3. To define strategies to identify, select and assess potency in clinically relevant cell populations
The aim of this programme of work is to see how we can best identify and prepare cells which will be most effective at inducing repair of cartilage, by whatever means they do this.
Cell therapy works on the premise that cells will result in repair or regeneration of a damaged part of the body, with the hope that it will be ‘good as new’ and never wear out. There are, however, many different cells that could be used for this, depending on whether they come from the patient themselves (autologous), from someone completely different (allogeneic) or even from an animal. Also, they could come from a different part of the body, whether that is the region that is being repaired (e.g. cartilage cells or chondrocytes as in the clinical trial, ASCOT, for cartilage repair), or a population of ‘stem cells’ such as can be sourced from bone marrow or fat. This programme aims to determine if one population is better than another and find out if there are markers or molecules which we can measure on specific cells to tell us how good, or potent, they would be at effecting healing.
In more detail
Cell therapy has traditionally used the patients’ own cells (called ‘autologous’), which have usually been obtained by removing a small piece of healthy cartilage from the patient, isolating the cells from the cartilage matrix (these cells are called chondrocytes) and growing them in the lab, encouraging them to divide and multiply. This provided millions of chondrocytes which can be put back into the patient to help heal the damaged cartilage. The procedure is called Autologous Chondrocyte Implantation or ACI for short.
Another group of cells can be obtained from people’s bone marrow, called Mesenchymal Stromal or Stem Cells (MSCs for short). These cells can change the molecules that they produce depending how you grow them, producing ones typically formed in cartilage, bone or fat (hence the name ‘stem’ cells), but we now believe that they be just as important because of some anti-inflammatory molecules that they can synthesise and other molecules which send signals to the resident cells in the cartilage and bone. We and others have prepared MSCs from tissues in young or developing individuals, for example from umbilical cords. Due to their ability to produce anti-inflammatory and immune-suppressing molecules, these could be used to treat different people (ie as an ‘allogeneic’ treatment).
This work package is focussed on identifying the properties of individual populations of cells and seeing if we can identify particular features that will help us predict how well they will help patients heal and repair, ie to see how ‘potent’ they may be. One way we are using to help us do this, is by studying cells which are being used in a clinical trial which is comparing ‘stem’ cells with chondrocytes, called ASCOT (Autologous ‘Stem’ cells, Chondrocytes Or the Two). We are doing extensive studies of the properties of the cells at the time they are being used to treat the patients and seeing if any of these correlate with how the patient’s knee has healed one year later.