Stem Cell Research Article, Embryonic Cells Information …

In the beginning, one cell becomes two, and two become four. Being fruitful, they multiply into a ball of many cells, a shimmering sphere of human potential. Scientists have long dreamed of plucking those naive cells from a young human embryo and coaxing them to perform, in sterile isolation, the everyday miracle they perform in wombs: transforming into all the 200 or so kinds of cells that constitute a human body. Liver cells. Brain cells. Skin, bone, and nerve.

The dream is to launch a medical revolution in which ailing organs and tissues might be repairednot with crude mechanical devices like insulin pumps and titanium joints but with living, homegrown replacements. It would be the dawn of a new era of regenerative medicine, one of the holy grails of modern biology.

Revolutions, alas, are almost always messy. So when James Thomson, a soft-spoken scientist at the University of Wisconsin in Madison, reported in November 1998 that he had succeeded in removing cells from spare embryos at fertility clinics and establishing the world's first human embryonic stem cell line, he and other scientists got a lot more than they bargained for. It was the kind of discovery that under most circumstances would have blossomed into a major federal research enterprise. Instead the discovery was quickly engulfed in the turbulent waters of religion and politics. In church pews, congressional hearing rooms, and finally the Oval Office, people wanted to know: Where were the needed embryos going to come from, and how many would have to be destroyed to treat the millions of patients who might be helped? Before long, countries around the world were embroiled in the debate.

Most alarmed have been people who see embryos as fully vested, vulnerable members of society, and who decry the harvesting of cells from embryos as akin to cannibalism. They warn of a brave new world of "embryo farms" and "cloning mills" for the cultivation of human spare parts. And they argue that scientists can achieve the same results using adult stem cells immature cells found in bone marrow and other organs in adult human beings, as well as in umbilical cords normally discarded at birth.

Advocates counter that adult stem cells, useful as they may be for some diseases, have thus far proved incapable of producing the full range of cell types that embryonic stem cells can. They point out that fertility clinic freezers worldwide are bulging with thousands of unwanted embryos slated for disposal. Those embryos are each smaller than the period at the end of this sentence. They have no identifying features or hints of a nervous system. If parents agree to donate them, supporters say, it would be unethical not to do so in the quest to cure people of disease.

Few question the medical promise of embryonic stem cells. Consider the biggest United States killer of all: heart disease. Embryonic stem cells can be trained to grow into heart muscle cells that, even in a laboratory dish, clump together and pulse in spooky unison. And when those heart cells have been injected into mice and pigs with heart disease, they've filled in for injured or dead cells and sped recovery. Similar studies have suggested stem cells' potential for conditions such as diabetes and spinal cord injury.

Critics point to worrisome animal research showing that embryonic stem cells sometimes grow into tumors or morph into unwanted kinds of tissuespossibly forming, for example, dangerous bits of bone in those hearts they are supposedly repairing. But supporters respond that such problems are rare and a lot has recently been learned about how to prevent them.

The arguments go back and forth, but policymakers and governments aren't waiting for answers. Some countries, such as Germany, worried about a slippery slope toward unethical human experimentation, have already prohibited some types of stem cell research. Others, like the U.S., have imposed severe limits on government funding but have left the private sector to do what it wants. Still others, such as the U.K., China, Korea, and Singapore, have set out to become the epicenters of stem cell research, providing money as well as ethical oversight to encourage the field within carefully drawn bounds.

In such varied political climates, scientists around the globe are racing to see which techniques will produce treatments soonest. Their approaches vary, but on one point, all seem to agree: How humanity handles its control over the mysteries of embryo development will say a lot about who we are and what we're becoming.

For more than halfof his seven years, Cedric Seldon has been fighting leukemia. Now having run out of options, he is about to become a biomedical pioneerone of about 600 Americans last year to be treated with an umbilical cord blood transplant.

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Stem Cell Research Article, Embryonic Cells Information ...

Stem Cell Therapy in Mexico

Stem Cell MX is dedicated to providing COPD and heart disease patients with information about stem cell therapy at Angeles Health International, Mexicos largest private hospital network.

