New method to create bioartificial organs

Scientists unveil new method to create bioartificial organs
November 2, 2010 Spanish scientists on Tuesday presented a new technique to create bioartifical organs for transplant using stem cells which they said will vastly reduce the risk of rejection of the donated organ.

The technique involves "stripping" a donated heart, liver or other organ which is deemed unsuitable for donation of their cells, leaving just a "scaffold", Francisco Fernandez-Aviles, chief cardiologist at Madrid's Gregorio Maranon hospital told a news conference.

Stem cells from the patient are then applied to this framework to re-grow the organ which will share their DNA, thus making it more acceptable to their body.

Doctors will be able to carry out transplants involving organs that have been re-generated using this technique in five years time at the earliest, said Fernandez-Aviles.

"This will put an end to two problems: the lack of donors or organs suitable for transplant and the rejection of transplanted organs by the patient," he said.

The hospital has eight heart "scaffolds" ready for use with this technique and it hopes to partially re-grow one heart using stem cells by the end of the year.

Science Minister Cristina Garmendia said the hospital "has the first lab in the world dedicated to producing bioartifical organs for transplant using adult stem cells."

Three years ago the hospital became the first in the world to use stem cells from a patient's fat tissue, extracted through liposuction, to treat his heart.

Massive investment has been directed into stem-cell research, driven by hopes that immature, pre-cursor cells can be prompted into becoming specific adult cells for the heart, brain and so on.

Spain has become a world leader in organ donation since it set up a network of transplant coordinators in 1989 at all hospitals in the country which closely monitor emergency wards to identify potential donors.

When they learn of a death, they tactfully talk to the grieving families to get permission to use the organs to help save the lives of others.

Only about 15 percent of families approached in Spain refused consent for organ donation, a huge drop from the 40 percent who refused in the 1980s before the system was set up
c) 2010 AFP
http://www.physorg.com/news/2010-11-scientists-unveil-method-bioartificial.html

AASLD/ELAD® Bioartificial Liver/3yr Follow Up Confirm Saftey&Survival Benefit

Three-Year Follow-Up Data Confirm Safety and Survival Benefit in Chinese Liver Failure Patients Treated With ELAD® Bioartificial Liver

Poster presentation scheduled at AASLD November 2nd

Vital Therapies, Inc.

/PRNewswire/ -- Vital Therapies, Inc., (VTI) today announced that a poster is being presented at the American Association for the Study of Liver Diseases (AASLD) meeting in Boston on Tuesday, November 2nd. It confirms that previously reported findings of improved transplant free survival (TFS) in Chinese subjects with acute-on-chronic liver failure (ACLF) treated with the ELAD® bioartificial liver support system are maintained for up to three years.

The poster is titled "3-year follow-up of acute-on-chronic liver failure (ACLF) subjects in randomized, controlled, multicenter trial of ELAD® bioartificial liver support system in 49 Chinese subjects reveals significant transplant-free survival (TFS) benefit." It is being presented by Dr. Michael Millis, Professor of Surgery, University of Chicago, and is coauthored by Drs. Zhongping Duan and Jing Zhang, Beijing You'an Hospital, and Shaojie Xin and Shaoli You, 302 Military Hospital, Beijing.

Previously, it was reported that 84-day follow-up of ACLF subjects enrolled at two liver treatment centers in China showed statistically significant improvements in TFS for ELAD treatment compared with standard of care (SOC). At least three years following enrollment, survivors were consented and underwent a cancer screen and physical exam in accord with a questionnaire.

Of 49 subjects enrolled, 84-day TFS was 21/32 (65.6%) in the ELAD group vs. 7/17 (41.1%) in controls. Three-year TFS was 14/32 (43.8%) in the ELAD group vs. 3/12 (25%) in controls. Of 84-day survivors, 2/21 (9.5%) ELAD and 2/7 (28.6%) controls died, 1/21 (4.8%) ELAD and 0/7 controls were transplanted and 4/21 (19.0%) ELAD and 2/7 (28.6%) controls were lost to follow-up. Survival analysis reveals a statistically significant improvement in TFS (p=0.045, log-rank analysis) for the ELAD treated subjects compared with SOC. Median survival of controls was 37 days, whereas median survival of ELAD treated subjects was at least 3 years. There was no evidence of tumor development in either group.

Dr. Millis commented, "This is the first time that a long term survival benefit has been demonstrated in subjects who recovered following treatment with ELAD. It is highly encouraging to note that those subjects that survive in the short term are able to go on to extended survival without any apparent increase in mortality or morbidity compared with subjects administered standard of care."

Dr. Duan, who served as a principal investigator for the study, commented, "China has about 95 million HBV carriers and chronic hepatitis B patients, and 38 million hepatitis C patients. It is estimated that 0.1%-0.5% of these patients will experience severe hepatitis due to acute hepatocellular necrosis or hypofunction, which results in hepatic insufficiency and hepatic failure. Mortality from this condition still remains around 50%-70% even with comprehensive internal medicine treatment, leading to as many as 400,000 deaths per year in China from acute liver failure. When approved for commercial sale in China, ELAD will be the first bioartificial liver support system proven to improve survival in this population."

