Basic questions about stem cells

Published on March 20, 2012 at 12:11 am

Basic questions about stem cells

Basic questions about stem cells

Basic questions about stem cells

  1. What are stem cells?
    Stem cells are cells that have the potential to develop into some or many different cell types in the body, depending on whether they are multipotent or pluripotent. Serving as a sort of repair system, they can theoretically divide without limit to replenish other cells for as long as the person or animal is still alive. When a stem cell divides, each “daughter” cell has the potential to either 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.For a discussion of the different kinds of stem cells, such as embryonic stem cells, adult stem cells, or induced pluripotent stem cells.
  2. What classes of stem cells are there?
    Stem cells may be pluripotent or multipotent.

    • Pluripotent stem cells can give rise to any type of cell in the body except those needed to support and develop a fetus in the womb.
    • Stem cells that can give rise only to a small number of different cell types are called multipotent.
  3. Where do stem cells come from?
    There are several sources of stem cells. Pluripotent stem cells can be isolated from human embryos that are a few days old. Cells from these embryos can be used to create pluripotent stem cell “lines” —cell cultures that can be grown indefinitely in the laboratory. Pluripotent stem cell lines have also been developed from fetal tissue (older than 8 weeks of development).In late 2007, scientists identified conditions that would allow some specialized adult human cells to be reprogrammed genetically to assume a stem cell-like state. These stem cells are called induced pluripotent stem cells (iPSCs). IPSCs are adult cells that have been genetically reprogrammed to an embryonic stem cell–like 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 treatments 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.

    Non-embryonic, or “adult” stem cells have been identified in many organs and tissues. Typically there is a very small number of multipotent stem cells in each tissue, and these cells have a limited capacity for proliferation, thus making it difficult to generate large quantities of these cells in the laboratory. Stem cells are thought to reside in a specific area of each tissue (called a “stem cell niche”) where they may remain quiescent (non-dividing) for many years until they are activated by a normal need for more cells, or by disease or tissue injury. These cells are also called somatic stem cells.

  4. Why do scientists want to use stem cell lines?
    Once a stem cell line is established from a cell in the body, it is essentially immortal, no matter how it was derived. That is, the researcher using the line will not have to go through the rigorous procedure necessary to isolate stem cells again. Once established, a cell line can be grown in the laboratory indefinitely and cells may be frozen for storage or distribution to other researchers.Stem cell lines grown in the lab provide scientists with the opportunity to “engineer” them for use in transplantation or treatment of diseases. For example, before scientists can use any type of tissue, organ, or cell for transplantation, they must overcome attempts by a patient’s immune system to reject the transplant. In the future, scientists may be able to modify human stem cell lines in the laboratory by using gene therapy or other techniques to overcome this immune rejection. Scientists might also be able to replace damaged genes or add new genes to stem cells in order to give them characteristics that can ultimately treat diseases.

Healthcare Questions

  1. Why are doctors and scientists so excited about human embryonic stem cells?
    Stem cells have potential in many different areas of health and medical research. To start with, studying stem cells will help us to understand how they transform into the dazzling array of specialized cells that make us what we are. Some of the most serious medical conditions, such as cancer and birth defects, are due to problems that occur somewhere in this process. A better understanding of normal cell development will allow us to understand and perhaps correct the errors that cause these medical conditions.Another potential application of stem cells is making cells and tissues for medical therapies. Today, donated organs and tissues are often used to replace those that are diseased or destroyed. Unfortunately, the number of people needing a transplant far exceeds the number of organs available for transplantation. Pluripotent stem cells offer the possibility of a renewable source of replacement cells and tissues to treat a myriad of diseases, conditions, and disabilities including Parkinson’s disease, amyotrophic lateral sclerosis, spinal cord injury, burns, heart disease, diabetes, and arthritis.
  2. Have human embryonic stem cells been used successfully to treat any human diseases yet?
    Scientists have only been able to do experiments with human embryonic stem cells (hESCs) since 1998, when a group led by Dr. James Thomson at the University of Wisconsin developed a technique to isolate and grow the cells.The NIH funded its first basic research study on hESCs in 2002. Since that time, biotechnology companies have built upon those basic foundations to begin developing stem cell–based human therapies. There are currently two active clinical trials using cells derived from human embryonic stem cells, both being conducted by a biotechnology company called ACT. The company has laboratories in Marlborough, Massachusetts, and corporate offices in Santa Monica, California. ACT has begun enrolling patients for Phase I (safety and tolerability) clinical trials of two hESC-derived stem cell products:

    1. The first ACT trial is testing the safety of hESC-derived retinal cells to treat patients with an eye disease called Stargardt’s Macular Dystrophy (SMD).
    2. The second ACT trial is testing the safety of hESC-derived retinal cells to treat patients with age-related macular degeneration.

