Why do some cells divide and duplicate, some grow out of control, and some grow not at all? A better understanding of these mechanisms will no doubt shed light upon such apparently unconnected processes like wound healing, cancer biology, tissue repair, and aging. Do not be surprised if the control mechanisms turn out to be similar, but the instructions different.
In cartilage repair, we are faced with a situation where the predominant cell, the chondrocyte, is relatively quiescent. In adulthood, its main job is to support the matrix that lies in between cells and comprises about 95% of the tissue. If things are going well, there is little to do, the chondrocyte is happy just chugging along at a low metabolic rate and in a low oxygen environment. When cartilage is damaged- and this may occur either through trauma or because the chondrocyte is a little lazy in supporting the matrix- these cells cannot readily be coaxed into a more active state (see Denovo NT, based upon more active juvenile chondrocytes). It is for this reason that cartilage in adults does not repair itself.
There are several methods to making cells “turn on” their manufacturing plants and repair tissue, much as they did in childhood. The source material- the DNA- is definitely there. Control triggers can be proteins such as TGF Beta, a factor also found in platelet rich plasma. Scientists have been able to turn normal cells into stem-like cells by using a “cocktail” of nuclear transcription factors that penetrate the cell nucleus and turn on DNA, hence protein synthesis. These are called induced pluripotent cells, a hot topic now in molecular biology. Can we induce cartilage cells to grow?
A company called TissueGene is trying to do just that. They are conducting a trial where the gene for TGF Beta is transfected into the patient’s cells- a form of genetic engineering- and potentially those cells will make more cartilage matrix. If present methods of cartilage repair can be likened to repairing potholes in the road, the TissueGene approach is more akin to building an entirely new road.
Many questions need to be answered, not the least of which is safety. Might there be unintended consequences of manipulating genes in cells? No doubt, we have seen this already in other diseases. Recent exciting work on HIV,
however, shows the other side of the story- a potential cure in some patients (see Sangamo, Inc) who have had their own cells altered and made resistant to the virus.
Since cartilage loss is not a fatal disease, we will have to find ways of evaluating such bold therapy lest it remain on the blackboard forever. But I am optimistic. Once the toolkit of gene control becomes better understood, the science will be applied.