Tag Archives: liver

Scientists create functional liver cells from stem cells

Major implications for liver biology and drug discovery

THE HEBREW UNIVERSITY OF JERUSALEM

Image: This image shows stem cell-derived hepatocytes emerging. Photo Credit: Yaakov Nahmias/Hebrew University

The liver plays a critical role in human metabolism. As the gatekeeper of the digestive track, this massive organ is responsible for drug breakdown and is therefore the first to be injured due to overdose or misuse. Evaluating this drug-induced liver injury is a critical part of pharmaceutical drug discovery and must be carried out on human liver cells. Regretfully, human liver cells, called hepatocytes, are in scarce supply as they can only be isolated from donated organs.

Now, in research published on the cover of the July edition of Hepatology, scientists from the Hebrew University of Jerusalem’s Alexander Grass Center for Bioengineering report that they produced large amounts of functional liver cells from human embryonic and genetic engineered stem cells.

Early Results Show Promise for Stem Cells in Treating Chronic Liver Failure

Stem cell transfusions may someday replace the need for transplants in patients who suffer from liver failure caused by hepatitis B, according to a new study coming out of Beijing. . The results are published in the October issue of STEM CELLS Translational Medicine. Worldwide more than 500,000 people die each year from this condition.

“In China, hepatitis B virus (HBV) infection accounts for the highest proportion of liver failure cases. While liver transplantation is considered the standard treatment, it has several drawbacks including a limited number of donors, long waiting lists, high cost and multiple complications. Our study shows that mesenchymal stem cell (MSCs) transfusions might be a good, safe alternative,” said Fu-Sheng Wang, Ph.D., M.D., the study’s lead author and director of the Research Center for Biological Therapy (RCBT) in Beijing.

Wang along with RCBT colleague, Drs. Ming Shi and Zheng Zhang of the Research Center for Biological Therapy, The Institute of Translational Hepatology led the group of physician-scientists from the centers and Beijing 302 Hospital who conducted the study.

MSC transfusions had already been shown to improve liver function in patients with end-stage liver diseases. This time, the researchers wanted to gauge the safety and initial efficacy of treating acute-on-chronic liver failure (ACLF) with MSCs. The American Association for the Study of Liver Diseases and the European Association for the Study of the Liver define ACLF as an “acute deterioration of pre-existing chronic liver disease usually related to a precipitating event and associated with increased mortality at three months due to multisystem organ failure.” The short-term mortality rate for this condition is more than 50 percent.

MSCs have self-renewing abilities and the potential to differentiate into various types of cells. More importantly, they can interact with immune cells and cause the immune system to adjust to the desired level.

Of the 43 patients in this pilot study — each of whom had liver failure resulting from chronic HBV infection — 24 were treated with MSCs taken from donated umbilical cords and 19 were treated with saline as the control group. All received conventional therapy as well. The liver function, adverse events and survival rates were then evaluated during the 48-week or 72-week follow-up period.

Along with increased survival rates, the patients’ liver function improved and platelet count increased. No significant side effects were observed throughout the treatment and follow-up period.

“While the results are preliminary and this pilot study includes a small number of patients, MSC transfusions appear to be safe and may serve as a novel therapeutic approach for HBV-associated ACLF patients,” Dr. Shi said.

“The study also highlights several key issues that will need to be considered in the design of future clinical studies, such as the optimal type of stem cells that will be infused, the minimum effective number of the cells and the best route of administration,” Dr. Wang added.

“These results are certainly promising and the strategy merits additional study, especially considering the shortage of donor organs”  said Anthony Atala, MD, Editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

Wisconsin team starts with skin, derives liver cells

By Mark Johnson of the Journal Sentinel, JSOnline.com

Just after 5 p.m. doors rattle shut and feet begin to shuffle past the narrow lab where Karim Si-Tayeb sits hunched over a microscope, all but invisible to the scientists leaving the Medical College of Wisconsin.

Si-Tayeb has already worked eight hours and will work five more, eyes locked on the living cells in his care. Under the microscope, their tiny colonies resemble constellations of tightly packed stars. They carry his ambition.

“A few months ago I was working and it struck me how incredibly cool this is,” he said, sliding a dish of unusual cells under the microscope, cells he had scientifically altered. “This revolution is occurring, and you are part of it.”

Early this year the 32-year-old postdoctoral student from France joined a biomedical revolution by reprogramming human skin cells back to their embryonic origin, just as James Thomson in Madison and Shinya Yamanaka in Japan did when they made headlines in November 2007. Now Si-Tayeb and his supervisor, Stephen A. Duncan, a Medical College professor, were engaged in the next great race.

In 2008, scientists began trying to turn the new reprogrammed cells into all of the building blocks doctors might use to treat a multitude of diseases. Cardiac cells to repair a damaged heart. Insulin-producing cells to help diabetics. Photoreceptor cells to restore lost vision.

The work would be crucial if stem cells were to fulfill their promise and begin a new wave of medicine.

Duncan and Si-Tayeb were tryingto become the first scientists to use the new technology to make liver cells. They hoped the liver cells would someday help patients with a relatively rare form of inherited diabetes called MODY (mature onset diabetes of the young). Reprogrammed cells from MODY patients could provide a microscopic view of the disease as it progresses and give scientists a target for drug testing.

The stakes were high for Si-Tayeb, still early in his career and dreaming of a big scientific paper with his name on it.

At night, Duncan lay awake worrying. When he did drift off to sleep, sometimes he dreamed of work, the anxiety flowing through him, waking him with a jolt. What if their analysis was flawed? What if while they worried and double-checked, another scientist published the same discovery? As much as he wanted to be first, Duncan vowed no corners would be cut.

“Rigor in science is everything,” he said. “Without it you have nothing.”

Their dilemma was now the dilemma of many in the field, an illustration of how a major advance alters the scientific landscape.

Click link above for complete article.