Purest yet liver-like cells generated from induced pluripotent stem cellsAugust 29, 2016
A research team including developmental biologist Stephen A. Duncan, D. Phil., SmartStateTM Chair of Regenerative Medicine at the Medical University of South Carolina (MUSC), has found a better way to purify liver cells made from induced pluripotent stem cells (iPSCs). Their efforts, published August 25, 2016 in Stem Cell Reports, will aid studies of liver disease for the National Heart, Lung, and Blood Institute (NHLBI)'s $80 million Next Generation Genetic Association Studies (Next Gen) Program. The University of Minnesota (Minneapolis) and the Medical College of Wisconsin (Milwaukee) contributed to the study.
This new methodology could facilitate progress toward an important clinical goal: the treatment of patients with disease-causing mutations in their livers by transplant of unmutated liver cells derived from their own stem cells. Previous attempts to generate liver-like cells from stem cells have yielded heterogeneous cell populations that bear little resemblance to diseased livers in patients.
NHLBI's Next Gen was created to bank stem cell lines sourced from patients in genome-wide association studies (GWAS). The goal of the NHLBI Next Gen Lipid Conditions sub-section--a collaborative effort between Duncan and Daniel J. Rader, M.D., and Edward E. Morrisey, Ph.D., both at the University of Pennsylvania--is to help determine the genetic sources of heart, lung, or blood conditions that also encompass the liver. These GWAS studies map the genomes in hundreds of people as a way to look for genetic mutation patterns that differ from the genomes of healthy individuals.
A GWAS study becomes more powerful--more likely to find the correct genetic mutations that cause a disease--as more genomes are mapped. Once a panel of suspected mutations is built, stem cells from these individuals can be "pushed" in culture dishes to differentiate into any of the body's cells, as for example liver-, heart-, or vascular-like cells. The cells can be screened in high-throughput formats (i.e., cells are expanded and cultured in many dishes) to learn more about the mutations and to test panels of drugs that might ultimately help treat patients harboring a disease.
The problem arises during the "pushing." For example, iPSCs stubbornly refuse to mature uniformly into liver-like cells when fed growth factors. Traditionally, antibodies have been used to recognize features of maturity on the surfaces of cells and purify cells that are alike. This approach has been crucial to stem cell research, but available antibodies that recognize mature liver cells are few and tend to recognize many different kinds of cells. The many types of cells in mixed populations have diverse characteristics that can obscure underlying disease-causing genetic variations, which tend to be subtle.
"Without having a pure population of liver cells, it was incredibly difficult to pick up these relatively subtle differences caused by the mutations, but differences that are important in the life of an individual," said Duncan.
Instead of relying on antibodies, Duncan and his crew embraced a new technology called chemoproteomic cell surface capture (CSC) technology. True to its name, CSC technology allowed the group to map the proteins on the surface of liver cells that were most highly produced during the final stages of differentiation of stem cells into liver cells. The most abundant protein was targeted with an antibody labeled with a fluorescent marker and used to sort the mature liver cells from the rest.
The procedure was highly successful: the team had a population of highly pure, homogeneous, and mature liver-like cells. Labeled cells had far more similar traits of mature hepatocytes than unlabeled cells. Pluripotent stem cells that had not differentiated were excluded from the group of labeled cells.
"That's important," said Duncan. "If you're wanting to transplant cells into somebody that has liver disease, you really don't want to be transplanting pluripotent cells because pluripotent cells form tumors called teratocarcinomas."
Duncan cautions that transplantation of iPSC-derived liver cells is not yet ready for translation to the clinic. But the technology for sorting homogeneous liver cells can be used now to successfully and accurately model and study disease in the cell culture dish.
"We think that by being able to generate pure populations, it will get rid of the variability, and therefore really help us combine with GWAS studies to identify allelic variations that are causative of a disease, at least in the liver," said Duncan.
Founded in 1824 in Charleston, The Medical University of South Carolina is the oldest medical school in the South. Today, MUSC continues the tradition of excellence in education, research, and patient care. MUSC educates and trains more than 3,000 students and residents, and has nearly 13,000 employees, including approximately 1,500 faculty members. As the largest non-federal employer in Charleston, the university and its affiliates have collective annual budgets in excess of $2.2 billion. MUSC operates a 750-bed medical center, which includes a nationally recognized Children's Hospital, the Ashley River Tower (cardiovascular, digestive disease, and surgical oncology), Hollings Cancer Center (a National Cancer Institute designated center) Level I Trauma Center, and Institute of Psychiatry. For more information on academic information or clinical services, visit musc.edu. For more information on hospital patient services, visit muschealth.org.
Medical University of South Carolina
Related Stem Cells Articles:
Researchers have identified a protein that must be present in order for mammary stem cells to perform their normal functions.
Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body.
Researchers have developed a new approach for growing and studying cells they hope one day will lead to curing lung diseases such as cystic fibrosis through 'personalized medicine.'
Generating mature and viable heart muscle cells from human or other animal stem cells has proven difficult for biologists.
DNA mutations in bone cells that support blood development can drive leukemia formation in nearby blood stem cells.
With age, the chromosomes of our cardiac stem cells compress as they move into a state of safe, semiretirement.
A team of researchers from the Medical University of South Carolina and elsewhere has found a better way to purify liver cells made from induced pluripotent stem cells.
International stem cell scientists, co-led in Canada by Dr. John Dick and in the Netherlands by Dr.
Signaling a potential new approach to treating diabetes, researchers at Washington University School of Medicine in St.
In a new Cell Reports paper, a team led by John P.
