Adult stem cell: Tissue-specific stem cells. A stem cell found in fetal and/or adult tissues that typically generates the type of tissue in which it is found (blood stem cells make blood, neural stem cells make neurons, and so forth).
Autologous: Cells or tissue obtained from the patient. Sometimes a patient will have a portion of her own tissues stored for therapeutic use later. Examples include privately banked umbilical cord blood or a patient’s own bone marrow that is stored prior to receiving chemotherapy for solid tumors. The patient’s own marrow may then be transplanted at a later date to “rescue” the person from the side effects of chemotherapy on her blood system.
Blastocyst: The four-to-nine day-old embryo (post-fertilization) which consists of 100-200 total cells and is approximately 1/10 of a millimeter in diameter (roughly the size of a period at the end of this sentence). This stage of development is prior to implantation in the uterus. Only two types of cells are present at this time, the trophectoderm (foundation of the placenta) and the inner-cell mass or ICM, which will also contribute cells to the extraembryonic tissues as well as the entire fetus. The blastocyst looks like a hollow, fluid-filled ball of trophectodermal cells where the ICM forms a slight lump on the inner wall. It is from this developmental stage that the vast majority of embryonic stem cells are obtained.
Blastomeres: The earliest cleavage stages of the embryo. The fertilized egg (zygote) cleaves to make two cells termed blastomeres which in turn cleave to make four and so on. The blastomeres are no longer called such at the morula stage of pre-implantation development. Blastomeres are totipotent as removal of one blastomere may create an identical twin in vivo.
Bone marrow: The spongy tissue that fills most long bone cavities and contains hematopoietic stem cells. The bone marrow also contains other cell types such as mesenchymal stem cells, endothelial (vascular) cells, macrophages (debris clearing cells), and more.
Cell line: A culture of related cells. A single embryo may be used to produce a line (or population) of cells that are genetically identical to one another as they divide and create a larger population. Two different cell lines originate from two different embryos. Cell lines may be expanded (i.e. put into cell culture to make greater numbers of them), frozen, and/or shared with other scientists. Thus, a single cell line may be simultaneously cultured in laboratories around the world as it is maintained and shared by different scientists.
Chimera: An organism made up of two genetically distinct types of cells from the same or different species. Though not often used as a descriptive term today, the clinical transplant recipient was once referred to as being “chimeric,” because following the recipient’s therapy, her body contains cells from two different individuals: her own and the cells donated to her for therapy. Embryos may also be chimeras when cells are combined at the earliest stages of development. The creation of mouse chimeras is a common (though powerful) research tool that permits the study of cells in different environments. A chimera is not the same as a hybrid.
Cloning: The process of making identical genetic copies. In the laboratory, cloning is used to create pure stocks of many types of organisms from bacteria to plants. In the field of ES cell research, cloning most often broadly refers to creating genetically identical cells (see entries for Somatic cell nuclear transfer and Therapeutic cloning) or entire organisms (see entry for Reproductive cloning).
Cord blood stem cells: Blood stem cells obtained from the umbilical cord and placenta following the birth of a child. While at this point in time cord blood is only a source of cells for use in hematopoietic transplantation, research is underway to identify and use other cell types present in this tissue such as mesenchymal or endothelial (blood vessel) stem cells.
Differentiation: The maturation process of primitive cells into the specialized, functional cell types of the body such as when the blood stem cell produces red cells, white cells, and platelets. (See also Transdifferention)
Embryo: The earliest stages of vertebrate (animals with a backbone) development. Most often describes the stages from fertilization through implantation into the wall of the uterus, and extending to the eighth week of pregnancy. Some definitions describe the embryonic stage as spanning from implantation to the eighth week with the earliest stages termed “pre-implantation.”
Embryoid body: EB. An aggregation of differentiating ES cells in vitro (10,000-30,000 cells per EB). EBs do not occur naturally and are merely a type of cell culture procedure used in the laboratory to permit the study of cellular maturation.
Embryonic stem cell: ES cell. A cell derived from the inner cell mass of the pre-implantation blastocyst (around five to seven days post-fertilization in humans) that is pluripotent and capable of self-renewal in cell culture.
Epigenetic: Literally, “upon the genome.” Chemical modifications of DNA that do not alter a gene’s sequence, but impact gene expression and may also be inherited. Epigenetic modifications to DNA are very important to both imprinting and cellular reprogramming.
Feeder cells: A convenient way to grow ES cells in the laboratory is via co-culture with feeder cells. The feeders, typically mouse embryonic fibroblasts or human fibroblasts, secrete growth factors, hormones, and other proteins that keep ES cells alive as well as prevent them from differentiating.
Germ layer: The most primitive level of tissue organization. In development, there are three embryonic germ layers and one extraembryonic germ layer. The embryonic germ layers are: endoderm (gut tissue), mesoderm (including blood, bone, and muscle), and ectoderm (such as skin and nerve). The extraembryonic germ layer is trophectoderm and is not found in the adult organism.
Graft rejection: When donated cells, tissues, or organs are rejected by the patient’s body. The risk of graft rejection can be lessened by immunosuppression though this treatment often causes long-term complications.
Graft-versus-host disease: GvHD. When the donated cells reject the body of the transplant recipient. While GvHD may be lessened by immunosuppression, this treatment often causes long-term complications.
Histocompatibility: The degree of genetic matching between tissues or cells from a donor and a transplant recipient. The most important genes for tissue matching are HLA-A, HLA-B, and HLA-DR. People get one copy of each of these genes from each parent (three from mom and three from dad), so a person has six places to match for histocompatibility. Thus, a “full match” in transplantation is called a 6 on 6 or 6/6 due to correct matching at both the maternal and paternal copies of HLA-A, HLA-B, and HLA-DR. The lower the degree of matching at these genes, the more likely it is that a transplant will fail. For the most part, a child will only match half of their HLA genes to one or the other parent (3/6). Thus, parents are most often not nearly as compatible to be transplant donors to their children as are the child’s siblings, who in rare cases, can match perfectly to one another (6/6).
