Heart Regeneration in Mammals
Recent work done in the lab of Eric olson in colloboration with Dr Hesham Sadek has shown significant similarities in the way young mice and fishes regenerate lost cardiac cells after an injury.
As time pass by cells die, we tend to lose cells and loss of cells could be bcoz of aging , physical or ischemic injury, Toxication or chemotherapy and due to any of the degenerative diseases. However organs tend to make up for lost cells to regain normal function and this regneration process can be again be achieved using different possible ways :
1) Using adult stem cells eg: blood
2) Through mature cells as observed in regeneration of liver
or a regeneration process involving both adult stem cells and mature cells.
But not all organs have equal capacity to regenerate lost cells , especially vital organs like heart, brain seems to have a very poor rate of regeneration in mammals. The same organs (especially heart) heal at a much faster rate in salamanders and fishes.
Like any other mammal, human heart also has a very poor ability to regenenerate lost cells . It is estimated that 1% of total heart cells are regenerated in entire life time of an individual, which is very less especially after an heart attack. Generally in the case of heart injury, a scar is formed and those cells lose the ability to contract.
Zebrafish played a significant role in understanding basic mechanisms underlying heart regeneration in animals. Previous work done in various different lab ( mainly in the lab of KD poss) has shown that zebrafish can recover from significant loss of cardiac cells quite quickly. when scientists removed 20% of ventrucular tissue , fishes could regenerate the lost part in a months time without any scar formation and this recovery was seen through out the life of the fish. Another important thing about regeneration of cardiomyocytes in zebrafish involves exsisting heart cells rather than adult heart stem cells.
Video of Heart regeneration in Zebrafish:
When the zebrafish heart is damaged, the wound site is rapidly sealed with a fibrin clot that stems bleeding within seconds. Following clot formation, the tissue that surrounds the heart muscle—the epicardium—gradually covers the fibrin clot via migration and cell division. Over the next few months, new cardiac muscle is produced and replaces the clot. Growth factors, like FGF1, produced by the new heart tissue, signals the cells of the epicardial layer to migrate into the heart and form new blood vessels, to provide essential blood flow to the regenerating tissue. Over time, the wounded zebrafish heart returns to nearly its original shape, size, and pumping ability — Source Youtube
There exists significant differences when it comes to structure and function of heart in mammals and fishes. Fishes have a two chambered heart while mammals have four chambered. Its a open circulation in fishes compared to blood flows through closed arteries and veins in mammals. Cardiomyocytes are mononucleated and retain the ability to proliferate the entire life in fishes , where as Cardiomyocytes are withdrawn from cell cycle and become binucleate just after birth. In spite of all the differences , embryonic mammalian heart (before septation) resembles a adult zebrafish heart.
Based on these similarities between Zebra fish and immature mammalian heart, the author’s hypothesized that mechanisms underlying the heart regeneration in Zebra fish might also be conserved in neonatal mice heart.
The results published in journal science clearly show that there is a crucial stage during development of mammals after which cardiomyocytes fail to regenerate lost cardiac cells. authors have removed 15% of cardiac tissue from ventricular apex from a 1 day old mice and saw complete regeneration of lost part in 21 days time. The molecular evidence and lineage tracing experiments demonstrated that like in the case of zebra fish , mammals also use pre existing cardiomyoctyes to repair the injury instead of adult stem cells. The regenerated heart was functionally normal as the left ventricle pumped blood normally within 2 months. However the same experimental procedure performed on a 7 day old mice failed to regenerate lost cardiac tissue. This study narrows down the window during which transition is made from regenerative heart to non regenerative heart.
Reference:
Transient regenerative potential of the neonatal mouse heart.
Porrello ER, Mahmoud AI, Simpson E, Hill JA, Richardson JA, Olson EN, Sadek HA.
Science. 2011 Feb 25;331(6020):1078-80.
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