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April 11, 2011

Recellularized Human Hearts May be Weeks Away

In 2008, Dr. Doris Taylor of the University of Minnesota's Center for Cardiovascular repair made a preclinical advance by the tissue engineering of a live, beating rat heart, generated using a decellularized myocardium as a scaffold, onto which cardiac stem cells were seeded.

Within two years were not only reporting similar results with reseeded decellularized lungs and livers but the transplantation and in vivo functionality (albeit for brief periods) of these constructs. And the most recent advance came at the end of 2010, with the announcement from Shay Soker, Anthony Atala, and colleagues at the Wake Forest Institute for Regenerative Medicine that

Livers from different species [mice, rats, ferrets, rabbits, and pigs] were perfused with detergent to selectively remove the cellular components of the tissue while preserving the extracellular matrix components and the intact vascular network. The decellularized vascular network was able to withstand fluid flow that entered through a central inlet vessel, branched into an extensive capillary bed, and coalesced into a single outlet vessel. The vascular network was used to reseed the scaffolds with human fetal liver and endothelial cells. These cells engrafted in their putative native locations within the decellularized organ and displayed typical endothelial, hepatic, and biliary epithelial markers, thus creating a liver-like tissue in vitro






The scientists stripped the cells from the dead hearts with a powerful detergent, leaving ‘ghost heart’ scaffolds made from the protein collagen.

The ghost hearts were then injected with millions of stem cells, which had been extracted from patients and supplied with nutrients.

The stem cells ‘recognised’ the collagen heart structure and began to turn into heart muscle cells.

The hearts have yet to start beating – but if they do, they could be strong enough to pump blood.

However, the race to create a working heart faces many obstacles.

One of the biggest is getting enough oxygen to the organ through a complex network of blood vessels. Scientists also need to ensure the heart cells beat in time.

Dr Taylor told the Sunday Times: ‘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.’


Dr Taylor points out that there is no shortage of pigs from which to extract hearts if no human cadavers are available. Once such a heart has been stripped of pig cells and reseeded with human stem cells taken from a patient needing a new heart, there should be few rejections.

“We are a long way off creating a heart suitable for transplant, but the potential is clearly there," she said. ...

A key question for regenerative medicine researchers is how to make sure stem cells turn into the right thing - so they produce cardiac cells in the heart or liver cells in the liver.

Dr Taylor believes natural scaffolds help achieve this, partly because the stem cells recognise their shape. It may also be because they are each impregnated with chemicals specific to the organ from which they were derived. ...
“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.

“Then we would build a heart to match the patient and transplant it into them. That's the dream.”

Indeed it shall be, if these press reports are accurate, and if the resulting engineered myocardia prove even transiently viable: a key milestone in progress toward a comprehensive panel of rejuvenation biotechnologies.

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