Update: Global Medical Research.org now has 182 top medical researchers and computer scientists from around the world as part of our community. Please visit our linkedin group for individual member research interests and collaboration opportunities. Kary Mullis' next-gen cure for killer infect...
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Update: Global Medical Research.org now has 182 top medical researchers and computer scientists from around the world as part of our community. Please visit our linkedin group for individual member research interests and collaboration opportunities.
Kary Mullis won the Nobel Prize in Chemistry for developing a way to copy a strand of DNA. (His technique, called PCR, jump-started the 1990s' biorevolution.) He's known for his wide-ranging interests -- and strong opinions.
In the early 1980s, Kary Mullis developed the polymerase chain reaction, an elegant way to make copies of a DNA strand using the enzyme polymerase and some basic DNA "building blocks." The process opened the door to more in-depth study of DNA -- like the Human Genome Project. Mullis shared the 1993 Nobel Prize in Chemistry for developing this technique.
As he tells it, after winning the Nobel Prize, his next career move was to learn how to surf. It's typical of Mullis, whose scientific method is to get deeply curious about a topic, work it out from first principles, and then imagine the next giant leap forward. As he puts it in his Nobel autobiography, revised several times since 1993, "I read a lot, and think a lot, and I can talk about almost anything. Being a Nobel laureate is a license to be an expert in lots of things as long as you do your homework."
Most recently, he's been taking a hard look at immunity; a recent patent from his company Altermune describes the redirection of an existing immune response to a new pathogen.
In the fight against disease, defect and injury, Alan Russell has a novel argument: Why not engineer new tissue and organs to replace sick ones?
Text from TED.com
"Alan Russell is a professor of surgery -- and of chemical engineering. In crossing the two fields, he is expanding our palette of treatments for disease, injury and congenital defects. We can treat symptoms, he says, or we can replace our damaged parts with bioengineered tissue. As he puts it: "If newts can regenerate a lost limb, why can't we?"
The founding director of the McGowan Institute for Regenerative Medicine, at the University of Pittsburgh, Russell leads an ambitious biomedicine program that explores tissue engineering, stem cell research, biosurgery and artificial and biohybrid organs. Lately, they've started testing a new kind of heart pump, figured out that Botox can help with enlarged prostate, and identified human adipose cells as having the possibility to repair skeletal muscle. In his own Russell Lab, his team is studying antimicrobial surfaces and helping to develop a therapy to reduce scarring on muscle after injury.
He's also co-founder of Agentase, a company that makes an enzyme-based detector for chemical warfare agents.
"Russell's own research, a blend of biotech and chemical engineering, is directed at finding ways to put biological molecules into everyday materials."
A team of Harvard Stem Cell Institute (HSCI) researchers at Massachusetts General Hospital (MGH) and collaborators at Harvard’s School of Engineering and Applied Sciences (SEAS) has taken a giant step toward the possibility of using human stem cells to repair damaged hearts.
In a study scheduled for publication on Oct. 16 in the journal Science, the team lead by Kenneth Chien, M.D., PhD, an HSCI Principal Faculty member, reports using a mouse version of a human cardiac master stem cell to create a functioning strip of mouse heart muscle with technology developed by Kevin Kit Parker, the Thomas Dudley Cabot Associate Professor of Applied Science in Harvard's School of Engineering and Applied Sciences (SEAS) and a faculty member at the University's Wyss Institute for Biologically Inspired Engineering.
“This is the beginning of making heart parts for heart disease,” said Chien, the director of the MGH Cardiovascular Research Center and the Charles Addison and Elizabeth Ann Sanders Professor of Basic Science at Harvard Medical School (HMS).
This is an initial step in moving beyond heart stem cell biology towards a different level – finding a rare cardiomyogenic cell from embryonic stem cells that can proliferate on its own and could potentially be therapeutic. This work moves us closer to heart stem cell therapy,” Chien explained. “The beauty of the system our team has developed relates to the almost pure population of the exact cells, ventricular heart cells, which we’re trying to replace in a damaged heart, and then expanding and assembling them into a functioning strip of pure ventricular muscle. That has not been done to my knowledge.”
We’ve “been able to take these very rare populations of muscle progenitors that were isolated because we were able to color code the cells,” Chien explained. “We look for the cells that have a mixed color read out. We’ve been able to take those cells and put them one layer thick on something that is almost like Saran Wrap. When they contract, they flex the film. We have the pure cells; they can be expanded, and they can make fully functional strip of muscle.”
