Regenerative & Stem Cells
FAQs: Stem Cells
Frequently Asked Questions (FAQs) about Stem Cells
Revised and partially excerpted from https://stemcells.nih.gov/info/pages/faqs.aspx and
International Society for Stem Cell Research (ISSCR) link https://www.closerlookatstemcells.org
Basic Science FAQs
What are stem cells?
Stem cells are cells that have the potential to replicate and are not specialized to final differentiation. That is, they can develop into some or many different cell types in the body, depending on whether they are totipotent, pluripotent or multipotent. Totipotent stem cells are found in the early embryo whereas pluripotent and multipotent cells are found in the embryo through adult life. The stem cells play a critical role in tissue and organ development and in a body’s self-repair. Either direct induction of a stem cell into a differentiated cell and/or from the stem cells providing a repair function, such as releasing cytokines or other chemical mediators that recruit other cells to repair a damaged tissue or organ site.
More details are at https://stemcells.nih.gov/info/basics/Pages/Default.aspx on the NIH website Stem Cell Basics which provides basic information about stem cells. Further discussions are available from the NIH stem cell reports at https://stemcells.nih.gov/info and in the extensive literature found online at PubMed.
What are “adult stem cells” and how are they different from “embryonic stem cells” (ESCs)?
Adult stem cells (also termed somatic stem cells) are undifferentiated multipotent or pluripotent stem cells that reside in a specific area of each tissue or organ (i.e., a “stem cell niche”). They may remain quiescent (non-dividing) until they are activated by a normal need for more cells, e.g., due to disease or tissue injury. Also, as part of that activation process they may release factors that stimulate recruitment of other cells to migrate to the repair site. Adult stem cells are defined by their somatic tissue or organ site, whereas ESCs are defined by their early embryonic origin.
What are the classes of stem cells and where do they come from?
Stem cells may be classified as totipotent (equivalent to omnipotent), pluripotent or multipotent. All are able to replicate. In historical work, only the totipotent cells were referred to as “stem cells”, with pluripotent and multipotent cells generally called “progenitor cells”. However, definitions have changed. All classes can be found in developing embryos, with “adult stem cells” classed as pluripotent or multipotent.
- Totipotent stem cells, are embryonic stem cells (ESCs) from the early embryonic development stages. They can replicate and differentiate into any cell type.
- Pluripotent stem cells are fetal to adult stem cells that can theoretically give rise to any type of cell in the body except those needed to support and develop a fetus in the womb.
- Multipotent stem cells are fetal to adult stem cells that can give rise only to a small number of different cell types, usually within a specific organ site. There is typically only 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.
What happens after a stem cell is activated and divides?
When a stem cell is activated and divides, each “daughter” cell has the potential to either remain a stem cell or to differentiate and become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell. The cell may also then begin releasing cytokines, chemokines or other factors that stimulate growth, differentiation and/or migration of other cells at the local site or from elsewhere in the body to migrate to the site. Control of differentiation is based on the cell’s indigenous genetic programming and the bidirectional molecular, chemical and physical signaling between the cell and its tissue environment.
What are induced pluripotent stem cells (iPSCs)?
These are adult multipotent stem cells that are genetically reprogrammed to induce an embryonic stem cell–like state by being forced to express genes and factors important to maintain the defining properties of ESCs, including differentiation into all three germ layers: the endoderm, mesoderm and ectoderm. The genetic reprogramming is done by nucleic acids and specialized delivery systems or by viruses carrying the targeted genetic information. The cells can then be further manipulated to become specific cell types of interest, which have potential research and clinical uses.
Importantly, this allows the creation of research tools and pre-clinical, drug-screening test cells for various differentiated cell types from the same donor and the same differentiated cell types from multiple donors.
It also would potentially allow cell-based therapies for self-replacement of certain cell types using easily obtained donor cells (e.g., skin, fat, peripheral blood), and without the need for immunosuppressive therapy, since the cells would be autologous (self). There are iPSC clinical studies underway, but the fact that the cells are more embryo-like and also tumor-like have invoked safety concerns that need to be addressed based on the proposed clinical application and the recipient patient population.
Example of iPSCs Manufacturing and Use from Figure 1 of an Open Access Review Publication: A. Tanaka, S. Yuasa,*, K. Node, K. Fukuda. Cardiovascular Disease Modeling Using Patient-Specific Induced Pluripotent Stem Cells. Int. J. Mol. Sci. 2015, 16(8), 18894-18922; doi:10.3390/ijms160818894
Flowchart of potential applications of patient-specific induced pluripotent stem cell (PS-iPSC) systems. Somatic cells derived from patients with genetic disorders are reprogrammed into a pluripotent state, that is, iPSCs, via induction of defined transcription factors. Subsequently, disease-relevant or mutation-corrected cells are differentiated from iPSCs by gene targeting techniques. Purified and expanded cells are potentially utilized in cellular transplantations. Conversely, differentiated cells can be applied to in vitro analyses such as disease modeling and drug testing. In disease modeling, cellular phenotypes are characterized through various experimental methods, potentially providing novel clues to the underlying disease mechanisms, which may further lead to the development of therapeutic strategies. Based on the cellular characteristics, candidate chemical compounds can be evaluated for drug efficacy and toxicity. In the future, PS-iPSC systems could be a useful platform in personalized medicine and efficient drug discovery in collaboration with the drug-manufacturing industry. MEA, multi-electrode array; PS-iPSC, patient specific-induced pluripotent stem cell.
Clinical Use FAQs
Results from clinical studies and on-going clinical studies can be found on the NIH website: www.clinicaltrials.gov
Why can’t the body repair itself the same way it naturally does for skin, bones and muscles?
