The Case for Adult Stem Cell Research

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BIOLOGY & MEDICINE

The Case for Adult Stem Cell Research

by Wolfgang Lillge, M.D.

(Full text of article from Winter 2001-2002 21st Century)

Problems of Therapeutic Cloning

Whoever Would Cure, Must Use Adult Stem Cells

Human Treatments

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The question of stem cells is currently the dominant subject in the debate over biotechnology and human genetics: Should we use embryonic stem cells or adult stem cells for future medical therapies? Embryonic stem cells are taken from a developing embryo at the blastocyst stage, destroying the embryo, a developing human life. Adult stem cells, on the other hand, are found in all tissues of the growing human being and, according to latest reports, also have the potential to transform themselves into practically all other cell types, or revert to being stem cells with greater reproductive capacity. Embryonic stem cells have not yet been used for even one therapy, while adult stem cells have already been successfully used in numerous patients, including for cardiac infarction (death of some of the heart tissue).

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The Case for Adult Stem Cell Research

Pros & Cons of Embryonic Stem Cell Research

Spencer Platt/Getty Images News/Getty Images

Pros

Embryonic stem cells are thought by most scientists and researchers to hold potential cures for spinal cord injuries, multiple sclerosis, diabetes, Parkinson's disease, cancer, Alzheimer's disease, heart disease, hundreds of rare immune system and genetic disorders and much more.

Scientists see almost infinite value in the use of embryonic stem cell research to understand human development and the growth and treatment of dieases.

Actual cures are many years away, though, since research has not progressed to the point where even one cure has yet been generated by embryonic stem cell research.

Over 100 million Americans suffer from diseases that eventually may be treated more effectively or even cured with embryonic stem cell therapy. Some researchers regard this as the greatest potential for the alleviation of human suffering since the advent of antibiotics.

Many pro-lifers believe that the proper moral and religious course of action is to save existing life through embryonic stem cell therapy.

Cons

Some staunch pro-lifers and most pro-life organizations regard the destruction of the blastocyst, which is a laboratory-fertilized human egg, to be the murder of human life. They believe that life begins at conception, and that destruction of this pre-born life is morally unacceptable.

They believe that it is immoral to destroy a few-days-old human embryo, even to save or reduce suffering in existing human life.

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Pros & Cons of Embryonic Stem Cell Research

somatic stem cell – Learn Genetics

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Stem Cells

Stem Cell Quick Reference

Are you confused about all the different types of stem cells? Read on to learn where different types of stem cells come from, what their potential is for use in therapy, and why some types of stem cells are shrouded in controversy.

Researchers are working on new ways to use stem cells to cure diseases and heal injuries. Learn more about unlocking stem cell potential.

Somatic stem cells (also called adult stem cells) exist naturally in the body. They are important for growth, healing, and replacing cells that are lost through daily wear and tear.

Potential as therapy Stem cells from the blood and bone marrow are routinely used as a treatment for blood-related diseases. However, under natural circumstances somatic stem cells can become only a subset of related cell types. Bone marrow stem cells, for example, differentiate primarily into blood cells. This partial differentiation can be an advantage when you want to produce blood cells; but it is a disadvantage if you're interested in producing an unrelated cell type.

Special considerations Most types of somatic stem cells are present in low abundance and are difficult to isolate and grow in culture. Isolation of some types could cause considerable tissue or organ damage, as in the heart or brain. Somatic stem cells can be transplanted from donor to patient, but without drugs that suppress the immune system, a patient's immune system will recognize transplanted cells as foreign and attack them.

Ethical considerations Therapy involving somatic stem cells is not controversial; however, it is subject to the same ethical considerations that apply to all medical procedures.

Embryonic stem (ES) cells are formed as a normal part of embryonic development. They can be isolated from an early embryo and grown in a dish.