Kit Parker, whose lab developed the technology that produces a strip of muscle from the cardiac cells, said that "We try to develop technologies that are cell-agnostic; technologies that can work with Ken’s cardiac progenitors, or anyone else’s stem cells. These techniques are not limited to cardiac cells, or even to stem cells for that matter.”
The bioengineer explained that the best way to visualize the construction of the muscle strip might be to think of a “Fruit Roll-up,” but with cells taking the place of the pressed fruit.
Chien called the new findings “the latest in a chain of scientific discoveries that have come out of our lab here at Mass General and the Harvard Stem Cell Institute that have been a collaboration of physicians, scientists and bioengineers. For the first time we report the identification of a cell that could be viewed as perhaps an optimal cell type to promote cardiac muscle regeneration because the cells that we use come from embryonic stem cells and then have been induced to form an intact strip of functioning ventricular muscle.”
Chien said the work takes the most basic form of undifferentiated stem cell and directs its differentiation and development “to ventricular muscle – and that’s the type of muscle in the heart we’re trying to regenerate.”
“What we think we have right now are the exact cell types to do this type of repair,” said Ibrahim Domian, first author on the Science paper and a Harvard Medical School instructor in medicine. “One way or another we have to get to three dimensional muscle, which is made up of multiple layers of cells.
The amazing thing about these strips we have now is that they are generating the right amount of force, but as you want to generate more force, you have to increase the thickness of the strips, and they have to have their own blood supply. There are two ways you could do this; rely on tissue engineering to produce a strip like that, or find a way to use the natural architecture of the heart to regenerate the muscle. We’re now working hard in our lab and with Kit Parker, to see how we could produce the thicker strip.”
There are a number of approaches to solving the delivery problem, Chien said. One might be to incorporate the cells into a gel of some kind, which could be applied to the damaged muscle. Another might be to simply inject the cells into the damaged tissue, hoping that they would proliferate and create new muscle. In Chien’s view, novel technology for cell delivery will be required in either case.
Over the past two years Chien and his team have published a series of ‘leap-frogging’ studies, first making a discovery in mice, then replicating it in human embryonic stem cells; then taking the next step in mice, then moving onto to human cells. Next comes the attempt to actually repair cardiac damage in animals and then on to clinical studies in the next 5 years.
“In mice we’re in a position to attempt the repair right now,” Domian said. “We can cause a heart attack, and then look for ways to repair the tissue. The simplest way is to inject the cells into the tissue – we can do that right now in mouse. If that doesn’t work, we have to rely on other technologies.” But, he added, “this is direct proof of concept that a similar approach will work with human ES cells.”
“Now we’re actually in the core of the next level of challenges that face all of regenerative medicine,” said Chien. “In essence I think we’re moving quite quickly now from stem cell biology all the way through towards regenerative medicine.”
“This is an initial step in moving beyond heart stem cell biology towards a different level – finding a rare cardiomyogenic cell from embryonic stem cells that can proliferate on its own and could potentially be therapeutic. This work moves us closer to heart stem cell therapy,” Chien explained. “The beauty of the system our team has developed relates to the almost pure population of the exact cells, ventricular heart cells, which we’re trying to replace in a damaged heart, and then expanding and assembling them into a functioning strip of pure ventricular muscle. That has not been done to my knowledge.”
We’ve “been able to take these very rare populations of muscle progenitors that were isolated because we were able to color code the cells,” Chien explained. “We look for the cells that have a mixed color read out. We’ve been able to take those cells and put them one layer thick on something that is almost like Saran Wrap. When they contract, they flex the film. We have the pure cells; they can be expanded, and they can make fully functional strip of muscle.”
Kit Parker, whose lab developed the technology that produces a strip of muscle from the cardiac cells, said that "We try to develop technologies that are cell-agnostic; technologies that can work with Ken’s cardiac progenitors, or anyone else’s stem cells. These techniques are not limited to cardiac cells, or even to stem cells for that matter.”
The bioengineer explained that the best way to visualize the construction of the muscle strip might be to think of a “Fruit Roll-up,” but with cells taking the place of the pressed fruit.
Chien called the new findings “the latest in a chain of scientific discoveries that have come out of our lab here at Mass General and the Harvard Stem Cell Institute that have been a collaboration of physicians, scientists and bioengineers. For the first time we report the identification of a cell that could be viewed as perhaps an optimal cell type to promote cardiac muscle regeneration because the cells that we use come from embryonic stem cells and then have been induced to form an intact strip of functioning ventricular muscle.”
Chien said the work takes the most basic form of undifferentiated stem cell and directs its differentiation and development “to ventricular muscle – and that’s the type of muscle in the heart we’re trying to regenerate.”