Stem Cell Therapy is a fast growing area of medical research. Research into how stem cells can cure a number of conditions has been extensive over the past 3 decades and here at Stem Cell MX we are proud to be at the forefront of breakthrough discoveries and treatments. We dedicate ourselves to providing you with information about Stem Cells and what they can do for you.

At Stem Cell MX we can use Stem Cell therapy to treat 11 core treatable conditions including chronic obstructive pulmonary disease (COPD), heart conditions and joint conditions, such as osteoarthritis. We use two types of stem cell programs; autologous, meaning that we use your own stem cells, and allogeneic, where we use donated adult stem cells from one of the best labs in the world.

Stem cell research has had bad press over the years due to the misconception that Stem Cells can only come from embryos. This isnt true. Here at Stem Cell MX we only use Adult Stem Cells which have been harvested from either the donor or the patients themselves.

If you want to find out more about stem cell therapy with no obligation then contact us today. Our stem cell clinical trials are based on thirty years of research and clinical experience conducted by leading researchers and clinicians in Europe and the United States.

To find out the basics about stem cells read An Introduction to Stem Cells

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Stem Cell Therapy in Mexico

What are induced pluripotent stem cells? [Stem Cell …

Introduction: What are stem cells, and why are they important? What are the unique properties of all stem cells? What are embryonic stem cells? What are adult stem cells? What are the similarities and differences between embryonic and adult stem cells? What are induced pluripotent stem cells? What are the potential uses of human stem cells and the obstacles that must be overcome before these potential uses will be realized? Where can I get more information?

Induced pluripotent stem cells (iPSCs) are adult cells that have been genetically reprogrammed to an embryonic stem celllike state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells. Although these cells meet the defining criteria for pluripotent stem cells, it is not known if iPSCs and embryonic stem cells differ in clinically significant ways. Mouse iPSCs were first reported in 2006, and human iPSCs were first reported in late 2007. Mouse iPSCs demonstrate important characteristics of pluripotent stem cells, including expressing stem cell markers, forming tumors containing cells from all three germ layers, and being able to contribute to many different tissues when injected into mouse embryos at a very early stage in development. Human iPSCs also express stem cell markers and are capable of generating cells characteristic of all three germ layers.

Although additional research is needed, iPSCs are already useful tools for drug development and modeling of diseases, and scientists hope to use them in transplantation medicine. Viruses are currently used to introduce the reprogramming factors into adult cells, and this process must be carefully controlled and tested before the technique can lead to useful treatment for humans. In animal studies, the virus used to introduce the stem cell factors sometimes causes cancers. Researchers are currently investigating non-viral delivery strategies. In any case, this breakthrough discovery has created a powerful new way to "de-differentiate" cells whose developmental fates had been previously assumed to be determined. In addition, tissues derived from iPSCs will be a nearly identical match to the cell donor and thus probably avoid rejection by the immune system. The iPSC strategy creates pluripotent stem cells that, together with studies of other types of pluripotent stem cells, will help researchers learn how to reprogram cells to repair damaged tissues in the human body.

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What are induced pluripotent stem cells? [Stem Cell ...

10. The Promise of Induced Pluripotent Stem Cells (iPSCs …

Charles A. Goldthwaite, Jr., Ph.D.

In 2006, researchers at Kyoto University in Japan identified conditions that would allow specialized adult cells to be genetically "reprogrammed" to assume a stem cell-like state. These adult cells, called induced pluripotent stem cells (iPSCs), were reprogrammed to an embryonic stem cell-like state by introducing genes important for maintaining the essential properties of embryonic stem cells (ESCs). Since this initial discovery, researchers have rapidly improved the techniques to generate iPSCs, creating a powerful new way to "de-differentiate" cells whose developmental fates had been previously assumed to be determined.

Although much additional research is needed, investigators are beginning to focus on the potential utility of iPSCs as a tool for drug development, modeling of disease, and transplantation medicine. The idea that a patient's tissues could provide him/ her a copious, immune-matched supply of pluripotent cells has captured the imagination of researchers and clinicians worldwide. Furthermore, ethical issues associated with the production of ESCs do not apply to iPSCs, which offer a non-controversial strategy to generate patient-specific stem cell lines. As an introduction to this exciting new field of stem cell research, this chapter will review the characteristics of iPSCs, the technical challenges that must be overcome before this strategy can be deployed, and the cells' potential applications to regenerative medicine.

