A New Population of Heart Stem Cells
Researchers have discovered a new population of adult stem cells in the heart, which could augment the development of new regeneration and repair therapies for people who have suffered heart attack or heart failure, a leading cause of death.
The mammalian heart was previously thought to be a postmitotic organ with limited regenerative reserve. This belief has been challenged by the discovery of a number of multipotent stem-like cell populations. According to the paper, retrospective carbon dating suggests that about half of the cardiomyocytes in the healthy human heart are replaced during life.
The study, led by Professor Richard Harvey and his team at UNSW and Victor Chang Cardiac Research Institute (VCCRI), is published this week in the international journal Cell Stem Cell.
Professor Harvey says the findings, which used the mouse as a model system, are hugely exciting.
“The first part of our study was actually the discovery and characterization of a new population of multi-potent, adult stem cells that live in the heart – that is, stem cells that are extremely powerful in dividing, and responding to their native environment to form whatever tissue is needed for repair.
“The fact that this new group of cells are multi-potent, and highly specific to the heart, gives us great hope that when we translate these cells into the human setting, they will work well at regenerating and repairing a broken heart – or a heart that has suffered injury through heart attack or heart failure,” added Professor Harvey.
Heart disease claimed the lives of over 22,500 Australians in 2009, killing one Australian every 23 minutes.
The findings come following recent reports in scientific literature and news media that stem cells harvested from human hearts during surgery show promise for reversing heart attack damage.
The authors write, "we document CFU-Fs (colony-forming units – fibroblasts, a type of BM colony-forming cells) an additional stem-like population in the developing and adult heart, and provide evidence for their epicardial origin in development and long-term persistence in vivo.
This is the first time this new population of stem cells has been formally described, and its origins clearly defined.
“We believe this population of cells are very high up in the stem cell hierarchy, and can generate a number of progenitor cells that would exist in a healthy heart, ready for action,” said Professor Harvey. “This could bode very well for regeneration therapies that are just beginning to be trialed around the world with other populations of stem cells.”
Using the mouse model, the researchers applied genetic tools that produce indelible marks to track the origins of cells from very early in embryonic development, right through to adulthood.
“We found that the adult heart stem cells have their origins not in the bone marrow, but in an early embryonic stem cell population that gives rise to the heart itself. This means that the functions of these adult heart stem cells are likely to be highly dedicated to that organ, and thus highly tuned to its regenerative processes,” continued Professor Harvey.
Regeneration therapies involve ‘waking up’ resident stem cells and stimulating them to migrate to the site of injury in the organ or tissue itself. This differs from cell therapies in which stem cells are extracted from the heart and grown in a tissue culture dish before being directly injected or infused into the damaged area.
“We believe this population of cells are very high up in the stem cell hierarchy, and can generate a number of progenitor cells that would exist in a healthy heart, ready for action,” added Professor Harvey. “This could bode very well for regeneration therapies that are just beginning to be trialed around the world with other populations of stem cells.”
Professor Harvey will be working as part of a new Australian Research Council (ARC) funded initiative, Stem Cells Australia, to explore the potential for these cells to participate in cardiac regeneration. He says the next step will be to characterise the human cells and test them in animal models, before exploring the viability of clinical trials for patients who have had heart attacks or heart failure. It’s hoped this would begin in the next 3-5 years.
Adult Cardiac-Resident MSC-like Stem Cells with a Proepicardial Origin. James J.H. Chong, Vashe Chandrakanthan, Munira Xaymardan, Naisana S. Asli, Joan Li, Ishtiaq Ahmed, Corey Heffernan, Mary K. Menon, Christopher J. Scarlett, Amirsalar Rashidianfar, Christine Biben, Hans Zoellner, Emily K. Colvin, John E. Pimanda, Andrew V. Biankin, Bin Zhou, William T. Pu, Owen W.J. Prall, Richard P. Harvey. Cell Stem Cell, Volume 9, Issue 6, 527-540, 2 December 2011http://www.cell.com/cell-stem-cell/fulltext/S1934-5909(11)00482-6#Summary
Victor Chang Cardiac Research Institute