Immunosuppression: The use of powerful drugs to impair a patient’s immune system in order to prevent the rejection of transplanted tissues or GvHD. Long-term immunosuppression may lead to liver damage, cataracts, and/or infections, among other problems.
In vitro fertilization (IVF): A procedure where an egg cell (the oocyte) and sperm cells are brought together outside of the body in a dish (i.e. in vitro), so that a sperm cell can fertilize the egg. The resulting fertilized egg, called a zygote, will start dividing and after a several divisions, form the embryo that can be implanted into the womb of a woman and may give rise to pregnancy. The first child resulting from successful IVF was born in the United Kingdom in 1978.
Induced pluripotent cell (iPS): a type of pluripotent cell made directly from a somatic (from the body) cell. First achieved using mouse cells by Shinya Yamanaka of Japan in 2006, the technique has successfully been used to “reprogram” human somatic cells to a state very similar to ES cells. The iPS process uses three genes (Oct4, Nanog, and Sox2) with an occasional fourth (c-Myc) that are introduced to cells using viruses. Non-viral methods are under development.
IRB: Institutional Review Board, the institutional committee charged with reviewing research proposals to ensure that important rights and protections are afforded to persons participating in research.
Morula: This is the stage of preimplantation embryonic development between the cleaving blastomeres and the blastocyst and numbering less that 32 cells. At this stage, it is very difficult to discern individual cells within the embryo.
Multipotent: A degree of developmental versatility that is less than totipotent and pluripotent. Multipotent means a stem cell may form many types of cells in a given lineage, but not cells of other lineages. For example, a multipotent blood stem cell can form the many different types of blood cells (red, white, platelets, etc.), but it cannot form neurons. Most adult or tissue-specific stem cells are multipotent.
Neural stem cell: A type of stem cell that resides in the brain that can make new nerve cells (neurons) and other cells that support nerve cells (glia). In the adult, neural stem cells can be found in very specific areas of the brain where replacement of nerve cells is seen.
Nuclear transfer: Also known as somatic cell nuclear transfer (SCNT), therapeutic cloning, research cloning, or cellular cloning. The process of removing and discarding the nucleus which contains the genetic material from one cell and replacing it with the intact nucleus of another.
Passage: The step during cell culture where a dish of cells has become sufficiently populated (as they are dividing) and it must be expanded or “split” into more dishes. If stem cells become too crowded, they get “stressed,” stop growing as pristine, undifferentiated stem cells, and begin to differentiate in an uncontrolled fashion. Thus, regular passaging helps maintain pristine stem cell cultures for use in experiments.
Plasticity: The ability to morph from one cell type into another. For example, from a mesenchymal (connective tissue) stem cell into an osteoblast (a bone progenitor cell) or hypothetically, from a neuron into a blood cell.
Pluripotent: The potential of a stem cell that describes an ability to differentiate into all types of specialized cell in the body. Scientifically, a cell is termed pluripotent if it is capable of making derivatives of all three embryonic (basic) germ layers: endoderm (gut tissue), mesoderm (including blood, muscle, and vessels), and ectoderm (such as skin and nerve).
Primitive streak: A furrow in the developing embryo that begins to form a few weeks after fertilization and is the first sign that body polarity is being established (left to right, head to tail, front to back). It is arguably the first robust sign that a degree of organismal integration is present that is needed to continue on in development.
Progenitor cell: A primitive yet somewhat more mature cell than a stem cell. A progenitor cell has less of a capacity to self-renew than a stem cell. Progenitors are cells at a stage in between stem cells and mature, functional cells.
Self-renewal: The ability of stem cells to generate new, functionally identical copies of themselves. If stem cells could not self-renew, tissues would run out of replacement cells for those lost due to damage and decay.
Somatic cell nuclear transfer: SCNT. The process wherein the genetic material of one cell is replaced with that of another. Typically, when used to make ES cells, the donated nucleus comes from a somatic cell, like a skin cell, and the recipient is an egg whose own DNA-containing nucleus has been removed. When the egg has received the donated nucleus, it is said to be “reconstituted.” It may then be induced to begin dividing and the resulting embryo may then be used to make new ES cells.
Teratoma: A benign tumor that forms from abnormal germ cells. Teratomas may also be formed from other, normal pluripotent cells such as embryonic stem cells and iPS cells when these cells are injected into immunodeficient mice. The formation of these experimentally-produced teratomas indicates how developmentally robust the pluripotent cell line is.
Tissue Engineering: The use of cells and biomaterials (such as degradable matrices and scaffolds) to generate tissues. Examples are mini, implantable bioreactors that contain liver cells and like the liver, may remove toxins from the circulation.
Totipotent: Capable of making all of the cells in the adult body as well as the extraembryonic tissues including the placenta. The fertilized egg (zygote) is totipotent as are the early cleaved cells (blastomeres).
Transdifferentiation: This is a poorly-understood process wherein a cell from one type of lineage (such as muscle) appears to morph into a cell of another type (such as blood). It is unknown whether or not this occurs in the normal course of biology (many feel that it does not). Nevertheless, cells may be capable of being engineered to create patient-matched tissues of various types. This is not the same as “transprogramming.”
Zona pellucida: The hard shell around the nascent embryo that protects multiple sperm from entering at fertilization and that also protects the embryo as it travels down the fallopian tube on the way to uterine implantation. The zona would prohibit implantation of the embryo and so it is shed just prior to implantation in a process known as “hatching”.