In order to confirm these findings from China, VTI is conducting the SILVER (Stabilization In LiVER Failure) trial in the United States, Europe and Saudi Arabia which has achieved 50% of its targeted enrollment. Should this study yield positive findings, these results, along with data from other studies, will form the basis of regulatory filings for future marketing authorization.

About ELAD and the SILVER Trial

The SILVER protocol enrolls subjects with chronic liver disease who have been hospitalized as a result of an event, such as an infection or an episode of bleeding, which has caused deterioration of their liver function (acute-on-chronic liver failure, ACLF). The trial is designed to explore whether the use of ELAD in this setting can prevent continued deterioration of liver function, called progression, and thus improve survival. The trial design uses a well-established measure of liver function called the MELD score to define the status of liver function. Treatment with ELAD, along with standard of care, is compared with standard of care alone. The time to either death or deterioration of liver function by a pre-specified amount is measured. It is postulated that the use of ELAD may extend the time to progression and improve survival in this rapidly progressing patient population.

ELAD is a biologic liver support system using a proprietary line of allogeneic human liver cells refined by several leading cell experts. The cells are stable, immortal, can be grown in unlimited quantities and retain their hepatocyte (liver cell) characteristics. About one pound of cells is used for each treatment. The cells are grown in specially designed cartridges at VTI's cell culture facility and used to treat the patient for up to ten days.

About Vital Therapies, Inc.

Vital Therapies, Inc. (VTI) is based in San Diego, California, with a wholly owned subsidiary in Beijing, China. VTI is developing the first human liver cell-based Extracorporeal Liver Assist System (ELAD). ELAD could provide support for patients with severe liver failure by processing toxins and also synthesizing proteins and metabolites that are key products of normal human liver function. ELAD is in investigational clinical trials and VTI completed a pivotal trial and filed for market approval in China in September 2007. For additional information visit http://www.vitaltherapies.com/ or contact Terry Winters, PhD, CEO, Vital Therapies at +1 858 673 6840.

ELAD is a trademark of Vital Therapies, Inc.

SOURCE Vital Therapies, Inc.
http://www.kansascity.com/2010/10/13/2311093/three-year-follow-up-data-confirm.html

AASLD/Creating Functional Hepatic Tissue in a Bioengineered Human Liver

PR Newswire

BOSTON, Oct. 30

BOSTON, Oct. 30 /PRNewswire/ -- Researchers at Wake Forest University Baptist Medical Center's Institute for Regenerative Medicine demonstrated the generation of a bioengineered human liver organoid using a liver bioscaffold made from an intact liver extracellular matrix, and filled (seeded) with primary human liver progenitor and endothelial cells.

The ability to generate a liver scaffold and preserve its vascular network had been demonstrated previously. These studies showed the possibility of seeding these bioscaffolds with liver cells from animals, but the possibility of generating functional human hepatic tissue was still in question.

The current study demonstrated that human liver cells can be seeded through the portal vein of the liver bioscaffold, and can be maintained in a specialized bioreactor with constant culture medium perfusion up to one week. Progressive human liver tissue formation was documented, as well as liver-associated functions. Widespread cell proliferation inside the bioengineered liver tissue with low cell apoptosis was also observed.

According to Pedro Baptista, PharmD, PhD, "These studies provide the basis to begin transplantation of bioengineered livers in small animal models. We believe that this functional hepatic tissue, once transplanted, will maintain and further gain function as it progressively grows and develops in vivo. Also, the exclusive use of human cells opens new horizons for drug testing and toxicology studies. This will more closely mimic drug metabolism in the human liver, which animal models can, at times, be extremely difficult to predict."

"This technology may provide a new approach for liver bioengineering, enabling the use of organ scaffolds with human cells to produce functional human liver tissue," said Dr. Baptista.

The researcher hails this as a new approach to whole organ liver bioengineering that might prove to be critical for drug discovery and treatment of liver disease. "This laboratory-generated hepatic tissue offers great potential as a drug discovery and toxicology testing platform. Moreover, we believe that further translation into larger animal species opens the door for the generation of transplantable bioengineered human livers that can help patients with end-stage chronic liver disease who are waiting for a donor."

Abstract title:
The Use of Whole Organ Decellularization for the Bioengineering of a Human Vascularized Liver

About the AASLD
AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in Boston, Massachusetts, October 29-November 2, will bring together more than 7,500 researchers from 55 countries.

A pressroom will be available from October 30 at the annual meeting. For copies of abstracts and press releases, or to arrange for pre-conference research interviews contact Gregory Bologna at 703-299-9766. To pre-register, call Ann Haran at 703-299-9766.

Press releases and all abstracts are available online at www.aasld.org .

Media Contact: Gregory Bologna

703/299-9766

gbologna@aasld.org

Press Room: October 30 – November 2, 2010

Hynes Convention Center, Room 208

Telephone: 617-954-3106

Researchers: Pedro Baptista, PharmD, PhD; Shay Soker, PhD

Email: pbaptist@wfubmc.edu; ssoker@wfubmc.edu

Phone: 336-713-1325

This release was issued through The Xpress Press News Service, merging e-mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit http://www.XpressPress.com .

SOURCE American Association for the Study of Liver Diseases (AASLD)

Read more: http://www.digitaljournal.com/pr/149299#ixzz13qhE7qYS