Liver Cells Grown From Patients’ Skin Cells; Treatment Of Liver Diseases Possible
These are liver cells generated from skin that are shown to make human liver proteins Albumin in green and HNF4 in red. (Credit: Medical College of Wisconsin)
From ScienceDaily.com
Scientists at The Medical College of Wisconsin in Milwaukee have successfully produced liver cells from patients’ skin cells opening the possibility of treating a wide range of diseases that affect liver function.
The study, published in the journal Hepatology, was led by Stephen A. Duncan, D. Phil., Marcus Professor in Human and Molecular Genetics, and professor of cell biology, neurobiology and anatomy, along with postdoctoral fellow Karim Si-Tayeb, Ph.D., and graduate student Ms. Fallon Noto.
“This is a crucial step forward towards developing therapies that can potentially replace the need for scarce liver transplants, currently the only treatment for most advanced liver disease,” says Dr. Duncan.
Liver disease is the fourth leading cause of death among middle aged adults in the United States. Loss of liver function can be caused by several factors, including genetic mutations, infections with hepatitis viruses, by excessive alcohol consumption, or chronic use of some prescription drugs. When liver function goes awry it can result in a wide variety of disorders including diabetes and atherosclerosis and in many cases is fatal.
The Medical College research team generated patient–specific liver cells by first repeating the work of James Thomson and colleagues at University of Wisconsin-Madison who showed that skin cells can be reprogrammed to become cells that resemble embryonic stem cells. They then tricked the skin–derived pluripotent stem cells into forming liver cells by mimicking the normal processes through which liver cells are made during embryonic development. Pluripotent stem cells are so named because of their capacity to develop into any one of eh more than 200 cell types in the human body.
At the end of this process, the researchers found that they were able to very easily produce large numbers of relatively pure liver cells in laboratory culture dishes. “We were excited to discover that the liver cells produced from human skin cells were able to perform many of the activities associated with healthy adult liver function and that the cells could be injected into mouse livers where they integrated and were capable of making human liver proteins,” says Dr. Duncan.
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Trio Of Signals Converge To Induce Liver And Pancreas Cell Development In The Embryo
From ScienceDaily.com
Understanding the molecular signals that guide early cells in the embryo to develop into different organs provides insight into ways that tissues regenerate and how stem cells can be used for new therapies. With regenerated cells, researchers hope to one day fill the acute shortage in pancreatic and liver tissue available for transplantation in cases of type I diabetes and acute liver failure.
Previous studies on pancreas and liver development have focused on individual molecular signals that induce these tissues to mature from a common precursor cell population. In a new study, published this week in Science, researchers investigated a trio of cell-signaling pathways that work simultaneously, converging to direct pancreas and liver progenitor cells to mature into their final state. They looked at how BMP, TGF-beta, and FGF signaling pathways turn on genes that guide cells to ultimately become pancreas or liver tissue.
The structure of the cell-signaling network provides insight into the basis of tissue development and how it can be manipulated to facilitate pancreas and liver-cell regeneration and development from embryonic stem cells.
“For my entire scientific life, I’ve been intrigued by how cells early in development make ‘decisions’ to turn on one genetic program and exclude others,” says Kenneth S. Zaret, PhD, Professor of Cell and Developmental Biology and Associate Director at the Institute for Regenerative Medicine at the University of Pennsylvania School of Medicine.
The work was conducted while Zaret and co-author Ewa Wandzioch, PhD, Research Associate in the Department of Cell and Developmental Biology, were at the Fox Chase Cancer Center in Philadelphia.
How the developing embryo starts to apportion different functions to different cell types is a key question for developmental biology and regenerative medicine.
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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.
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