As noted in other chapters, stem cells represent a precious commodity. Although present in embryonic and adult tissues, practical considerations such as obtaining embryonic tissues and isolating relatively rare cell types have limited the large-scale production of populations of pure stem cells (see the Chapter, "Alternate Methods for Preparing Pluripotent Stem Cells" for details). As such, the logistical challenges of isolating, culturing, purifying, and differentiating stem cell lines that are extracted from tissues have led researchers to explore options for "creating" pluripotent cells using existing non-pluripotent cells. Coaxing abundant, readily available differentiated cells to pluripotency would in principle eliminate the search for rare cells while providing the opportunity to culture clinically useful quantities of stem-like cells.

One strategy to accomplish this goal is nuclear reprogramming, a technique that involves experimentally inducing a stable change in the nucleus of a mature cell that can then be maintained and replicated as the cell divides through mitosis. These changes are most frequently associated with the reacquisition of a pluripotent state, thereby endowing the cell with developmental potential. The strategy has historically been carried out using techniques such as somatic cell nuclear transfer (SCNT),1,2 altered nuclear transfer (ANT),3,4 and methods to fuse somatic cells with ESCs5,6 (see "Alternate Methods for Preparing Pluripotent Stem Cells" for details of these approaches). From a clinical perspective, these methods feature several drawbacks, such as the creation of an embryo or the development of hybrid cells that are not viable to treat disease. However, in 2006, these efforts informed the development of nuclear reprogramming in vitro, the breakthrough method that creates iPSCs.

This approach involves taking mature "somatic" cells from an adult and introducing the genes that encode critical transcription factor proteins, which themselves regulate the function of other genes important for early steps in embryonic development (See Fig. 10.1). In the initial 2006 study, it was reported that only four transcription factors (Oct4, Sox2, Klf4, and c-Myc) were required to reprogram mouse fibroblasts (cells found in the skin and other connective tissue) to an embryonic stem celllike state by forcing them to express genes important for maintaining the defining properties of ESCs.7 These factors were chosen because they were known to be involved in the maintenance of pluripotency, which is the capability to generate all other cell types of the body. The newly-created iPSCs were found to be highly similar to ESCs and could be established after several weeks in culture.7,8 In 2007, two different research groups reached a new milestone by deriving iPSCs from human cells, using either the original four genes9 or a different combination containing Oct4, Sox2, Nanog, and Lin28.10 Since then, researchers have reported generating iPSCs from somatic tissues of the monkey11 and rat.12,13

However, these original methods of reprogramming are inefficient, yielding iPSCs in less than 1% of the starting adult cells.14,15 The type of adult cell used also affects efficiency; fibroblasts require more time for factor expression and have lower efficiency of reprogramming than do human keratinocytes, mouse liver and stomach cells, or mouse neural stem cells.1419

Several approaches have been investigated to improve reprogramming efficiency and decrease potentially detrimental side effects of the reprogramming process. Since the retroviruses used to deliver the four transcription factors in the earliest studies can potentially cause mutagenesis (see below), researchers have investigated whether all four factors are absolutely necessary. In particular, the gene c-Myc is known to promote tumor growth in some cases, which would negatively affect iPSC usefulness in transplantation therapies. To this end, researchers tested a three-factor approach that uses the orphan nuclear receptor Esrrb with Oct4 and Sox2, and were able to convert mouse embryonic fibroblasts to iPSCs.20 This achievement corroborates other reports that c-Myc is dispensable for direct reprogramming of mouse fibroblasts.21 Subsequent studies have further reduced the number of genes required for reprogramming,2226 and researchers continue to identify chemicals that can either substitute for or enhance the efficiency of transcription factors in this process.27 These breakthroughs continue to inform and to simplify the reprogramming process, thereby advancing the field toward the generation of patient-specific stem cells for clinical application. However, as the next section will discuss, the method by which transcription factors are delivered to the somatic cells is critical to their potential use in the clinic.

Figure 10.1. Generating Induced Pluripotent Stem Cells (iPSCs).

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