ICF: Hollow-fiber bioreactor technology to explore mechanisms and delivery of cellular therapy during machine perfusion of donated human kidneys

Kidneys have many functions, including cleaning the blood and removing waste. If the kidneys fail a kidney transplant is almost always the best treatment. Most kidney transplants in the UK come from deceased donors.

The process of removing, transporting, and transplanting a kidney takes time and causes damage. Some kidneys which are working well in the potential organ donor cannot tolerate this damage, and therefore are not used for transplant. This lack of suitable kidneys leads to long waiting times for people with kidney failure. Some people who need a kidney transplant never get one

Many treatments have been tried to limit the damaging effects of removing, transporting, and transplanting these kidneys. One option involves a machine which pumps fluid around the kidney whilst it is outside of the body. This is called 'machine perfusion'. It allows the delivery of other treatments directly to a kidney

Our research group has shown that a cell therapy using Multipotent Adult Progenitor Cells or MAPC® cells can be delivered to a kidney during machine perfusion. The MAPC cells, taken from human bone marrow and grown in a laboratory, were delivered into the kidney through its artery. They appeared to improve the quality of the kidneys.

However, there are two main barriers preventing us using these kidneys for transplant. Firstly, it is not well understood exactly how the MAPC cells work in this setting. Secondly, the best method for delivering the MAPC cells to the kidney is not known. This research project aims to remove those barriers

To achieve this aim, I will use a new method of delivering this cell treatment. Instead of putting the MAPC cells into the kidney, the MAPC cells will be maintained in a plastic container called a 'bioreactor'. I have spent 9 months finding the best conditions to grow MAPC cells in this bioreactor. I have also used fluid from previous kidney machine perfusions and shown that this 'activates' MAPC cells in the bioreactor, which will enable them to have an impact on the kidney

Moving this project forward will involve performing machine perfusion on pairs of human kidneys. These kidneys will have been donated, but then deemed unsuitable for transplantation. We can use this valuable gift in this approved research project where the next of kin gives consent. This set of kidneys will not be transplanted after our experiments

We will include a bioreactor of MAPC cells as part of the machine perfusion device. The MAPC cells and the kidney can communicate, meaning the MAPC cells can treat the kidney. However, the MAPC cells and the kidney are in separate compartments.

This gives the unique opportunity to study the interaction between the kidney and the MAPC cells in a controlled way. Importantly, we can see what effects the kidney has on the MAPC cells. Changing the properties of the bioreactor will allow me to modify how the two communicate and interact

This is a unique type of experiment. I hope that this will answer several important questions: How are MAPC cells activated? How do MAPC cells in a bioreactor affect a human kidney?

How do they have this effect? What types of interaction are needed for them to have their effect? Answering these questions will bring us closer to transplanting kidneys using this treatment.

This could increase the number of kidneys available for transplant, reducing waiting times, and giving hope to patients on the wait list

The potential implications of this research are also more wide reaching. The processes which injure donated organs also happen in common health problems like heart attacks and strokes. For example, there are currently clinical trials looking at MAPC cells as a treatment for strokes.

New insights into how these cell therapies are activated, how they have their effect, and how they can be delivered could be applicable in a wide range of settings. Findings from this project could therefore lead to improved treatments for a much wider range of diseases