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Stem Cell Therapy StemCell Doctors | Stem Cell Treatments

Stem Cell Therapy

After many years of research, it now possible to provide affordable same-day stem cell therapy to dogs and cats suffering from a variety of degenerative diseases and injuries. With our Stemlogix in-clinic stem cell isolation process, our board certified veterinarians can extract fat tissue, isolate millions of regenerative stem cells and deliver them back to the patient all in about 90 minutesin just one office visit!

This quick turnaround maintains the highest cell viability and functionality which gives patients the best chance for clinical improvement. Stemlogix stem cell therapy can relieve pain, increase range of motion in joints and improve the quality of life in pets suffering from the following conditions:

Arthritis Joint pain Cartilage damage Tendon & ligament damage Hip dysplasia

Often your pet will have renewed energy and freedom of movement. Talk to your veterinarian about gradually reintroducing activity in order to prevent aggravating the condition.

Stem cells are delivered to an area of damaged tissue where they stimulate regeneration and aid in repair of the damaged tissue. In addition, the stem cells have the ability to differentiate into many different cell types such as tendon, bone, ligament and cartilage, which may further help in the repair of damaged tissue.

Your pet will undergo a simple surgical procedure to obtain a fat tissue sample either from the shoulder area or from the abdomen. The tissue sample will be processed in about an hour directly on-site at our state-of-the-art facility where highly viable & potent regenerative stem cells are obtained. The stem cells are then delivered back to your pet at the injury site and/or with an intravenous (IV) infusion.

The Stemlogix stem cells are derived from the animals own tissue and they can be injected in large concentrations in the area of injury. Because the injected cells are derived from the animals own tissue and are minimally manipulated there is almost no risk of rejection or reaction. The main goals of stem cell therapy are to provide long-term anti-inflammatory effects, slow the progression of cartilage degeneration and initiate healing of the damaged tissue. This provides pain relief within a few days to a few weeks after the injection with further improvement as healing progresses.

For more information, please visit http://www.stemlogix.com

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New measurements reveal differences between stem cells for …

By growing two types of stem cells in a "3-D culture" and measuring their ability to produce retinal cells, a team lead by St. Jude Children's Research Hospital researchers has found one cell type to be better at producing retinal cells.

The research not only reveals which stem cell type might be better for treating retinal degeneration, but it also demonstrates a standardized method for quantifying the effectiveness of different stem cells for such therapies.

The research was led by Michael Dyer, Ph.D., a member of the St. Jude Department of Developmental Neurobiology and a Howard Hughes Medical Institute investigator. The findings were published in the July 2 edition of the journal Cell Stem Cell.

Stem cells are immature cells that can differentiate into more specialized cells in the body. In early clinical trials, researchers are testing whether stem cells can be differentiated into cells to replace those that are defective and die off in diseases such as age-related macular degeneration, retinitis pigmentosa and Stargardt's disease. Such degeneration is the leading cause of vision loss, affecting more than 10 million people in the U.S.more than cataracts and glaucoma combined.

While such clinical trials have shown early promise, there are many scientific questions to be answered. "One important question is whether it makes a difference where the stem cells come from," Dyer said. "Our research sought to explore that question and also to learn more about the biology of these stem cells."

The researchers compared two types of stem cells called "induced pluripotent stem cells," which can be generated from adult cells. The stem cells they compared were fibroblast-derived cells generated from skin, and those generated from mature eye cells called rod photoreceptor cells.

Scientists previously thought that induced pluripotent stem cells could not be made from adult neurons without introducing a mutation that switches off a key regulatory gene called p53. Dyer's lab developed a new method for making stem cells from neurons that did not require p53 inactivation. This 3-D culture technique involved surrounding the neurons undergoing reprogramming with normal retinal neurons, to create a more natural environment for producing stem cells from neurons. This technique contrasts with the more common culture technique of growing the cells in layers on culture dishes, which is not successful for such cells. Once the stem cells are produced, they can then be used to make retinal cells in 3-D cultures.

