Doris Taylor: Recellularized Human Hearts May be Weeks Away
It has been an exciting period ever since Dr. Doris Taylor of the University of Minnesota's Center for Cardiovascular Repair outlined her results prior to publication in 2008 at the Foundation's Understanding Aging: Biomedical and Bioengineering Apporoaches conference at UCLA.
When the results were published, the popular press joined the field of rejuvenation biotechnology in hailing the major preclinical advance: the tissue engineering of a live, beating rat heart, generated using a decellularized myocardium as a scaffold, onto which cardiac stem cells were seeded.((1); see video of recellularized myocardial construct with tracer illustrating region of motion). These results were quickly expanded by Taylor's group as well as by independent investigators, who within two years were not only reporting similar results with reseeded decellularized lungs(2,3) and liver,(4) but the transplantation and in vivo functionality (albeit for brief periods) of these constructs. And the most recent advance came at the end of last year, 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.[our emphasis](5)
Dr. Taylor had let it be known to us that she was pursuing work with human research, using decellularized tissue donations for the biological scaffolds reseeded with human stem cells -- but we were not aware of just how quickly she was making progress.
According to press reports in the Daily Mail and two stories in The Australian, "‘The hearts are growing, and we hope they will show signs of beating within the next weeks."
We emphasize, again, that these are press reports. Both sources assert that Dr. Taylor made the announcement at the American College of Cardiology’s 60th Annual Scientific Session and Innovation in Intervention (i2 Summit 2011),yet neither their meeting highlights nor the online abstract viewer appear to provide any information on this pending step forward.
With that caveat, and apologies for the conventions of the sources:
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.’
National Heart Foundation chief medical adviser James Tatoulis said the results were "an incredibly exciting breakthrough" ...
“There are many hurdles to overcome to generate a fully functional heart, but the hope is that it may one day be possible to grow entire organs for transplant.” [said Dr. Taylor] ...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.
1: Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, Taylor DA. Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart. Nat Med. 2008 Feb;14(2):213-21. Epub 2008 Jan 13. PubMed PMID: 18193059.
2:. Petersen TH, Calle EA, Zhao L, Lee EJ, Gui L, Raredon MB, Gavrilov K, Yi T, Zhuang ZW, Breuer C, Herzog E, Niklason LE. Tissue-Engineered Lungs for in Vivo Implantation. . Science. 2010 Jun 28. [Epub ahead of print] PubMed PMID: 20576850.
3: Ott HC, Clippinger B, Conrad C, Schuetz C, Pomerantseva I, Ikonomou L, Kotton D, Vacanti JP. Regeneration and orthotopic transplantation of a bioartificial lung. Nat Med. 2010 Aug;16(8):927-33. Epub 2010 Jul 13. PubMed PMID: 20628374.
4: Uygun BE, Soto-Gutierrez A, Yagi H, Izamis ML, Guzzardi MA, Shulman C, Milwid J, Kobayashi N, Tilles A, Berthiaume F, Hertl M, Nahmias Y, Yarmush ML, Uygun K. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med. 2010 Jul;16(7):814-20. Epub 2010 Jun 13. PubMed PMID: 20543851; PubMed Central PMCID: PMC2930603.
5: Baptista PM, Siddiqui MM, Lozier G, Rodriguez SR, Atala A, Soker S. The use of whole organ decellularization for the generation of a vascularized liver organoid. Hepatology. 2010 Nov 12. [Epub ahead of print] PubMed PMID: 21225647.