Organ Preservation Strategies in Transplantation - An Overview

Introduction

Organ transplantation is the only effective treatment for many patients with end-stage organ failure. High-quality organs are imperative for the treatment’s success. Organ preservation gives time for the recipient preparation, laboratory investigations, planning of facilities, and organ transportation. The main goal of organ preservation is to maintain organ and tissue function during storage.

What Are the Organ Preservation Strategies in Transplantation?

There is a lack of organs for transplantation. Hence, organ preservation is an essential step. The most common transplanted organs are the heart, liver, kidneys, and lungs. Static cold storage (SCS) and dynamic organ preservation are the two organ preservation strategies.

1. Static Cold Storage (SCS): The currently accepted and widely used technique is SCS. It is the gold standard for organ preservation. It offers a simple and beneficial method to preserve and transport organs. The steps involved in SCS include:

• At zero to four degree Celsius, the organ is flushed with a preservative solution. Then, it is stored at the same temperature after immersing it in the same preservative. The low temperature causes decreased cellular activity, whereas the preservation solution is for cell protection.

Various preservation solutions for SCS are:

• Collins Solution - It was the first commercially available preservative solution. It was used for kidneys, lungs, liver, and heart graft preservation.

• Euro-Collins Solution - Collins solution was modified in composition to improve stability. In addition, it provided better protection against prolonged cold temperatures.

• The University of Wisconsin Solution - It is also called as an intracellular fluid (ICF) -type solution. It is characterized by low sodium and potassium ions. The low ions reduce cell swelling. The ICF-type solution is used for abdominal organ preservation.

• Histidine-Tryptophan-Ketoglutarate Solution (HTK) - It is also called Custodiol solution. It is used for heart and abdominal organ transplants. The Custodiol-N is the modified HTK solution. It has added amino acids and other chemicals.

• Celsior Solution - It is used for the heart, chest, and abdominal organs.

• Low-Potassium Dextran Glucose - The low-potassium dextran glucose (LPDG) solution is the gold standard for lung preservation.

The advantages of SCS are its low cost, simplicity, and easy operation. Several limitations of SCS include tissue damage caused by a prolonged low temperature, difficult assessment of donor organ function, and ischemia-reperfusion injury (IRI). IRI is also called reoxygenation injury. IRI is tissue death following blood flow to the tissues. The reason may be the lack of oxygen during storage and subsequent energy loss. It leads to limited chances of organ survival. IRI increases the risk of graft failure and reduces long-term organ survival post-transplantation.

2. Dynamic Organ Preservation: Organ assessment before transplantation is necessary due to IRI. Hence, dynamic organ preservation was introduced. It includes ex-vivo machine perfusion at different temperatures. It is an innovative technique applied to donor organs to improve their quality. It also involves organ repair and reconditioning. The advantages include maintaining blood circulation, supplying oxygen and nutrients, and removing toxins. It employs ex-vivo organ perfusion. Ex-vivo means outside the body. The different temperature techniques are normothermic machine perfusion (NMP), sub-normothermic machine perfusion (SNMP), controlled oxygen rewarming (COR), and hypothermic machine perfusion (HMP).

• NMP - NMP is done at 35 to 38 degree Celsius. It is a method of organ perfusion under normal physiological conditions. The organs are stored at body temperature. Ex-vivo lung perfusion (EVLP) is done using this strategy. Oxygen and essential nutrients are provided. Commercial portable machines for organ preservation and transport are available. EVLP shows better results as compared to routine lung transplants. NMP has the benefit of assessing organ activity. NMP can also treat the donor organ before and after transplantation. Also, prolonged preservation times can be achieved.

• SNMP - SNMP is done at 20 to 34 degree Celsius. The cell protection properties of a lower temperature are exploited in this technique. Some studies show the superiority of SNMP to SCS in liver and kidney preservation. However, more research showing additional benefits of SNMP over NMP is needed as it is a new technique.

• COR - COR works at 8 to 20 degrees. It induces a slow temperature rise. The rationale behind COR is the prevention of IRI, as the abrupt change of temperature can lead to mitochondrial damage (mitochondria is the energy-producing structure inside a cell). The practical application is in liver transplantation.

• HMP - The basis of HMP is that the mitochondrial energy is sustained at low temperatures. Graft tissue energy is restored with the metabolic substrates (for example- glucose and amino acids) provided by HMP. Belzer developed the first clinically available HMP device in the 1960s. HMP is done at zero to eight degrees. The perfusion time is limited in HMP. HMP is inherently safe. It is because the organs can be transferred to SCS if HMP fails.

What Are the Future Perspectives on Organ Preservation?

Advanced organ preservation strategies are needed to decrease organ rejection, increase the donor organ pool, and minimize the IRI effects.

Prolonged Ex-vivo Machine Perfusion and Organ Repair: The demands for organ transplantation have increased manifold. Ex-vivo machine perfusion use aims at graft repair and regeneration. It aspires to expand the donor organ pool and improve graft function after transplantation. Hence, a prolonged time is required to solve this purpose.

• Organ Repair - EVLP is one of the most studied areas for organ repair. Various strategies have been devised to ensure organ preservation success. Scientists have used antibiotics, steroids, gene therapy, and stem cells to mitigate IRI. Gene therapy is a promising option for solid organ preservation. The donor organ is pretreated with genes during cold preservation. Gene therapy is still under trial for liver transplantation. Stem cells can be delivered directly to the organ during NMP.

• Organ Regeneration - The whole organ engineering was first done in 2008. The use of NMP with stem cells for organ regeneration has received considerable clinical attention.

• Organ Immunomodulation - Immunomodulation is the activation or suppression of the immune system. Ex-vivo machine perfusion also provides an opportunity for organ immunomodulation. Due to human organ shortage, xenotransplantation is being tried. A xenotransplant is an organ transplant between the members of different species. Ex-vivo machine perfusion reduces the xenograft rejection by removing the recipient’s reactive antibodies.

Conclusion

Organ preservation strategies are costly and complex. However, tremendous progress has been made to date. Clinical trials are going on for pancreas and intestinal tissue preservation. It is a joint effort of scientists, biomedical engineers, and transplant surgeons to make organ preservation a soaring success.