Besides the 3-D culture technique, the researchers also used a set of measurements, called STEM-RET, which enabled them to quantify precisely how successful different retinal cells are in generating retinal cells. Their STEM-RET analysis revealed that the rod-derived stem cells produced more retinal cells than did the fibroblast stem cells. The fibroblast-derived retinal cells were missing some cell types needed for fully functional retinas.

Dyer and his colleagues also explored the biological differences in the two stem cell types that could explain their differences in producing retinal cells. Specifically, the researchers analyzed differences in the epigenetic control machinery of the two types. Such epigenetic machinery of cells consists of biological switches that control the cell's genes. These are distinct from the genetic control machinery built into the DNA structure of the cell's genes themselves.

Scientists believe that different stem cell types may retain an "epigenetic memory"a distinctive set of epigenetic switches, even as they are reprogrammed from mature cell types. This "memory" affects how well the stem cells produce different cell types.

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Postdoctoral position in Stem Cell Development and Cancers

Postdoctoral positions are immediately available in the laboratory of Dr. Jian Xu, in the Childrens Research Institute of UTSouthwestern Medical Center to study the epigenetic regulation of normal and malignant blood stem cell development. Our laboratory focuses on the intersection of transcriptional control with stem cell biology, hematopoiesis and cancer. We employ epigenetics, functional genomics, genome editing, and mouse genetics to define epigenetic and genetic programs controlling blood stem cell development, and how these processes go awry in cancer progression. By comparing the ontogeny of gene networks in normal and neoplastic hematopoiesis, we aim to understand how non-coding regulatory genome, lineage-specifying regulators, and epigenetic modulators cooperate to control developmental potency, and how aberrations lead to cancer development. The laboratory is equipped with cutting-edge genomics and bioinformatics platforms, and has access to numerous shared facilities including metabolomics, imaging, and flow cytometry. Our laboratory brings together enthusiastic scientists with diverse backgrounds, and provides a wide range of perspectives in a multi-disciplinary and collaborative team setting. Please refer to our representative publications for details about the ongoing research: Nature 460:1093-1097; Science 334:993-996; Cell, 151:929-931; Dev Cell, 23:796-811; Mol Cell, 57:304-316; Cell Stem Cell 14:68-80; NEJM, 365:807-814; G&D 23:2824-2838.

The successful candidate must hold a Ph.D. and/or M.D. degree with a strong background in mouse genetics, blood cell development and disorders, molecular biology, or a related field. The ideal candidate will exhibit independence, flexibility and creativity with a record of scientific productivity. Previous experience in generating and analyzing mouse models, epigenetics, genomic engineering, and/or hematology-oncology is strongly preferred.

To apply please submit CV, a short summary of research interest and experience, and a list of three references to:

Jian Xu, PhD

Assistant Professor, Childrens Research Institute

CPRIT Scholar in Cancer Research

American Society of Hematology Scholar

UT Southwestern Medical Center 5323 Harry Hines Blvd. Dallas, TX 75390-8502

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Postdoctoral position in Stem Cell Development and Cancers

Embryonic stem cells: where do they come from and what can …

Embryonic stem cells are derived from very early embryos called blastocysts; the diameter of a human blastocyst is roughly four times that of a human hair

A human blastocyst next to a human hair

A mouse blastocyst aged 3.5 days; the inner cell mass is coloured green and the trophectoderm is coloured red

Embryonic stem cells genetically modified to glow green under a fluorescent lamp

A chimeric mouse and his offspring; the offspring have a gene for black hair from the ES cells used to make their father

Neurons (nerve cells) made in the lab from human embryonic stem cells

Embryonic stem cells are grown from cells found in the embryo when it is just a few days old. In humans, mice and other mammals, the embryo is a ball of approximately 100 cells at this stage. It is known as a blastocyst and has two parts:

Some of the cellsin the inner cell mass are pluripotent: they can make every type of cell in the body.

