26 December 2016

Liver organoids from a 3D printer

The data of preclinical studies of the liver created by 3D bioprinting were obtained

Anatoly Alizar, Geektimes

NovoGen bioprinter, which is used to print the liver

Organovo presented data from preclinical studies of artificial human liver created by organic 3D printing (Organovo Presents First Preclinical Data on 3D Bioprinted Human Liver Tissues at TERMIS-Americas Meeting). The results were announced at the TERMIS-Americas conference, which was held on December 11-14, 2016 in San Diego. For the first time, tests in practice showed the survival of artificial human tissue and its stable functioning in the mouse body. Evidence of stable formation of blood vessels in the liver has been obtained. The study showed the most important thing: human proteins are actually produced in the artificial liver and key enzymes of human metabolism are manifested.

This is an important step towards the start of full-fledged clinical trials, and then commercial 3D printing of organs in unlimited quantities – for installation to those in need.

During the tests, fragments of human liver tissue were implanted into the liver of a white NOD/SCID mutant mouse with immunodeficiency, specially bred for such experiments. The tissue consists of human hepatocytes (liver parenchyma cells) and individual non-parenchymal cells. The functioning of 3D-printed human liver tissue was observed by human albumin, alpha-1-antitrypsin and fibrinogen circulating in mouse blood for 7-28 days after implantation. Histological evaluation of the implanted therapeutic tissue showed the preservation of cellular organization for 28 days after implantation with a healthy manifestation of key human metabolic enzymes that are associated with congenital metabolic defects, such as fumarylacetoacetate hydrolase (FAH) deficiency and ornithine transcarbamylase (OTC) deficiency. The tissues of the human liver behaved exactly as they should. Throughout the entire period of preclinical tests, liver tissue remained intact and was well received by the animal body.

The results of preclinical studies support Organovo's plan to 3D-print an artificial liver for therapeutic use.

Artificial liver will be an important achievement of modern biomedicine and 3D printing. First of all, it will help people suffering from congenital metabolic diseases listed above and acute chronic liver failure. 

The liver is one of the most scarce organs for transplantation. Dozens die every day due to liver failure, because they did not get an organ for transplantation. 3D printing can forget about this organ shortage forever. It is not surprising that Organovo liver bioprinting was included in the list of the 10 most important discoveries of 2016 according to The Scientist magazine.

Growing a human liver organoid from IPSC (from an article in Nature)

"Our preclinical data show rapid vascularization [formation of new blood vessels] and tissue engraftment," says Dr. Eric Michael David, Chief Strategic Officer and Executive Vice President for preclinical Development at Organovo, "and evidence of the functioning and longevity of the liver printed by 3D bioprinting for several years weeks. The most important thing is that we have received evidence of stable production of human proteins in the liver and the manifestation of key enzymes of human metabolism."

Within three to five years, Organovo is going to complete all the necessary tests and submit an Investigational New Drug (“IND”) application for a new drug to the U.S. Food and Drug Administration (FDA). After the approval of the FDA application, nothing will prevent the drug from being brought to the US market, and soon to other countries. 

To patent human liver cells created by this method, Organovo has entered into a licensing agreement with Uniquest. Probably, Organovo itself will concentrate on scientific research and will receive royalties, and the bioengineers of Uniquest will grow tissue for sale.
Organovo has also started signing distribution agreements in advance with companies that will sell printed liver in other countries. For example, in Japan, Cosmo Bio will become the official distributor. The seller of Organovo cookies in Russia has not yet been determined.

For more information about Organovo's artificial liver, see also the scientific article Kidney organoids from human iPS cells contain multiple lines and model human nephrogenesis, published in the journal Nature.

Portal "Eternal youth" http://vechnayamolodost.ru  26.12.2016

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