been employed in clinical transplantation, the efficient and standardized long-term NMP strategies for small animals remain to be explored, which may significantly facilitate fundamental biomedical research and drug evaluation. We established a straightforward rat kidney ex vivo NMP system and explored the efficacy of different perfusates by comparing various parameters, including the perfusion and metabolic parameters, renal function, histological features, acute renal injury score, and inflammation. Additionally, we implanted the kidneys after NMP and demonstrated the effectiveness and safety by comparing the survival of recipients, acute renal injury, and graft function. The kidneys were able to produce urine during NMP, and the groups with fetal bovine serum (FBS) exhibited higher urine output compared to those supplemented with bovine serum albumin (BSA). Nonetheless, the BSA group displayed more stable perfusion resistance, enhanced oxygen consumption efficacy, superior renal tubule function in electrolyte reabsorption and excretion, and reduced vessel injury and tissue inflammation. All grafts were successfully transplanted, and the BSA group showed slighter injury than FBS on postoperative 1 and 7 days and was not significantly different from the cold storage group. A supporting kidney function in vitro was achieved using the optimized NMP method with the perfusate consisting of rat peripheral blood, RPMI-1640, and BSA. This novel NMP strategy in small animal models may benefit basic studies related to organ preservation, assessment, and intervention in the future.

Article	Year
Normothermic Machine Perfusion Combined With Modified Small Interfering RNA Targeting Beta-2-microglobulin and Class II Major Histocompatibility Complex Transactivator Mitigates Acute Reject... Transplantation\| PubMed ID: 41145403	2026
Optimization of Rat Kidney Normothermic Machine Perfusion With Bovine Serum Albumin Perfusate: Improving Renal Function and Transplant Outcomes. FASEB journal : official publication of the Federation of American Societies for Experimental Biology\| PubMed ID: 41335037	2025

Kaixin Lan

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