If an inner cell mass is taken from a mouse blastocyst and given the right nutrients, the pluripotent cells cangrow in the laboratory. The process of cell maturation and specialization that would normally take place in the embryo stops. Instead, the cells multiply to make more undifferentiated cells that resemble the cells of the inner cell mass. These laboratory-grown cells are called embryonic stem (ES) cells.

Embryonic stem cells can make copies of themselves and make other types of more specialized cells

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Embryonic Stem Cells – HowStuffWorks

Once an egg cell is fertilized by a sperm, it will divide and become an embryo. In the embryo, there are stem cells that are capable of becoming all of the various cell types of the human body. For research, scientists get embryos in two ways. Many couples conceive by the process of in vitro fertilization. In this process, a couple's sperm and eggs are fertilized in a culture dish. The eggs develop into embryos, which are then implanted in the female. However, more embryos are made than can be implanted. So, these embryos are usually frozen. Many couples donate their unused embryos for stem cell research.

The second way in which scientists get embryos is therapeutic cloning. This technique merges a cell (from the patient who needs the stem cell therapy) with a donor egg. The nucleus is removed from the egg and replaced with the nucleus of the patient's cell. (For a detailed look at the process, see How Cloning Works) This egg is stimulated to divide either chemically or with electricity, and the resulting embryo carries the patient's genetic material, which significantly reduces the risk that his or her body will reject the stem cells once they are implanted.

Both methods -- using existing fertilized embryos and creating new embryos specifically for research purposes -- are controversial. But before we get into the controversy, let's find out how scientists get stem cells to replicate in a laboratory setting in order to study them.

When an embryo contains about eight cells, the stem cells are totipotent - they can develop into all cell types. At three to five days, the embryo develops into a ball of cells called a blastocyst. A blastocyst contains about 100 cells total and the stem cells are inside. At this stage, the stem cells are pluripotent - they can develop into almost any cell type.

To grow the stem cells, scientists remove them from the blastocyst and culture them (grow them in a nutrient-rich solution) in a Petri dish in the laboratory. The stem cells divide several times and scientists divide the population into other dishes. After several months, there are millions of stem cells. If the cells continue to grow without differentiating, then the scientists have a stem cell line. Cell lines can be frozen and shared between laboratories. As we will see later, stem cell lines are necessary for developing therapies.

Today, many expectant mothers are asked about umbilical cord banking -- the process of storing umbilical cord blood after giving birth. Why would someone want to do that? Once a mother gives birth, the umbilical cord and remaining blood are often discarded. However, this blood also contains stem cells from the fetus. Umbilical cord blood can be harvested and the embryonic stem cells grown in culture. Unlike embryonic stem cells from earlier in development, fetal stem cells from umbilical cord blood are multipotent - they can develop into a limited number of cell types.

Now that you have a better understanding of embryonic stem cells, let's look at adult stem cells.

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Embryonic Stem Cells - HowStuffWorks

Embryonic Stem Cell Research Pros and Cons | HRF

There may not be a greater debate in the medical community right now than that of embryonic stem cell research. Initially banned by the Federal government, these stem cells often originate from human embryos that were created for couples with reproductive issues and would be discarded. These stem cells are thought to be the key that will unlock the cure to many diseases, from Alzheimers to rare immune and even genetic disorders. On the other side of the issue, some see the destruction of an embryo as the murder of an unborn child.

The primary benefit of this research is the enormous amount of potential that it holds. Embryonic stem cells have the ability to create new organs, tissues, and systems within the human body. With a little guidance from scientists, these stem cells have shown that they can become new organs, new blood vessels, and even new ligaments for those with ACL tears. By culturing stem cells and them implanting them, recovery times could be halved for many serious injuries, illnesses, and diseases.

Because nearly one-third of the population could benefit from treatments and therapies that could originate from embryonic stem cell research, many scientists believe that this field could alleviate as much human suffering as the development of antibiotics was able to do. Because funding was restricted on embryonic stem cell lines for several years, however, the chances of any therapies being viable in the near future are slim.

