Know more about Stem Cells

 NSC-Reconstruct widely incorporates stem cells in its research programs. For this reason, our projects includes a varied range of activities aimed at communicating stem cell research in close collaboration with the UniStem Centre, the Interdepartmental Centre for Stem Cell Research of University of Milano and EuroStemCell, the European stem cell portal – which provides a broad spectrum of stem cell information. EuroStemCell has specialized content for researchers, accessible resources for non-scientists and award-winning films. Moreover, it has critical analysis of the latest developments in stem cell research.

To help making sense of our research, we provide below an overview on stem cells and their use in research, made available on the website of the International Society for Stem Cell Research (ISSCR), an independent, nonproft organization providing a global forum for stem cell research and regenerative medicine. These resources are also available in a PDF document (download).

What are stem cells?
Stem cells are the foundation cells for every organ and tissue in our bodies. The highly specialized cells that make up these tissues originally came from an initial pool of stem cells formed shortly after fertilization. Throughout our lives, we continue to rely on stem cells to replace injured tissues and cells that are lost every day, such as those in our skin, hair, blood and the lining of our gut. Stem cells have two key properties: 1) the ability to self-renew, dividing in a way that makes copies of themselves, and 2) the ability to differentiate, giving rise to the mature types of cells that make up our organs and tissues.

Tissue-specific stem cells
Tissue-specific stem cells, which are sometimes referred to as “adult” or “somatic” stem cells, are already somewhat specialized and can produce some or all of the mature cell types found within the particular tissue or organ in which they reside. Because of their ability to generate multiple, organ-specific, cell types, they are described as “multipotent.” For example, stem cells found within the adult brain are capable of making neurons and two types of glial cells, astrocytes and oligodendrocytes. Tissue-specific stem cells have been found in several organs that need to continuously replenish themselves, such as the blood, skin and gut and have even been found in other, less regenerative, organs such as the brain. These types of stem cells represent a very small population and are often buried deep within a given tissue, making them difficult to identify, isolate and grow in a laboratory setting.

Embryonic Stem Cells
Embryonic stem cells have been derived from a variety of species, including humans, and are described as “pluripotent,” meaning that they can generate all the different types of cells in the body. Embryonic stem cells can be obtained from the blastocyst, a very early stage of development that consists of a mostly hollow ball of approximately 150-200 cells and is barely visible to the naked eye. At this stage, there are no organs, not even blood, just an “inner cell mass” from which embryonic stem cells can be obtained. Human embryonic stem cells are derived primarily from blastocysts that were created by in vitro fertilization (IVF) for assisted reproduction but were no longer needed. 

The fertilized egg and the cells that immediately arise in the first few divisions are “totipotent.” This means that, under the right conditions, they can generate a viable embryo (including support tissues such as the placenta). Within a matter of days, however, these cells transition to become pluripotent. None of the currently studied embryonic stem cell lines are alone capable of generating a viable embryo (i.e., they are pluripotent, not totipotent). 

Why are embryonic stem cells so valuable?
Unlike tissue-specific (adult) stem cells, embryonic stem cells have the potential to generate every cell type found in the body. Just as importantly, these cells can, under the right conditions, be grown and expanded indefinitely in this unspecialized or “undifferentiated” state. These cells help researchers learn about early human developmental processes that are otherwise inaccessible, study diseases and establish strategies that could ultimately lead to therapies designed to replace or restore damaged tissues.

Induced pluripont stem cells
One of the hottest topics in stem cell research today is the study of induced pluripotent stem cells (iPS cells). These are adult cells (e.g., skin cells) that are engineered, or “reprogrammed,” to become pluripotent, i.e., behave like an embryonic stem cell. While these iPS cells share many of the same characteristics of embryonic stem cells, including the ability to give rise to all the cell types in the body, it is important to understand that they are not identical. The original iPS cells were produced by using viruses to insert extra copies of three to four genes known to be important in embryonic stem cells into the specialized cell. It is not yet completely understood how these three to four “reprogramming” genes are able to induce pluripotency; this question is the focus of ongoing research. In addition, recent studies have focused on alternative ways of reprogramming cells using methods that are safer for use in clinical settings. 

