Stem Cells Attracted to Injured Tissue by Substance P
Stem cells may be attracted to the injured central nervous system of patients with multiple sclerosis by virtue of the molecule known as SDF-1, which is expressed at the onset of disease. Indeed, we do know that stem cells selectively home to the central nervous system, at least from animal studies, in which adult mesenchymal stem cells are selectively found associated with areas of injury. But could there be other injury signals that attract stem cells?
We discussed previously that receptors associated with pain-related peptides, such as the kinin receptor B1, have the ability to make the disease worse or better depending on inhibition or activation, respectively. An interesting molecule called Substance P, is a peptide neurotransmitter that is released in various situations of tissue injury. We will discuss a recent paper (Hong et al. A new role of substance P as an injury-inducible messenger for mobilization of CD29(+) stromal-like cells. Nat Med. 2009 Apr;15(4):425-35) demonstrating that Substance P is associated with homing of stem cells.
The investigators describe a model system in which injury induces mobilization of a mesenchymal stem cell-like population that expresses CD29 and is involved in acceleration of wound healing.
They demonstrate that administration of Substance P in absence of injury in either mice, rabbits, or rats, induces mobilization of the CD29 cells from out of the bone marrow and into systemic circulation.
To demonstrate that the mobilized CD29 cells actually had regenerative activity, they harvested CD29 cells that were mobilized, and injected mobilized cells, together with substance P in a rabbit wound model, in which the wound is induced by alkaline injury. Engraftment of the transplanted cells, as well as acceleration of healing, was observed.
In order to make the case for clinical relevance of these observations, the investigators performed a series of experiments using human bone marrow mesenchymal stem cells as a model system for in vitro study. It was observed that Substance P augmented the rate of transmigration, induced nuclear translocation of beta-catenin, triggered cell proliferation, and stimulated the activation of ERK1 and ERK2 pathways.
The authors conclude with the statement that: “This finding highlights a previously undescribed function of substance P as a systemically acting messenger of injury and a mobilizer of CD29(+) stromal-like cells to participate in wound healing”
If indeed new stem cell mobilizers can be identified in addition to G-CSF and the Anormed compound, perhaps one day it may be possible to simply redistribute your stem cells between body compartments so as to not need to take stem cells from outside of the body.