    In January, 2012, the investigators published a preliminary report on the first two patients treated with hESC-derived cells: http://www.ncbi.nlm.nih.gov/
    pubmed/22281388.

    A third clinical trial using hESC-derived cells was halted on November 14, 2011. The trial was being conducted by a biotechnology called Geron, located in Menlo Park, California. Four patients with recent spinal cord injuries had been enrolled for its clinical trial of a hESC-derived therapy. The trial was testing the safety of using hESC-derived cells to achieve restoration of spinal cord function. Oligodendrocyte progenitor cells derived from hESCs were being injected directly into the lesion site of the patient’s injured spinal cord. On November 14, Geron announced that it was discontinuing its stem cell programs to concentrate on cancer programs.

    Bone marrow contains blood-forming stem cells (hematopoietic stem cells) that have been used for decades to treat blood cancers and other blood disorders. Umbilical cord blood is another source of hematopoietic stem cells that is being used in treatment. You can see a list of diseases that may currently be treated with hematopoietic stem cells at the website of the National Marrow Donor Program.

  3. What will be the best type of stem cell to use for therapy?
    Pluripotent stem cells, while having great therapeutic potential, face formidable technical challenges. First, scientists must learn how to control their development into all the different types of cells in the body. Second, the cells now available for research are likely to be rejected by a patient’s immune system. Another serious consideration is that the idea of using stem cells from human embryos or human fetal tissue troubles many people on ethical grounds.Until recently, there was little evidence that multipotent adult stem cells could change course and provide the flexibility that researchers need in order to address all the medical diseases and disorders they would like to. New findings in animals, however, suggest that even after a stem cell has begun to specialize, it may be more flexible than previously thought.

    There are currently several limitations to using traditional adult stem cells. Although many different kinds of multipotent stem cells have been identified, adult stem cells that could give rise to all cell and tissue types have not yet been found. Adult stem cells are often present in only minute quantities and can therefore be difficult to isolate and purify. There is also evidence that they may not have the same capacity to multiply as embryonic stem cells do. Finally, adult stem cells may contain more DNA abnormalities—caused by sunlight, toxins, and errors in making more DNA copies during the course of a lifetime. These potential weaknesses might limit the usefulness of adult stem cells.

    It is now possible to reprogram adult somatic cells to become like embryonic stem cells (induced pluripotent stem cells, iPSCs) through the introduction of embryonic genes. Thus, a source of cells can be generated that are specific to the donor, thereby increasing the chance of compatibility if such cells were to be used for tissue regeneration. However, like embryonic stem cells, determination of the methods by which iPSCs can be completely and reproducibly committed to appropriate cell lineages is still under investigation. Since they are derived from adult cells, iPSCs may also suffer DNA abnormalities, as described in the previous paragraph.

  4. I have Parkinson’s Disease. Is there a clinical trial that I can participate in that uses stem cells as therapy?
    The public may search a database of NIH-sponsored clinical trials atwww.clinicaltrials.gov. Enter the search terms of interest (in this case, Parkinson’s Disease and stem cells) to search for applicable clinical trials.
  5. Where can I donate umbilical cord stem cells?
    NIH cannot accept donated umbilical cord stem cells from the general public. The National Marrow Donor Program maintains a Web page on donating cord blood athttp://www.marrow.org/HELP/Donate_Cord_Blood_Share_Life/index.html.

