November 21st, 2014
Tissue engineering is an extraordinary research field aim to engineer entire new organs from single cells. Not only would it resolve the problem of organs availability, but it would also annihilate the risk of graft rejection from the immune system.
The complexity of such process arise not only from a complex single organ cellular diversity, but also from the necessity of having the right cellular organization and complete networks of blood vessels to keep these cells alive. This complexity is particularly true for the heart, which has intricate networks of capillaries. Therefore, regenerative-medicine researchers are trying to reuse what biology has already created.
The technique consist of removing all cells from a heart, which doesn’t have to be human, to end up with protein scaffold that can be repopulate with stem cells immunologically matched to the patient.
For the decellularization process, detergent is pumped into the heart for about a week to strip away lipids, DNA, soluble proteins, sugars and almost all the other cellular material, leaving only a pale mesh of collagen, laminins and other structural proteins. This technique permit to remove cell-surface molecules that can lead to rejection by the recipient’s immune system, while keeping the vital proteins and growth factors that will tell the newly introduced cells where to adhere and how to behave.
For the recellularization, most researchers in the field use a mixture of two or more cell types, such as endothelial precursor cells to line blood vessels, and muscle progenitors to seed the walls of the chambers. These cells have been derive from induced pluripotent stem cells (adult cells reprogrammed to an embryonic-stem-cell-like state using growth factors), because these can be taken from a patient to make immunologically matched tissues.
Researching teams have implanted these reconstructed hearts into rats, generally in the neck, in the abdomen or alongside the animal’s own heart. But although the researchers can feed the organs with blood and get them to beat for a while, none of the hearts has been able to support the blood-pumping function. The researchers need to show that a heart has much higher ability to function before they can transplant it into an animal bigger than a rat.
Although there is doubt in the scientific community on the eventual successful creation of hearts from single cells that are functional and reliable, this technique should have important applications. This could in a few years enable the bioengineering of parts of the heart, such has valves, that may last longer than actual mechanical or dead-tissue parts because of their potential to grow with a patient and repair themselves.
Image credit: NIK SPENCER/NATURE
Maher B (2013). Tissue engineering: How to build a heart. Nature, 499 (7456), 20-2 PMID: 23823778
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