Stem Cell Mechanism of Action

A recent study from Laura Shin and Daniel Peterson in Stem Cells Translational Medicine (2013; 2:33-42) attempts to clarify exactly how stem cells given as a treatment actually induce healing.  The conventional theory has been that these cells act by differentiating once inside the body, as in they change into the cell types that the body needs to repair and heal itself.  This equates to the analogy that they act as seeds that then grow into the new tissue.

However, this recent study seems to point to a different mechanism of action.The researchers used human mesenchymal stem cells in mice that were given excisional wounds that were splinted open.  The splint wound model more closely duplicates how human wounds heal by granulation and re-epithelialization (rather than by skin contraction, the normal repair mechanism in rodents).  The treated mice were given a pair of these wounds, one that received an engraftment of stem cells and the other left untreated.  The stem cells were genetically modified so the researchers could trace the cells after giving them to the mice.  There was also a control group who had similar paired wounds, but received no stem cells.

The results of this study showed that the animals that received stem cell therapy had accelerated healing when compared to the control group.  However, the stem cells themselves did not seem to be the cells directly involved in the wound repair.  The traced stem cells were abundantly evident in the treated wound just one day after delivery, but the numbers were dramatically reduced by day 5, and these cells were not even detectable in the wound bed by day 10.

The wounds that received no stem cells showed a rather significant delay in closure compared to those receiving stem cells.  The stem cells were also only engrafted into one of the paired wounds on each treated mouse, but the non-treated wound on that mouse showed a moderate improvement in healing over the non-stem cell mice as well.

The results seem to indicate that the improved closure of the wounds despite the relatively rapid decrease in engrafted stem cell numbers may be due to signalling within the wound bed that helps to modulate and direct the host's own cells.  The injected stem cells appear to recruit the patient's own stem cells to the area of injury, both at the engrafted site as well as distant sites in the body to some degree.  These signals also seem to be maintained after the engrafted stem cells are gone.  Thus the authors propose that while the stem cells are useful for healing, it is the subsequent healing response that they induce that ultimately leads to wound repair.  If this is truly the manner that stem cells are involved in the healing process, it is the signals they produce that are the key to success with future therapies.