“What we think we have right now are the exact cell types to do this type of repair,” said Ibrahim Domian, first author on the Science paper and a Harvard Medical School instructor in medicine. “One way or another we have to get to three dimensional muscle, which is made up of multiple layers of cells.
The amazing thing about these strips we have now is that they are generating the right amount of force, but as you want to generate more force, you have to increase the thickness of the strips, and they have to have their own blood supply. There are two ways you could do this; rely on tissue engineering to produce a strip like that, or find a way to use the natural architecture of the heart to regenerate the muscle. We’re now working hard in our lab and with Kit Parker, to see how we could produce the thicker strip.”
There are a number of approaches to solving the delivery problem, Chien said. One might be to incorporate the cells into a gel of some kind, which could be applied to the damaged muscle. Another might be to simply inject the cells into the damaged tissue, hoping that they would proliferate and create new muscle. In Chien’s view, novel technology for cell delivery will be required in either case.
Over the past two years Chien and his team have published a series of ‘leap-frogging’ studies, first making a discovery in mice, then replicating it in human embryonic stem cells; then taking the next step in mice, then moving onto to human cells. Next comes the attempt to actually repair cardiac damage in animals and then on to clinical studies in the next 5 years.
“In mice we’re in a position to attempt the repair right now,” Domian said. “We can cause a heart attack, and then look for ways to repair the tissue. The simplest way is to inject the cells into the tissue – we can do that right now in mouse. If that doesn’t work, we have to rely on other technologies.” But, he added, “this is direct proof of concept that a similar approach will work with human ES cells.”
“Now we’re actually in the core of the next level of challenges that face all of regenerative medicine,” said Chien. “In essence I think we’re moving quite quickly now from stem cell biology all the way through towards regenerative medicine.”
*** Contact: B. D. Colen – bd_colen@harvard.edu 617-495-7821 – 617-413-1224
I. Introduction: What are stem cells, and why are they important?
Stem cells have the remarkable potential to develop into many different cell types in the body during early life and growth. In addition, in many tissues they serve as a sort of internal repair system, dividing essentially without limit to replenish other cells as long as the person or animal is still alive. When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell.
Stem cells are distinguished from other cell types by two important characteristics. First, they are unspecialized cells capable of renewing themselves through cell division, sometimes after long periods of inactivity. Second, under certain physiologic or experimental conditions, they can be induced to become tissue- or organ-specific cells with special functions. In some organs, such as the gut and bone marrow, stem cells regularly divide to repair and replace worn out or damaged tissues. In other organs, however, such as the pancreas and the heart, stem cells only divide under special conditions.
Until recently, scientists primarily worked with two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic "somatic" or "adult" stem cells. The functions and characteristics of these cells will be explained in this document. Scientists discovered ways to derive embryonic stem cells from early mouse embryos nearly 30 years ago, in 1981. The detailed study of the biology of mouse stem cells led to the discovery, in 1998, of a method to derive stem cells from human embryos and grow the cells in the laboratory. These cells are called human embryonic stem cells. The embryos used in these studies were created for reproductive purposes through in vitro fertilization procedures. When they were no longer needed for that purpose, they were donated for research with the informed consent of the donor. In 2006, researchers made another breakthrough by identifying conditions that would allow some specialized adult cells to be "reprogrammed" genetically to assume a stem cell-like state. This new type of stem cell, called induced pluripotent stem cells (iPSCs), will be discussed in a later section of this document.
Stem cells are important for living organisms for many reasons. In the 3- to 5-day-old embryo, called a blastocyst, the inner cells give rise to the entire body of the organism, including all of the many specialized cell types and organs such as the heart, lung, skin, sperm, eggs and other tissues. In some adult tissues, such as bone marrow, muscle, and brain, discrete populations of adult stem cells generate replacements for cells that are lost through normal wear and tear, injury, or disease.
Given their unique regenerative abilities, stem cells offer new potentials for treating diseases such as diabetes, and heart disease. However, much work remains to be done in the laboratory and the clinic to understand how to use these cells for cell-based therapies to treat disease, which is also referred to as regenerative or reparative medicine.
Laboratory studies of stem cells enable scientists to learn about the cells’ essential properties and what makes them different from specialized cell types. Scientists are already using stem cells in the laboratory to screen new drugs and to develop model systems to study normal growth and identify the causes of birth defects.
Research on stem cells continues to advance knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. Stem cell research is one of the most fascinating areas of contemporary biology, but, as with many expanding fields of scientific inquiry, research on stem cells raises scientific questions as rapidly as it generates new discoveries.
