By Steve Elliott our Science and Health correspondent
In a medical breakthrough, Doris Taylor and Minnesota University’s Center for Cardiovascular Repair, informed the world they had created a beating rat heart in the laboratory.
In 1998 Dr Taylor’s team had already pioneered transplanting stem cells to patients post heart attack by replacing dead heart and cardiac scar tissue with functioning heart tissue. This produced improved patient heart function, thus the availability of stem cells for creating new heart tissue was not necessarily the principle obstacle to their much more ambitious project, creating a new complete heart for transplant.
The most forbidding hurdle to creating a new heart was recreating the immensely complex architecture of the heart organ itself.
Dr Taylor and Dr Harald Ott (a research associate in the center at the time) had a eureka moment; separate the beating heart tissue cells from their collagen ‘scaffold’ thus leaving only the already existing collagen structure of the heart.
The researchers took fresh rat hearts, pumped powerful detergent solutions through the network of cardiac blood vessels that supply the organ its nutrients. The process termed ‘whole organ decellularisation’ saw the cells ‘burst like balloons’ and the resulting dead cells were then easily washed away, leaving only the matrix of fibres that form the “skeleton” of a living heart’s connective tissue – called the extracellular matrix (ECM).
Dr Harald Ott: “We just took nature’s own building blocks to build a new organ, when we saw the first contractions we were speechless.”
The white, rubbery ECMs look eerily like imagined science fiction “ghost hearts”, retaining the original organ’s 3-D structure as well as the important tubing structure network of heart blood vessels.
Next, the team removed hearts from newborn rats – newborn tissue is rich in cells that are ‘more hearty’ and more tolerant than adult cells. They then minced the newborn heart tissue to obtain undifferentiated stem cells (stem cells which have not yet become any particular kind of flesh tissue).
The researchers injected these newborn stem cells into the left ventricles of the ECM ghost hearts and remarkably the stem cells ‘recognised’ the scaffold and proceeded to differentiate into heart muscle cells on the surface of the collagen matrix – the process termed logically enough ‘whole organ recellularisation. An oxygen-nutrient solution was pumped through the remnant network of blood vessels and after four days, they detected contractions in several hearts and after eight days, they had eight hearts beating sufficiently well to pump fluid out the aorta – albeit with significantly less pumping force than a normal rat heart at about 2% of normal adult heart function.
Importantly, the new heart cells had to work together in synchrony, the team accomplished this by stimulating the new hearts with electrodes. The electrical signals propagated along the tissue and encouragingly synchronized the beats. After stimulation ceased, the hearts continued beating on for various periods of time independently, the best-performing hearts were kept beating for 40 days.
Dr Taylor: “We don’t know yet, but the heart seems to get stronger over time as we pace it with electrical stimulation and increase the delivery of cells. We’re confident we can mimic the real heart.” The next step is to encourage optimal growth at each stage of maturity.
The team’s eventual aim is to do the whole organ decellularisation / recellularisation with the heart of a human donor scaffold.
Dr Taylor: “A member of the media asked me, ‘If it’s so simple, why hasn’t someone done it before? And what I realised was that no one had done it before because no one had believed it was possible.”
However, the creation of a working heart ready for transplanting is not altogether straightforward and presents some important obstacles. One of the biggest is delivering enough oxygen to the thick organ tissue through a complex network of blood vessels. Moreover, scientists need to ensure the heart cells beat in time – this is complicated by the fact that there are many different types of heart cells which must work together in synchrony: cells responsible for electricity which must function correctly or you get arrhythmias or heart rhythm disturbance, and heart muscle cells that perform mechanical heart pumping without rest.
Another important step for regenerative medicine researchers is making sure stem cells turn into actual heart cells in the heart or liver cells in the liver. This process is not fully understood but Dr Taylor’s view is, “We believe in giving nature the tools and getting out of the way.” Put another way, there is no need to understand the details as long as you get a functioning organ at the end of the day.
Dr Taylor: “We are a long way off creating a heart for transplant, but we think we’ve opened a door to building any organ for human transplant. My ultimate goal is that one day we will be able to take a heart, probably from a pig, remove the cells and then replace them with cells grown from the patient’s own body.” The organ of a pig is attractive because pig hearts are roughly human-sized and human donor hearts are less plentiful than pig hearts.
Dr Taylor says implanting a patient’s own cells into a matrix derived from a donor organ should completely cover the collagen skeleton, provide a ‘shield’ against the recipient’s immune system and avoid the complication of organ rejection. Her goal is to “build a heart to match the patient and transplant it into them.”
Furthermore, the process, called whole organ recellularisation, can theoretically be done “with virtually any organ.”
Dr Taylor’s work is an important gigantic-tiny step towards growing your own heart, lungs, kidney, liver or pancreas to order.
The team say there is probably a very long way to go before truly functional organs might be made to order, but the race is on. A team in Hong Kong hopes to be able to replace any part of the organ damaged in heart attacks, and even recreate the natural heart pacemaker, where the electrical heartbeat stimulus originates, within five years.
History is possibly in the making, one day people may be able to live to be 150 to 200 years of age replacing worn out organs with new as required, but not yet.
Be still, my beating heart – not if Dr Taylor has anything to do with it.