The primary argument against this research is a moral one. Some people see the creation of an embryo as the creation of life, so to terminate that life would equate to murder. This primarily originates from a point of view where life as we define it begins at conception, which would mean that any medical advancement from this research would be at best unethical.

Those against this research argue that since the creation of this research field in the early 1980s, there have been no advancements in it whatsoever. Because of this lack of advancement, it could mean decades of additional research, thousands of embryos destroyed to further that research, and that is morally unacceptable for some.

The debate about embryonic stem cell research isnt in the potential benefits that this field of study could produce. It is in the ethics and morality of how embryonic stem cells are created. There often is no in-between view in this area: you either define life at some part of the physical development of the human body during the pregnancy or you define it at conception. This view then tends to lead each person to one side of this debate. Where do you stand?

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Stem cell gene therapy holds promise for eliminating HIV …

by Mirabai Vogt-James The scientists, led by Jerome Zack (left) and Scott Kitchen, found that the technique decreased HIV levels in mice by 80 to 95 percent. Credit: UCLA Broad Stem Cell Research Center

cientists at the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research are one step closer to engineering a tool that could one day arm the body's immune system to fight HIVand win. The new technique harnesses the regenerative capacity of stem cells to generate an immune response to the virus.

The findings were published today in the journal Molecular Therapy.

"We hope this approach could one day allow HIV-positive individuals to reduce or even stop their current HIV drug regimen and clear the virus from the body altogether," said Scott Kitchen, the study's lead author and a member of the Broad Stem Cell Research Center. "We also think this approach could possibly be extended to other diseases." Kitchen also is a member of the UCLA AIDS Institute and an associate professor of medicine in the division of hematology and oncology at the David Geffen School of Medicine at UCLA.

Kitchen and his colleagues were the first to report the use of an engineered molecule called a chimeric antigen receptor, or CAR, in blood-forming stem cells. Blood-forming stem cells are capable of turning into any type of blood cell, including T cells, the white blood cells that are central to the immune system. In a healthy immune system, T cells can usually rid the body of viral or bacterial infection. But HIV is too strong and mutates too rapidly for T cells to fight against the virus.

The researchers inserted a gene for a CAR into blood-forming stem cells in the lab. The CAR, which is a two-part receptor that recognizes an antigen, was engineered to be carried by T cells and direct them to locate and kill HIV-infected cells. The CAR-modified blood stem cells were then transplanted into HIV-infected mice that had been genetically engineered with human immune systems. (As a result, HIV infection causes disease similar to that in humans.)

The researchers found that the CAR-carrying blood stem cells successfully turned into functional T cells that could kill HIV-infected cells in the mice. The result was a decrease in HIV levels of 80 to 95 percent.

The findings strongly suggest that stem cell-based gene therapy with a CAR may be a feasible and effective treatment for chronic HIV infection in humans.

The world's leading infectious killer, HIV has caused approximately 40 million deaths worldwide since it was first identified in the early 1980s. Once HIV invades the body, it targets the very immune cells that are working against it, using the machinery of T cells to make copies of itself to spread through the body. This kills the T cells and weakens the immune system so much that the body can't fight even a simple infection. Certain drugs help suppress the virus, but since the human immune system can't clear the virus from the body, people with HIV have the virus for life.

"Despite increased scientific understanding of HIV and better prevention and treatment with available drugs, a majority of the 35 million people living with HIV, and millions more at risk of infection, do not have adequate access to prevention and treatment, and there is still no practical cure," said Jerome Zack, professor of medicine and of microbiology, immunology and molecular genetics in the UCLA David Geffen School of Medicine and a co-author of the study. "With the CAR approach, we aim to change that." Zack is co-director of the UCLA AIDS Institute and is affiliated with UCLA's Jonsson Comprehensive Cancer Center and a member of the Broad Stem Cell Research Center.

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