The Guardian reported today on a “groundbreaking medical treatment that could dramatically enhance the body's ability to repair itself”. It said that the new treatment could heal serious damage caused by heart attacks, and even repair broken bones by making the body release a “flood of stem cells into the blood stream”. The newspaper said the technique is similar to the one used to collect stem cells from bone marrow donors to treat people with leukaemia. Animal trials of the treatment will begin this year.
In this study, the researchers combined the drug Mozobil with the naturally occurring growth factor VEGF to boost a type of stem cell in the blood of mice by more than 100-fold. The researchers claim that this technique could eventually be used to repair human tissue damaged by disease. The treatment is at a very early stage, and the researchers expect it to enter the animal trial phase later this year. If successful, this will be another step towards using human progenitor stem cells to regenerate damaged and diseased organs.
Dr Simon C. Pitchford and colleagues from the Leukocyte Biology Section at Imperial College London carried out this research. The work was funded by grants from the British Heart Foundation, The European Community, The Wellcome Trust and CNPq (Brazil). The study was published in the peer-reviewed scientific journal Cell Stem Cell .
In this animal study, the researchers were interested in finding a way of stimulating the release of progenitor cells from the bone marrow of mice. Progenitor cells are similar to stem cells, but are considered to be at the next step of development as they are already programmed to develop into a specific type of cell.
It is already possible to make human bone marrow release progenitor stem cells that can make fresh blood cells. The technique is used to collect cells from bone marrow donors to treat people with certain types of the blood cancer, leukaemia. The combination of the drugs Mozobil and GCSF (granulocyte colony-stimulating factor), together stimulate the release of blood progenitor stem cells, and is already used in humans for this purpose. In order to make different sorts of cells, including heart cells and bone cells, different types of progenitor stem cells are required. Getting the bone marrow to release these other subtypes of progenitor stem cells into the bloodstream was the goal of this experiment.
The sub-types of progenitor cells that the researchers were interested in were haematopoetic progenitor cells (HPCs), which make blood; endothelial progenitor cells (EPCs), which line the blood vessels and the heart; and stromal progenitor cells (SPCs), which make other tissue.
Part of the experiment involved pretreating eight to 10-week-old female mice with vascular endothelial growth factor (VEGF), GCSF or an inert substance for four days. A day later, the mice were either injected with Mozobil or other comparison drugs. An hour after the injection, blood samples were taken so that the researchers could count the number of blood cells circulating (neutrophils), and the different types of progenitor cells (HPCs, EPCs and SPCs).
Other parts of the study looked at how the combination of drugs affected other systems and functions in mice.
The researchers claim to have shown that the release of the different sub-types of progenitor cell is regulated in several different ways.
They say that a maximum release of HPCs (blood progenitor cells), occurred with a combination of the drug treatments Mozobil and a pre-treatment of GCSF. However, this combination only caused a “submaximal” release of EPCs (blood vessel and heart progenitor cells), and did not trigger the release of SPCs (other tissue) at all.
In contrast, when mice were pre-treated in an alternative way, with VEGF instead of GCSF, giving them Mozobil stimulated the release of both EPCs and SPCs while suppressing the release of HPCs. The EPCs and SPCs in this case were increased by about 100-fold.
The researchers say that the profile of progenitor stem cells and leukocytes in the blood changes “dramatically depending on the treatment protocol”.
They suggest this means that different factors and molecular mechanisms regulate the release of the different types of progenitor cells from bone marrow. This has “far reaching implications for our understanding…and the development of therapeutic strategies… for regenerative medicine”.
This is an exciting study for scientists, as it has shown in a preclinical study (before human trials) the potential of combining new compounds for stem cell research.
One of the authors is quoted as saying, “The body repairs itself all the time. We know that the skin heals over when we cut ourselves and, similarly, inside the body there are stem cells patrolling around and carrying out repair where it's needed. However, when the damage is severe, there's a limit to what the body can do.”
If this technique proves successful and safe in human trials, it may provide a way to boost the ability of tissues to mend themselves and speed up this repair process. This research is at an early stage, and more animal studies are needed. These will need to show that the release of progenitor cells can affect healing in animals with damaged tissue before human trials can be considered.