The protein SPARC plays a key role in the development of heart muscle in the embryo. An Austrian Science Fund FWF project has discovered this previously unknown role of SPARC.
The protein has a significant effect on the activity of the genes that are responsible for the emergence of heart cells from initially undifferentiated embryonic stem cells. The results of this project, carried out at the Medical University of Vienna, may enable heart cells to be grown for use in cell therapy for heart attack patients.
There are no easy options when the heart begins running out of steam. A transplant or the implantation of an artificial heart is risky. However the use of new tissue to regenerate damaged heart muscle may well present a better alternative in future. The production of heart muscle cells has taken a big step forward as a result of research at the Medical University of Vienna, Department of Medical Biochemistry by a team led by Prof. Georg Weitzer of the Max Perutz Laboratories.
The Vienna team has succeeded in showing that SPARC plays a key role in the development of heart cells. Commenting on the findings, Prof. Weitzer said: "The heart is the first organ to form after the egg is fertilised. Messenger substances activate the program for the development of the heart muscle cells at just the right moment, resulting in the specialisation of the initially undifferentiated cells which is needed for the formation of the heart. We have now been able to demonstrate that SPARC is right at the beginning of this sequence of messengers and sparks off the growth of the heart." SPARC acts on the expression of the bmp2 and nkx2.5 genes, both pivotal in regulating heart development. And SPARC is present right at the start of this complex process.
Using "embryoid bodies" as practical laboratory model, Prof. Weitzer succeeded in analysing the complex regulation mechanisms involved in the differentiation of stem cells into heart cells. These aggregates of embryonic stem cells can be produced from existing cultures and offer a convenient model for the very early development of an embryo. Heart cells whose rhythmic beating can clearly be seen through a microscope actually develop from initially undifferentiated cells, along with other types of cells, in these aggregates.
On the scientific use of the embryoid bodies model, Prof. Weitzer explained: "The relatively simple observation of beating heart muscle cells allows us to analyse the processes that influence their development. In this way we were able to determine that embryoid bodies treated with SPARC developed significantly more quickly into beating heart muscle cells than those which did not receive any additional SPARC." Prof. Weitzer’s team also carried out an important control experiment in which the embryoid bodies were simultaneously treated with SPARC and with antibodies against SPARC. Due to their highly specific binding, these proteins inactivated SPARC and thus blocked most of the development of the heart muscle cells.
The elegant embryoid bodies test system has already enabled Prof. Weitzer to identify another protein that plays an important part in the development of heart muscle cells. The results are currently undergoing a peer review process and will be published in 2006.
These outcomes of the FWF project could mean that it will be possible to use heart muscle cells to strengthen patients’ diseased or weak hearts. This would limit risky and expensive transplantations and the use of artificial hearts to a smaller number of particularly critical cases.