How do adult stem cells work? In healthy tissue the adult stem cell population lies dormant. Dormant stem cells are activated by external trauma signals, which trigger patterns of gene expression and protein biosynthesis, thus activating the stem cells to multiply and regenerate damaged tissue. If you think of your normal tissue as a car, then the adult stem cells are the spare parts you keep in the trunk. Usually your car works well on its own, but occasionally one part or another might wear out and need replacing. Malfunctioning tissues are in a constant state of disrepair and must therefore undergo repeated cycles of regeneration. These cycles place a strain on the stem cell population, often leading to its precocious depletion and a permanent state of tissue degeneration. So, in this case, you have a car that breaks all the time and has a finite number of spare parts in its trunk (which you quickly exhaust). With minimal contention, you accept that your car is a lemon but, as it is the only one you’ve got, you must begin pursuing more creative avenues to keep it on the road.
Researchers too must be creative as they choose among different approaches for developing therapeutic strategies. One tactic is to identify the genetic basis for the cellular malfunction and correct it within the patient’s own stem cell population using gene therapy. This is done to bolster mature tissue function by ensuring that the regenerated portion of the tissue is not fraught with the same deficiencies as the original tissue. Essentially, you are taking a spare part from the trunk and fixing it before using it to fix your car.
Another approach is to transplant a healthy population of donor stem cells into the dysfunctional tissue. In this case the hope is to fix the defect whilst bypassing the shortcomings inherent to the original tissue. In other words, you decide to get your spare parts from another, and hopefully better, manufacturer.
While both gene therapy and transplantation have merit, neither is perfect. Here my analogy falls short because attempting to identify a malfunction in a cell can in no way be compared to troubleshooting a malfunctioning automobile. Three simple reasons for this are:
- We have only the tip of the iceberg in terms of understanding how cells work (unlike cars, for which we have expertise and blueprints);
- Cells are orders of magnitude more complex than any automobile, with millions of dynamic interactions and cellular processes occurring each moment to sift through; and
- Unlike a car, the successful identification of a cellular problem is not always synonymous with the identification of its practical solution (in fact, it often represents years of further research and unanticipated conundrums).
While stem cell transplantation should bypass these problems, its two main concerns are that transplanted cells might be rejected (the spare parts from the alternate manufacturer are simply incompatible), or that they might differentiate in an incorrect and uncontrolled manner resulting in a tumour.
Researchers do have their work cut out for them in developing stem cell blueprints (the automobile itself has been a work-in-progress for over a century), however networks such as this are certain proof that they are up for the challenge.