Other Online Resources
The links included here may connect you to other Internet sites that operate independently of the NIH. The NIH is not responsible for the availability or content of other sites. Permission to reproduce information at other sites may be required. The NIH does not endorse, warrant, or guarantee the information, services, or products described or offered at these external sites.
Cellular Therapy: Potential Treatment for Heart Disease, Food and Drug Administration (FDA), 2004. Despite advances in treatment, ischemic heart disease and congestive heart failure are major causes of death in the United States. Cell therapies for treating these diseases are of interest to medical researchers. This resource outlines the issues surrounding clinical studies of human stem cells and the FDA's role in ensuring safe studies.
Stem Cell Therapy for Heart Patients, National Public Radio Talk of the Nation Audio, April 2004. This one-hour audio program discusses injecting stem cells into heart patients to improve blood flow. This new treatment for heart disease uses the patient's own bone marrow to restore heart function.
Stem Cells and the Future of Regenerative Medicine, by Commission on Life Sciences, 2002. Stem Cells and the Future of Regenerative Medicine summarizes what we know about adult and embryonic stem cells. It also provides an overview of the moral and ethical problems that arise from the use of embryonic stem cells, compares the likely impact of public and private research funding on progress in the field, and discusses approaches to appropriate research oversight. Based on the insights of leading scientists, ethicists, and other authorities, the authors make recommendations regarding the use of existing stem cell lines versus new lines in research, the important role of the federal Related Federal Government Sites in this field of research, and other fundamental issues impacting potential stem cell-based therapies.
Unlocking the Promise of Stem Cells, Harvard Stem Cell Institute, March 2004. View an interactive videoconference in which University researchers discuss the Harvard Stem Cell Institute, created to move cutting-edge research on embryonic stem cells from the lab to the clinic.
Beyond Therapy: Biotechnology and the Pursuit of Happiness, Report from Former President Bush's Council on Bioethics, 2003. Can biotechnology satisfy our human desires—for better children, superior performance, ageless bodies, and happy souls? This report from the President's Council on Bioethics says these possibilities present us with profound ethical challenges and choices. Not declaring "findings," but holding an inquiry—inviting us all to think and debate—the President's Council sought the ideas of dozens of celebrated scientists, thinkers and writers, including such Council members as Francis Fukuyama, Charles Krauthammer, Michael Sandel, and James Q. Wilson, as well as witnesses Steven Pinker, Daniel Schacter, Lawrence Diller, Steven Austad, and S. Jay Olshansky.
PubMed Contains references to literature from more than 4,300 life sciences journals.
Stem Cell Database A joint project of Princeton University and the University of Pennsylvania that contains data on the molecular phenotype of hematopoietic stem cells.
Disease-Specific Organizations and Advocacy Groups
Adult Stem Cell Research Network An internet-based project of The Cell Therapy Foundation designed to be a well-maintained and reliable source of information for the public regarding adult stem cell research, as well as to be a community of practice and collaboration among fellow researchers.
Alliance for Aging Research This citizen advocacy organization works to improve the health and independence of Americans as they age.
ALS Association (ALSA) Dedicated to the fight against Amyotrophic Lateral Sclerosis (also known as Lou Gehrig's Disease), ALSA offers this primer on stem cells.
American Cancer Society Offers information on stem cell transplantation for children with leukemia.
Christopher and Dana Reeve Foundation Funds research on treatments for central nervous system disorders and works to improve the lives of people with disabilities through a grants program, paralysis resource center, and advocacy efforts.
Coalition for the Advancement of Medical Research Advocates the advancement of breakthrough research and technologies in regenerative medicine, including stem cell research and somatic cell nuclear transfer.
National Marrow Donor Program® (NMDP) Maintains an international registry of donors for all sources of blood stem cells used in transplantation: bone marrow, peripheral blood, and umbilical cord blood.
Stem Book is an open access collection of invited, original, peer-reviewed chapters covering a range of topics related to stem cell biology written by top researchers in the field at the Harvard Stem Cell Institute and worldwide. Stem Book is aimed at stem cell and non-specialist researchers.
ExploreStemCells A UK resource for the general public that discusses the use of stem cells in medical treatments and therapies.
The National Academies Publications on stem cells, including Understanding Stem Cells: An Overview of the Science and Issues from the National Academies (2006), Guidelines for Human Embryonic Stem Cell Research (2005), Stem Cells and the Future of Regenerative Medicine (2002), and Scientific and Medical Aspects of Human Reproductive Cloning (2002).