We know that the body seems to have continuous types of repair processes ongoing throughout life, but major incremental changes and end-stage functional differentiation vary with tissue and organ type. At this time, we do not totally understand how repair is controlled at the molecular, cellular, tissue, organ and organism levels. Scientific work has shown that the regulatory pathways for various lineages of cell growth, differentiation, etc. are modulated by the micro- and macro-environments. There are differences in the cell-associated markers or receptors that characterize or control growth and differentiation of cells from the various organ sites. Many cellular controls for growth and differentiation are known, but the ability to reproducibly harness and regulate them along specific pathways is still elusive to most medical care and applications.
Have stem cells been successfully used to treat medical conditions and specific diseases?
Yes. Blood stem cells have been used for more than 50 years and are currently the most commonly used stem cells. Bone marrow transplants have historically been used by physicians to transfer blood stem cells to patients. Those methods, and more advanced techniques for collecting blood stem cells are now being used to treat leukemia, lymphoma and several inherited blood disorders. Another source of blood stem cells is umbilical cord blood and, even though the cell numbers are low there have been transplant successes and use of cord blood as an alternative source to bone marrow. In addition, certain grafted tissues that are derived from, or maintained by, stem cells or stem cell factors are providing therapies for injuries and certain diseases.
Where can I find more information on bone marrow and cord blood donations and transplants?
The National Marrow Donor Program https://bethematch.org/ website and its Web page on donating cord blood at https://bethematch.org/support-the-cause/donate-cord-blood/how-to-donate-cord-blood.
I have Parkinson’s Disease. Is there a clinical trial that I can participate in that is using stem cells as a therapy?
The public may search a database of NIH-sponsored clinical trials at www.clinicaltrials.gov. Enter the terms of interest (in this case, Parkinson’s Disease and stem cells) to search for applicable clinical trials.
How can I know if allogeneic donor stem cells or my own autologous stem cells would be a better choice to treat my clinical condition? Or, should I wait for iPSCs to be developed for me?
Currently, the numbers and types of clinical conditions with approved stem cell therapies are limited, with even fewer for iPSCs. Many uses for stem cell therapies, including iPSCs, are being investigated and the benefits and risks are not known yet. If you have a qualified doctor who has determined that your disease can potentially be treated with stem cells or that you may be eligible for a clinical study, then it is likely that use of your own cells rather than a donor’s cells may be undesirable or may not be known. On the positive side, your body would be less likely to reject or respond immunologically to your own cells, but that would depend on how they are prepared or manipulated and what they would be expected to do after being transplanted. However, if you are older and if you have a disease, then your own cells may not provide therapeutic benefit and may even be a risk, for example if you have cancer. Also, a clinical study for which you are eligible may have cell therapy from an allogeneic donor source. In that case, there may be some matching and/or immune suppression needed to assure that your body would accept the cells. Alternatively, cells that are less likely to cause an immune response, such as mesenchymal stem cells, may be proposed for use.
Should I store my stem cells for potential future use? If so, what types of cells should be stored?
Storing stem cells is a personal choice for a donor or donor family. This is true whether or not the cells are from an adult or are “adult stem cells” taken at birth (e.g., as umbilical cord blood or tissue). If that is the choice, you want the cells to be as young and robust as possible. Therefore, you would want to do it earlier rather than later. Because you cannot predict the potential use of the cells, it is difficult to decide whether or not to store stem cells from blood (hematopoietic) or from alternate tissues such as cord, fat or skin. Stem cells and progenitor cells specific to a tissue are in very small numbers in all organ sites where their presence has been defined. Thus their later use may require culture and in vitro expansion to achieve therapeutic numbers.
How are stem cells harvested from blood?
Stem cells from blood are usually enriched by “calling up” cells from the bone marrow using specific growth factors. The patient is pre-treated, and several days later blood is collected. The cells are separated from the blood plasma, then further purified using a variety of separation and purification methods.
How are stem cells harvested from tissues?
Solid tissues, including fat, skin or bone marrow, are obtained by surgical procedures and handled using sterile procedures throughout processing. The tissues are treated with enzymes or other factors to release cells from one another and from the tissue matrix that holds them in place in the tissue. Although this is a lot of manipulation, many of the techniques have been developed and improved over many years. Most importantly, the cell numbers and cell viability are critical to having a quality cell product.
Where and how are stem cells stored, what are the costs and what is guaranteed?
Cells are kept in specialized freezers at qualified cell and tissue banks, sometimes called “Bio-Banks”. The storage facility should be properly registered and qualified. The isolated or enriched population of stem cells are mixed in a sterile cryostorage solution, counted to assess cell numbers and viability, put into labeled cryovials or cryobags, then placed under conditions for freezing to proceed at about (-)1 degree per minute. After the cells are frozen they are inventories and transferred for long-term storage. Temperatures are kept at or below -120°C, so most storage is done in the vapor phase of a liquid nitrogen-containing storage freezer. There will be fees associated with collection, processing and storage. These are variable with storage fees averaging about $300 per year. Theoretically they can be stored indefinitely but storage will have a designated time period. There are no guarantees for the potential clinical use of the cells.
Who owns stem cells and stem cell technologies?
You own your own stem cells and can elect for their autologous use in concert with your physician, within the limits of medical practice and regulatory aspects related clinical use. You would also own your re-programmed iPSCs if they were available. Allogeneic donor stem cells, which may come from living or cadaver donors according to tissue procurement practices and laws, are processed from tissues, then manufactured and stored. They are owned by the manufacturer, but then are owned by the patient after transplantation. Some technologies related to stem cells may be patented. For information on patents, 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.”
Are tumor cells stem cells?
Some tumor cells or subsets of cells in a tumor may be tumor stem cells. That is, the cells are able to replicate and some may be able to differentiate into various cell lineages. Also, tumor cells commonly express fetal or developmental cellular and tissue antigens.