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A Profile of Researchers Working on Heart Decellularization

This article is a profile of one of the research groups working on decellularization and reconstruction of the heart. As is more often the case in this field these days, those involved are willing to talk about timelines for putting this research into practice. Decellularization is a promising shortcut to the creation of patient-matched organs for transplantation. A donor organ is stripped of cells until only the extracellular matrix structure and its chemical guides and signals is left. That is then populated with the patient's cells, which grow into place and rebuild the tissues. Once the technical challenges have been solved, and the methodologies made reliable, this can potentially expand the pool of donor organs to include a sizable fraction of those that at present are discarded as unsuitable due to tissue damage. It should also be possible to use animal organs as well, such as from pigs, as the decellularization process removes near all of the sources of incompatibility.

Th first thing visitors to the Texas Heart Institute's Regenerative Medicine Research labs see is a pair of large photographs. In one, a lined hand of Denton Cooley, founder of the institute, who died last November, holds a mechanical heart much like the one that he was the first to implant into a human in 1969. In the other, Doris Taylor's gloved hand holds a pig's heart so stark-white, it matches her lab coat. It is a Ghost Heart, scrubbed clean of all cells, leaving only collagen, fibronectin and laminin, which provide a protein scaffold on which to build a new human heart very nearly from scratch. One day, it will cure far more patients with bum tickers than Cooley's earlier invention ever did.

Taylor and her 25-person multidisciplinary team decellularize seven or eight hearts, mostly from rats, a week, then inject the DNA-free scaffolds with stem cells. Because muscular heart cells do not divide, they cannot regenerate on their own like, say, the bladder, an organ which has been regenerated and implanted in humans. In the case of the heart, stem cells (as opposed to heart cells) adhere to the surface of the scaffold, growing into living, functioning organs inside machines known as bioreactors, which replicate the warm, oxygen-rich environment of a heart inside a mammal's body.

The goal, of course, is to build viable organs that will pump blood through an adult's body without assistance and without the threat of rejection, since the heart will be made with the recipient's own cells. Current testing in rats has involved implanting a second heart alongside the original, in hopes that the new organ will strengthen enough inside the body to take command. Taylor estimates that it will be only 10 or 15 years before a functioning heart is implanted into an adult (pediatric hearts are smaller and require less muscle, so that could happen sooner) - "if we do it right. And what I mean by that is that although it's sexy to be first, it's better to be best." Taylor expects a fully functioning liver made from a recipient's own cells will precede the heart by several years.

Link: https://www.houstoniamag.com/articles/2017/1/23/texas-heart-institute-new-research-ghost-heart

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