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Regenerative Medicine (RM) is a branch of translational research in tissue engineering and molecular biology which deals with the “process of replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function”.
A stem cell is an undifferentiated cell of a multicellular organism that is capable of giving rise to indefinitely more cells of the same type, and from which certain other kinds of cell arise by differentiation.
Human Umbilical Cord Tissue—human umbilical cord tissue is a rich source of mesenchymal stem cells. Umbilical cord tissue-derived cells are best suited for tissue regeneration due to the tissue repairing function of the mesenchymal stem cells. They are also well-suited for immune system modulation and reducing inflammation.
Bone Marrow—bone marrow-derived stem cells provide support for tissue regeneration via revascularization properties and their ability to support mesenchymal stem cells in the body.
Cord Blood—Most protocols using cord blood require Human leukocyte antigen (HLA) typing to match the recipient and donor. Like bone marrow, cord blood is source of CD34+ stem cells (but a poor source of mesenchymal stem cells). These stem cells provide support for tissue regeneration via revascularization properties and their ability to support mesenchymal stem cells in the body.
Adipose (fat) Tissue—adipose tissue is a rich source of mesenchymal stem cells (MSCs) and T-regulatory cells which modulate the immune system. Adipose-derived cells can be used for treating systemic autoimmune and inflammatory conditions. They also play a role in regenerating injured tissue.
Platelet-rich plasma is a concentrate of platelet-rich plasma protein derived from whole blood, centrifuged to remove red blood cells.
Concentrated bone marrow aspirate (BMA) is a biologic concentrate derived from a patient’s own bone marrow. Concentrated BMA is high in mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs), which are known to be critical in biological processes such as tissue regeneration and bone formation.
Adipose stem cells (ASCs) are an attractive and abundant stem cell source with therapeutic applicability in diverse fields for the repair and regeneration of acute and chronically damaged tissues.
Alpha-2-Macroglobulin is a large plasma protein found in the blood. It is mainly produced by the liver, and also locally synthesized by macrophages, fibroblasts, and adrenocortical cells. In humans it is encoded by the A2M gene.
Amniotic Fluid—amniotic fluid is the protective liquid contained by the amniotic sac of a gravid Amniote. Thisfluid serves as a cushion for the growing fetus, but also serves to facilitate the exchange of nutrients, water, and biochemical products between mother and fetus.
Whartons Jelly—Wharton’s jelly (substantia gelatinea funiculi umbilicalis) is a gelatinous substance within the umbilical cord also present in vitreous humor of the eyeball, largely made up of mucopolysaccharides (hyaluronic acid and chondroitin sulfate). It also contains some fibroblasts and macrophages. It is derived from extra-embryonic mesoderm. Cells in Wharton’s jelly express several stem cell genes, including telomerase. They can be extracted, cultured, and induced to differentiate into mature cell types such as neurons. Wharton’s jelly is therefore a potential source of adult stem cells (also see the more common method of storing cord blood). Wharton’s jelly-derived mesenchymal stem cells may have immunomodulatory effect on lymphocytes. In a recent study, Wharton’s Jelly tissue transplantation has shown to be able to reduce traumatic brain injury and may have therapeutic potential.
Placental Membranes—the placental membrane separates maternal blood from fetal blood. The fetal part of the placenta is known as the chorion. The maternal component of the placenta is known as the decidua basalis.
Cord Blood—cord blood is blood that remains in the placenta and in the attached umbilical cord after childbirth. Cord blood is collected because it contains stem cells, which can be used to treat hematopoietic and genetic disorders
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.
Stem cells may be pluripotent or multipotent.
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 (including adult and umbilical cord blood) 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.
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.
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 revulutionize 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.
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. Please refer to Basic Questions FAQ #3, above.
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.”
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.
Stem cell research offers hope for treating many human diseases. Click here to read a description of the current status of stem cells and human disease therapies.
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.
The public may search a database of NIH-sponsored clinical trials at www.clinicaltrials.gov. Enter the search terms of interest (in this case, Parkinson’s Disease and stem cells) to search for applicable clinical trials.
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 at http://bethematch.org/support-the-cause/donate-cord-blood/how-to-donate-cord-blood/.