University of Pittsburgh

Revolutionary Perfusion Solution for Extended Organ Preservation and Improved Transplant Outcomes

This invention introduces novel solutions and methods for machine perfusion to significantly improve organ preservation. By utilizing an oxygenated, acellular cross-linked hemoglobin solution at sub-normothermic temperatures, the technology aims to extend organ viability and enhance post-transplant function. 

Description

The core of this technology is a specialized perfusion solution containing acellular cross-linked hemoglobin in a physiologically acceptable medium. This solution, which can be tailored in composition (e.g., hemoglobin concentration, pH, osmolality, oncotic pressure), is designed for use with machine perfusion systems. The perfusion process involves circulating this oxygenated solution through an organ, typically at sub-normothermic temperatures (e.g., around 21° C.). A key innovation is the use of a low fraction of oxygen carrier, which surprisingly provides adequate oxygen delivery and carbon dioxide removal while minimizing adverse effects commonly associated with exogenous hemoglobin, such as vasoactivity and nephrotoxicity. The perfusion can be pulsatile, mimicking arterial blood flow, or continuous, resembling venous flow.

Applications

- Organ transplantation and preservation (heart, lung, liver, kidney, pancreas, small intestine, limb, extremity, tissue graft).
- Ex vivo organ manipulation and treatment (e.g., resection of diseased tissue, introduction of therapies).
- Storage and transport of organs for allogeneic transplantation or reimplantation.
- Potential for use in research settings involving organ perfusion studies.

Advantages

- Extends organ viability during storage and transport.
- Ensures adequate oxygen delivery and carbon dioxide removal for preserved organs.
- Maintains low levels of methemoglobin production, which is crucial for organ health.
- Minimizes adverse effects often seen with other preservation solutions, including vasoactivity, nephrotoxicity, and interference with macrophage function.
- Sustains mitochondrial function and ATP generation in preserved organs.

Invention Readiness

The technology is in an advanced stage of development, with substantial data generated from various studies. Experiments have demonstrated the maintenance of mitochondrial function and sustained ATP generation in perfused organs, such as liver allografts, at relevant temperatures. Data on perfusion parameters, including pH, lactate levels, perfusion pressure, oxygenation, and methemoglobin levels, have been extensively collected and analyzed, confirming the solution's efficacy in preserving organ viability and function. The solution's characteristics, such as pH, osmolality, and colloid osmotic pressure, have been carefully defined and tested.

IP Status

https://patents.google.com/patent/US10433538B2