Paul Riley
University College London
A molecular cardiologist looks into getting to the heart of his inner fish.
Newts do it, fish do it, but sadly humans and other mammals cannot repair or regenerate damaged heart tissue as adults.
Despite the modern-day promotion of healthier lifestyles (such as bans on smoking in public places and pro-fitness campaigns in the run-up to London 2012), cardiovascular disease is still on the up worldwide and, not unlike swine flu, is a true pandemic that respects no borders. As a result, and for some time now, I and others have been asking how we might become more newt-like or fish-like and repair our own hearts after a heart attack.
We have favoured looking at small resident progenitor cells which, when stimulated, might make new heart muscle and blood vessels. But a study by Bernhard Kühn and his colleagues at the Children's Hospital Boston in Massachusetts shows us another way (K. Bersell et al. Cell 138, 257–270; 2009).
They simply asked whether or not existing heart muscle can be instructed to divide and make more of the same. Apparently it can, with the help of the epidermal growth factor neuregulin (famed for its role in the nervous system), and its Erb4 receptor. While under the influence of neuregulin, some mature heart cells in mice disassemble their scaffold, re-enter the cell cycle, divide and regenerate injured muscle.
Of course, the devil is in the detail: the trick, it seems, is to have not only plenty of neuregulin, but also more heart muscle cells with one nucleus instead of two, because only the former responded to the growth factor. Unfortunately, this presents something of a conundrum where mammals are concerned. Mammalian heart-muscle cells generally become binuclear shortly after birth. Thus, for a complete fix, we are left heading back in the direction of the drawing board.
Comments
The implication is that most or all mammalian cardiac cells are binuclear. My impression is that occasional mammalian cardiac cells are binuclear but most are mononuclear. Has anyone done the counts? What evidence is there for this statement?
Posted by: Professor Stanley Salmons | October 14, 2009 02:15 PM
Post-natally most mammalian cardiomyocytes are binuclear and a number of studies have addressed this directly.
Even as far back as 1979 Thymidine 14C incorporation in rodent myocardium was assessed as part of the following classical study:
I. V. Uryvaeva, A. M. Aref''eva and V. Ya. Brodskii
Abstract Most ventricular cardiomyocytes in mice aged 5–6 days are polyploid cells. By this time 60% of the cardiomyocytes have become binuclear and a further 10% have become mononuclear polyploid cells. Binuclear cardiomyocytes are formed as a result of acytokinetic mitosis, mononuclear tetraploid cells as a result of termination of mitosis in the initial phases.
Key Words cardiomyocytes - polyploidization
Laboratory of Cytology, N. K. Kol''tsov Institute of Developmental Biology, Academy of Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten'' Éksperimental''noi Biologii i Meditsiny, Vol. 89, No. 2, pp. 219–222, February, 1980.
In normal human hearts we have a rigorous assessment by the same investigators (Brodskii et al., 1991) which reveals:
Mean myocyte ploidy in different layers of the anterior wall [of the LV] was similar: in the external layer it was 5.1 +/- 0.3 c, in the middle layer 5.5 +/- 0.3 c and in the inner layer 4.8 +/- 0.4 c. The mean percentage of binuclear myocytes in these three layers was also similar, being 61 +/- 3%, 63 +/- 4% and 54 +/- 5%, respectively.
Posted by: Paul Riley | October 14, 2009 03:24 PM
By way of a follow up, the study by Bersell and co-workers (2009), to which this JC refers, also reveals a majority of binucleated cardiomyocytes in post-natal(adult) mouse hearts; something in the order of 80% relative to only 10% mononuclear cells (see Fig. 2A and G) and reinforces the observation of only ~10% mononuclear cells in the hearts of mice of 2-3 months of age in Table S6.
Posted by: Paul Riley | October 14, 2009 03:57 PM