Related Stem Cells Reading:
Stem Cell Therapy: A Rising Tide: How Stem Cells Are Disrupting Medicine and Transforming Lives
by Neil H Riordan (Author)
Stem cells are the repair cells of your body. When there aren’t enough of them, or they aren’t working properly, chronic diseases can manifest and persist. From industry leaders, sport stars, and Hollywood icons to thousands of everyday, ordinary people, stem cell therapy has helped when standard medicine failed. Many of them had lost hope. These are their stories.
Neil H Riordan, author of MSC: Clinical Evidence Leading Medicine’s Next Frontier, the definitive textbook on clinical stem cell therapy, brings you an easy-to-read book about how and why stem cells work,... View Details
Stem Cell Revolution: Discover 26 Disruptive Technological Advances to Stem Cell Activation
by Joseph Christiano (Author)
Addressing chronic back pain, diabetes, joint replacements, osteoarthritis, neurological issues, and more, Joseph “Dr. Joe” Christiano reveals
how this cutting-edge therapy can rapidly replace damaged cells in the body with no side effects or allergic reactions.
If you have been disappointed by ineffective treatments, the answer to improving your health may be in your stem cells. Dr. Joe explains
how adult stem cell therapy and activators are two of the new technologies in regenerative medicine that will be game changers in medical history.
... View Details
Stem Cells For Dummies
by Lawrence S.B. Goldstein (Author), Meg Schneider (Author)
The first authoritative yet accessible guide to this controversial topic
Stem Cell Research For Dummies offers a balanced, plain-English look at this politically charged topic, cutting away the hype and presenting the facts clearly for you, free from debate. It explains what stem cells are and what they do, the legalities of harvesting them and using them in research, the latest research findings from the U.S. and abroad, and the prospects for medical stem cell therapies in the short and long term.Explains the differences between adult stem cells and embryonic/umbilical... View Details
Stem Cells: An Insider's Guide
by Paul Knoepfler (Author)
Stem Cells: An Insider's Guide is an exciting new book that takes readers inside the world of stem cells guided by international stem cell expert, Dr. Paul Knoepfler. Stem cells are catalyzing a revolution in medicine. The book also tackles the exciting and hotly debated area of stem cell treatments that are capturing the public's imagination. In the future they may also transform how we age and reproduce. However, there are serious risks and ethical challenges, too. The author's goal with this insider's guide is to give readers the information needed to distinguish between the... View Details
Stem Cells: Promise and Reality
by Lygia V Pereira (Author)
Stem Cells: Promises and Reality will tell you everything you have always wanted to know about stem cells, but could not understand the field from elsewhere. Stem cells are the great therapeutic promise of the century, and this evolving field of research and medicine brings with it many legal, ethical and psychological issues that must be discussed by society as a whole. Written so as to be accessible to general readers as well as specialists, this book explains what stem cells are, and the different aspects of stem cell research and applications. The book will enable the reader to understand... View Details
Stem Cells Are Everywhere
by Irv Weissman MD (Author)
An engaging introduction to stem cells for young scientists
How do you heal when you cut your skin or break a bone? How does your body keep making new blood or brain cells, or even second teeth? How does a plant keep growing larger? The answers lie in stem cells, which are found in every growing plant and animal. Keeping the subject simple enough for young readers, a pioneer of stem cell research explains cells, tissues, normal growth, what can go wrong, and how to fix it. View Details
The Stem Cell Revolution
by Mark Berman MD (Author), Elliot Lander MD (Contributor)
The book describes the journey into the growing arena of clinical stem cell therapy by highlighting not only the road that brought a team of physicians together but also real stories from a number of their patients that were given their health back through the magic of stem cell therapy. Your fat is loaded with stem cells that can be used now to treat and reverse a large number of inflammatory and degenerative conditions. Most people have no idea that these magical cells actually exist right within our bodies. They think that they must wait until Big Pharma or a university PhD manufactures... View Details
Stem Cells: A Short Course
by Rob Burgess (Author)
Stem Cells: A Short Course is a comprehensive text for students delving into the rapidly evolving discipline of stem cell research. Comprised of eight chapters, the text addresses all of the major facets and disciplines related to stem cell biology and research. A brief history of stem cell research serves as an introduction, followed by coverage of stem cell fundamentals; chapters then explore embryonic and fetal amniotic stem cells, adult stem cells, nuclear reprogramming, and cancer stem cells. The book concludes with chapters on stem cell applications, including the role of stem... View Details
Stem Cells: A Very Short Introduction
by Jonathan Slack (Author)
Embryonic stem cells have been hot-button topics in recent years, generating intense public interest as well as much confusion and misinformation. In this Very Short Introduction, leading authority Jonathan Slack offers a clear and informative overview of stem cells--what they are, what scientists do with them, what stem cell therapies are available today, and how they might be used in the future. Slack explains the difference between embryonic stem cells, which exist only in laboratory cultures, and tissue-specific stem cells, which exist in our bodies, and he discusses how... View Details
Essentials of Stem Cell Biology, Third Edition
by Robert Lanza (Editor), Anthony Atala (Editor)
First developed as an accessible abridgement of the successful Handbook of Stem Cells, Essentials of Stem Cell Biology serves the needs of the evolving population of scientists, researchers, practitioners, and students embracing the latest advances in stem cells. Representing the combined effort of 7 editors and more than 200 scholars and scientists whose pioneering work has defined our understanding of stem cells, this book combines the prerequisites for a general understanding of adult and embryonic stem cells with a presentation by the world's experts of the latest... View Details