Friday, 29 November 2013

Researchers identify stem cell population responsible for heart regeneration

Some vertebrates seem to have found the fountain of youth, at least when it comes to their heart. In many amphibians and fish, for example, this important organ has a marked capacity for regeneration and self-healing.

There are even some species that have perfected this capability and can completely repair damage caused to heart tissue, thus maintaining the organ's full functionality.

However, up until recently it was widely accepted that the mammalian heart had little to no regenerative capacity. However, scientists now know that heart muscle cells constantly regenerate, although at a very low rate.

Today, researchers in Thomas Braun's Research Group at the Max Planck Institute for Heart and Lung Research in Bad Nauheim, Germany announced that they have identified a stem cell population responsible for this regeneration. Hopes are growing that it will be possible in future to stimulate the self-healing powers of patients with diseases and disorders of the heart muscle, and thus develop new potential treatments.

The researchers identified this stem cell population while conducting experiments on genetically modified mice. The experiments showed that Sca1 stem cells in a healthy heart are involved in the ongoing replacement of heart muscle cells. The Sca-1 cells increase their activity if the heart is damaged, with the result that significantly more new heart muscle cells are formed.

Stem cells play a part in heart regeneration. This image of the fluorescence microscope depicts a section of the heart tissue of a mouse. The green colouring of the cells in the middle shows that the cell originated from a Sca1 stem cell. (Credit: © MPI for Heart and Lung Research)

Since, in comparison to the large amount of heart muscle cells, Sca-1 stem cells account for just a tiny proportion of the cells in the heart muscle, searching for them is like searching for a needle in a haystack. 

"We also faced the problem that Sca-1 is no longer available in the cells as a marker protein for stem cells after they have been changed into heart muscle cells. To prove this, we had to be inventive." says project leader Shizuka Uchida. 

The Max Planck researchers genetically modified the stem cells to such an extent that, in addition to the Sca-1, they produced another visible marker. Even if Sca-1 was subsequently no longer visible, the marker could still be detected permanently.

"In this way, we were able to establish that the proportion of heart muscle cells originating from Sca-1 stem cells increased continuously in healthy mice. Around five percent of the heart muscle cells regenerated themselves within 18 months." said Uchida. 

Moreover, mice suffering from heart disease triggered by the experiment had up to three times more of these newly formed heart muscle cells.

"The data shows that, in principle, the mammalian heart is able to trigger regeneration and renewal processes. Under normal circumstances, however, these processes are not enough to ultimately repair cardiac damage." said Braun.

The aim is to find ways in which the formation of new heart muscle cells from heart stem cells can be improved and thereby strengthen the heart's self-healing powers.

- Uchida S, De Gaspari P, Kostin S, Jenniches K, Kilic A, Izumiya Y, Shiojima I, Grosse Kreymborg K, Renz H, Walsh K, & Braun T (2013). Sca1-Derived Cells Are a Source of Myocardial Renewal in the Murine Adult Heart. Stem cell reports, 1 (5), 397-410 PMID: 24286028 

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