The decellularized matrix hack: skipping many steps in tissue engineering

The concept of decellularizing complex organs in cadavers and reseeding the remaining matrix structure with differentiated, stem or progenitor cells, growing in a bioreactor and transplanting back to the organism could turn out to be a real technological shortcut in the field of tissue engineering. It is not a brand new story on the web, but it is quite new in science and when I heard Doris Taylor at the Understanding Aging Conference talking on that….well I was really amazed.

Dr. Taylor not only showed the pictures of a complete decellularized rat heart matrix, but in fact they did it on a whole rat framework. So the obvious question is whether the technique could be extended to complete human cadavers (imagine the bone and the bone marrow situation) and if yes, when and how? I am sure if there were a useful clinical near term application of this type of tissue engineering, people would include that option too into their testaments.

And now a pop video on the topic and the abstract:

Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart
Harald C Ott, Thomas S Matthiesen, Saik-Kia Goh, Lauren D Black3, Stefan M Kren, Theoden I Netoff & Doris A Taylor
Nature Medicine 14, 213 – 221 2008

About 3,000 individuals in the United States are awaiting a donor heart; worldwide, 22 million individuals are living with heart failure. A bioartificial heart is a theoretical alternative to transplantation or mechanical left ventricular support. Generating a bioartificial heart requires engineering of cardiac architecture, appropriate cellular constituents and pump function. We decellularized hearts by coronary perfusion with detergents, preserved the underlying extracellular matrix, and produced an acellular, perfusable vascular architecture, competent acellular valves and intact chamber geometry. To mimic cardiac cell composition, we reseeded these constructs with cardiac or endothelial cells. To establish function, we maintained eight constructs for up to 28 d by coronary perfusion in a bioreactor that simulated cardiac physiology. By day 4, we observed macroscopic contractions. By day 8, under physiological load and electrical stimulation, constructs could generate pump function (equivalent to about 2% of adult or 25% of 16-week fetal heart function) in a modified working heart preparation.

5 thoughts on “The decellularized matrix hack: skipping many steps in tissue engineering

  1. Some days ago I read an article (in a press newsfeed, which arguably isn´t the best source for scientific details, but it´s the cheapest until I get back at university in two days) about a man in the UK who is going to try to perform transplants using genetically engineered pigs (six human genes, in theory) as a source. While I doubt that THAT experiment in particular will have much success (pig organs likely have a lot of antigens that will cause an hyperacute rejection reaction -and as a sidenote, I really hope he tries it with a loin first, because otherwise he might kill somebody-), I´m curious about whether a combination of the matrix hack and this would produce viable organs for transplant.

  2. Soft-updates guarantees that the only filesystem inconsistencies on unclean shutdown are leaked blocks and inodes. To resolve this you can run a background fsck or you can ignore it until you start to run out of space. We also could’ve written a mark and sweep garbage collector but never did. Ultimately, the bgfsck is too expensive and people did not like the uncertainty of not having run fsck. To resolve these issues, I have added a small journal to softupdates. However, I only have to journal block allocation and free, and inode link count changes since softdep guarantees the rest. My journal records are each only 32bytes which is incredibly compact compared to any other journaling solution. We still get the great concurrency and ability to ignore writes which have been canceled by new operations. But now we have recovery time that is around 2 seconds per megabyte of journal in-use. That’s 32,768 blocks allocated, files created, links added, etc. per megabyte of journal.

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