Research and Policy Questions

  1. Which research is best to pursue?
    The development of stem cell lines that can produce many tissues of the human body is an important scientific breakthrough. This research has the potential to revolutionize the practice of medicine and improve the quality and length of life. Given the enormous promise of stem cell therapies for so many devastating diseases, NIH believes that it is important to simultaneously pursue all lines of research and search for the very best sources of these cells.
  2. Why not use adult stem cells instead of using human embryonic stem cells in research?
    Human embryonic stem cells are thought to have much greater developmental potential than adult stem cells. This means that embryonic stem cells may be pluripotent—that is, able to give rise to cells found in all tissues of the embryo except for germ cells rather than being merely multipotent—restricted to specific subpopulations of cell types, as adult stem cells are thought to be. However, a newer type of reprogrammed adult cells, called induced pluripotent stem cells, has proven to be pluripotent.
  3. What are the NIH Guidelines on the utilization of stem cells derived from human fetal tissue (embryonic germ cells)?
    The Federal Register Announcement National Institutes of Health Guidelines for Research Using Human Pluripotent Stem Cells (230k PDF; get Adobe Reader), published August 25, 2000, was “superceded as it pertains to embryonic stem cell research” on November 14, 2001). However, Section II. B, titled “Utilization of Human Pluripotent Stem Cells Derived from Human Fetal Tissue,” still governs human embryonic germ cell research. In addition, Section III, titled “Areas of Research Involving Human Pluripotent Stem Cells That Are Ineligible for NIH Funding,” governs both human embryonic stem cell and human embryonic germ cell research.
  4. May individual states pass laws to permit human embryonic stem cell research?
    Individual states have the authority to pass laws to permit human embryonic stem cell research using state funds. Unless Congress passes a law that bans it, states may pay for research using human embryonic stem cell lines that are not eligible for federal funding.
  5. Where can I find information about patents obtained for stem cells?
    The U.S. Patent and Trademark Office offers a full-text search of issued patents and published applications. Try searching for “stem cell” or “stem cells.”

Cell Line Availability and the Registry

  1. I am a scientist funded by the NIH. How many cell lines are available to me, and how do I get them?
    The NIH has developed the NIH Human Embryonic Stem Cell Registry. This Registry lists all cell lines that are eligible for use in NIH funded research.The number of lines available for use in NIH funded research continues to expand, as we continue to review new lines that have been submitted for NIH’s consideration. Please check the current NIH Human Embryonic Stem Cell Registry page for the most up-to-date list.

    To obtain these cells, please follow the “see details” link, which is found under the Cell Line name, within the NIH Human Embryonic Stem Cell Registry. This link includes more information about the selected cell line, as provided to the NIH. Some of this information may include: whether or not the cell line is available for distribution, the provider’s name, telephone number, email address, and URL.

  2. Who owns the cells?
    The stem cell lines remain the property of the individual stem cell providers, as listed on the NIH Human Embryonic Stem Cell Registry. Researchers may negotiate a material transfer agreement (MTA) with the cell providers in order to specify their rights and responsibilities concerning resulting data, publications, and potential patents.
  3. Are there any restrictions on the use of lines listed on the NIH Human Embryonic Stem Cell Registry?
    The “see details” link on the NIH Human Embryonic Stem Cell Registry includes information on two categories of possible use restrictions: Provider Restrictions and NIH Restrictions. Provider Restrictions include things such as experiments that are prohibited with the cell line, or requirements that proposed research be approved by an ESCRO or other type of ethical review committee. NIH Restrictions are imposed on the use of a line based on the usage of the cells as agreed to by the donors in their informed consent process.

Subclones and Modified hESC Lines

  1. Once a human embryonic stem cell line is listed on the NIH Human Embryonic Stem Cell Registry, are lines derived from it also eligible?
    The NIH Guidelines on Human Stem Cell Research focus on the requirements for donation of the embryo that was used for derivation. Once that determination has been made for a particular line, it applies to all subclones or modifications. For example, now that WA01 (H1) is eligible for NIH funding, WA01 lines that express GFP are also eligible.
  2. Should scientists list the name of the subclone in their NIH grant application?
    Yes, scientists should refer to the parent hESC line and list the cell line name of the modified line or subclone in the research plan of their application.

Research Ethics and Stem Cells

Stem cells show potential for many different areas of health and medical research, and studying them can help us understand how they transform into the dazzling array of specialized cells that make us what we are. Some of the most serious medical conditions, such as cancer and birth defects, are caused by problems that occur somewhere in this process. A better understanding of normal cell development will allow us to understand and perhaps correct the errors that cause these medical conditions.

Research on one kind of stem cell—human embryonic stem cells—has generated much interest and public debate. Pluripotent stem cells (cells that can develop into many different cell types of the body) are isolated from human embryos that are a few days old. Pluripotent stem cell lines have also been developed from fetal tissue (older than 8 weeks of development).

As science and technology continue to advance, so do ethical viewpoints surrounding these developments. It is important to educate and explore the issues, scientifically and ethically.

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