NIH-Supported Science Education Partnership Award (SEPA) Projects
Cellular Universe: The Promise of Stem Cells Educates visitors about advances in cell biology and stem cells so they can make more informed health-related decisions, explore new career options, and better understand the role of scientific research in healthcare.
If a Starfish Can Grow a New Arm, Why Can't I? This Pittsburgh Tissue Engineering Initiative (PTEI) educational program informs middle school students, their teachers, and the general public about tissue engineering and its applications.
Stem Cells: Engage A high school teaching resource on stem cell research developed in Canada.
Stem Cells in the Spotlight and Cloning In Focus The Genetic Science Learning Center at the University of Utah presents these outreach education programs for high school and undergraduate students and teachers.
Tissues of Life: Stem Cells An interactive comic explaining where stem cells are found in the body and how they are gathered.
World Stem Cell Map A resource designed to reflect national policy and whether or not public funds may be used to pursue stem cell research using IVF embryos donated from fertility clinics.
EuroStemCell Eleven academic institutes and enterprises from eight European countries compare stem cell information and evaluate their therapeutic potential.
UK National Stem Cell Network Promotes research activities and events at the national level to speed the translation of basic stem cell research into therapeutic applications in the control of degenerative diseases.
NOVA scienceNOW: Stem Cells Update From the PBS series (originally aired April 19, 2005). Includes dispatches on the politics of stem cells, the cloning process, and related science news.
PBS: Miracle Cell This episode of the series Innovation explores the use of stem cells for regenerative therapies. (Originally aired April 13, 2004)
The Washington Post: Stem Cell Research A collection of articles on stem cell research. (Free registration required to search for other articles within the previous two weeks; fee required to search for older archived articles.)
The Niche A blog hosted by Nature Reports Stem Cells to provide an informal forum for debate and commentary on stem cell research and its wider implications for ethics, policy, business, and medicine.
The Stem Cell Blog Discussion on the science, ethics, business and politics of stem cell research.
American Medical Association (AMA) Provides information on the basics of stem cell research and highlights relevant policy developments.
American Society for Cell Biology (ASCB) Facilitates the exchange of scientific knowledge about cell biology by disseminating research and training students and young investigators.
International Society for Stem Cell Research (ISSCR) Works to exchange information on stem cells, encourage research involving stem cells, and educate the public in all areas of stem cell research and application.
NIH Bioethics Resources on the Web Contains a broad collage of annotated web links that provide background information and various positions on issues in bioethics.
The President's Council on Bioethics Advises the President on ethical issues related to advances in biomedical science and technology, including stem cells.
Research Programs at Universities and Institutions
Harvard Stem Cell Institute Supports research into all aspects of stem cell biology, with special emphasis on those areas with the greatest potential for improving human health.
McGowan Institute for Regenerative Medicine Established for University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center scientists and clinical faculty working to develop tissue engineering, cellular therapies, biosurgery, and artificial and biohybrid organ devices.
National Human Neural Stem Cell Resource Provides neural stem cells harvested from the post-natal, post-mortem, human brain to the research community for stem cell research.
The New York Stem Cell Foundation (NYSCF) Offers grants, fellowships, and symposia for stem cell researchers; educates the public about stem cells; and establishes collaborative stem cell research facilities.
Sloan-Kettering Institute Part of the Memorial Sloan-Kettering Cancer Center, the world's oldest and largest private institution devoted to patient care, education, and research into cancer.
Texas Heart Institute Stem Cell Center Dedicated to the study of adult stem cells and their role in treating cardiovascular disease, including clinical trials (in human patients), as well as many preclinical studies (in the laboratory) using stem cells.
Tulane University Center for Gene Therapy Prepares and distributes well-characterized marrow stromal cells (MSCs) derived from adult human and rodent bone marrow using standardized protocols.
California Institute for Regenerative Medicine (CIRM) Makes grants and provides loans for stem cell research, research facilities, and other research opportunities at California universities and research institutions.
New York Stem Cell Science (NYSTEM) Supports basic, applied, translational or other research and development activities that will advance scientific discoveries in fields related to stem cell biology.
Ohio Center for Stem Cell and Regenerative Medicine A multi-institutional center (Case Western Reserve University, University Hospitals Case Medical Center, the Cleveland Clinic, Athersys, Inc., and Ohio State University). Provides basic and clinical research programs, biomedical and tissue engineering programs, and the development and administration of new therapies.
Stem Cell Research State Laws The National Conference of State Legislatures provides an overview of the state laws and pending legislation on stem cell research.
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