Disease- or patient-specific pluripotent stem cells
One of the major advantages of iPS cells, and one of the reasons that researchers are very interested in studying them, is that they are a very good way to make pluripotent stem cell lines that are specific to a disease or even to an individual patient. Disease-specific stem cells are powerful tools for studying the cause of a particular disease and then for testing drugs or discovering other approaches to treat or cure that disease. The development of patient-specific stem cells is also very attractive for cell therapy, as these cell lines are from the patient themselves and may minimize some of the serious complications of rejection and immunosuppression that can occur following

Moving stem cells into the clinic
Clinical translation is the process used to turn scientific knowledge into real world medical treatments. Researchers take what they have learned about how a tissue usually works and what goes wrong in a particular disease or injury and use this information to develop new ways to diagnose, stop or fix what goes wrong. Before being marketed or adopted as standard of care, most treatments are tested through clinical trials. Sometimes, in attempting new surgical techniques or where the disease or condition is rare and does not have a large enough group of people to form a clinical trial, certain treatments might be tried on one or two people, a form of testing sometimes referred to as innovative medicine. For more information on how science becomes medicine, please visit www.closerlookatstemcells.org.

What is regenerative medicine?
The goal of regenerative medicine is to repair organs or tissues that are damaged by disease, aging or trauma, such that function is restored, or at least improved. The term regenerative medicine is often used nowadays to describe medical treatments and research that use stem cells (either adult or embryonic) to restore the function of organs or tissues. This can be achieved in different ways; first, by administering stem cells, or specific cells that are derived from stem cells in the laboratory; or second, by administering drugs that coax stem cells that are already present in tissues to more efficiently repair the involved tissue.

Current Therapies
Blood stem cells are currently the most frequently used stem cells for therapy. For more than 50 years, doctors have been using bone marrow transplants to transfer blood stem cells to patients, and more advanced techniques for collecting blood stem cells are now being used to treat leukemia, lymphoma and several inherited blood disorders. Umbilical cord blood, like bone marrow, is often collected as a source of blood stem cells and in certain cases is being used as an alternative to bone marrow transplantation. Additionally, some bone, skin and corneal diseases or injuries can be treated by grafting tissues that are derived from or maintained by stem cells. These therapies have also been shown to be safe and effective.

Potential Therapies
Other stem cell treatments, while promising, are still at very early experimental stages. For example, the mesenchymal stem cell, found throughout the body including in the bone marrow, can be directed to become bone, cartilage, fat and possibly even muscle. In certain experimental models, these cells also have some ability to modify immune functions. These abilities have created considerable interest in developing ways of using mesenchymal stem cells to treat a range of musculoskeletal abnormalities, cardiac disease and some immune abnormalities such as graft-versushost disease following bone marrow transplant.

Remaining challenges
Despite the successes we have seen so far, there are several major challenges that must be addressed before stem cells can be used as cell therapies to treat a wider range of diseases. First, we need to identify an abundant source of stem cells. Identifying, isolating and growing the right kind of stem cell, particularly in the case of rare adult stem cells, are painstaking and difficult processes. Pluripotent stem cells, such as embryonic stem cells, can be grown indefinitely in the lab and have the advantage of having the potential to become any cell in the body, but these processes are again very complex and must be tightly controlled. iPS cells, while promising, are also limited by these concerns. In both cases, considerable work remains to be done to ensure that these cells can be isolated and used safely and routinely. Second, as with organ transplants, it is very important to have a close match between the donor tissue and the recipient; the more closely the tissue matches the recipient, the lower the risk of rejection. Being able to avoid the life-long use of immunosuppressants would also be preferable. The discovery of iPS cells has opened the door to developing patient-specific pluripotent stem cell lines that can later be developed into a needed cell type without the problems of rejection and immunosuppression that occur from transplants from unrelated donors. Third, a system for delivering the cells to the right part of the body must be developed. Once in the right location, the new cells must then be encouraged to integrate and function together with the body’s other cells.

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