2008 Amendments to the National Academies' Guidelines for Human Embryonic Stem Cell Research (2008)

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Appendix B Glossary Adult stem cell—An undifferentiated cell found in a differentiated tissue that can renew itself and (with limitations) differentiate to yield the specialized cell types of the tissue from which it originated. Androgenesis—Development in which the embryo contains only paternal chromosomes. Autologous transplant—Transplanted tissue derived from the intended re- cipient of the transplant. Such a transplant helps to avoid complications of immune rejection. Blastocoel—The cavity in the center of a blastocyst. Blastocyst—A preimplantation embryo of 50–250 cells depending on age. The blastocyst consists of a sphere made up of an outer layer of cells (the trophectoderm), a fluid-filled cavity (the blastocoel), and a cluster of cells on the interior (the inner cell mass). Blastomere—A single cell from a morula or early blastocyst, before the dif- ferentiation into trophectoderm and inner cell mass. Bone marrow—The soft, living tissue that fills most bone cavities and con- tains hematopoietic stem cells, from which all red and white blood cells evolve. The bone marrow also contains mesenchymal stem cells from which a number of cell types arise, including chondrocytes, which produce cartilage, and fibroblasts, which produce connective tissue. N     ew or modified wording is indicated by underlining, deleted text by strikeout. 39 

40 Appendix B Chimera—An organism composed of cells derived from at least two ge- netically different cell types. The cells could be from the same or separate species. Differentiation—The process whereby an unspecialized early embryonic cell acquires the features of a specialized cell, such as a heart, liver, or muscle cell. DNA—Deoxyribonucleic acid, a chemical found primarily in the nucleus of cells. DNA carries the instructions for making all the structures and materi- als the body needs to function. Ectoderm—The outermost of the three primitive germ layers of the embryo; it gives rise to skin, nerves, and brain. Egg cylinder—An asymmetric embryonic structure that helps to determine the body plan of the mouse. Electroporation—Method of introducing DNA into a cell. Embryo—An animal in the early stages of growth and differentiation that are characterized by cleavage, laying down of fundamental tissues, and the formation of primitive organs and organ systems; especially the developing human individual from the time of implantation to the end of the eighth week after conception, after which stage it becomes known as a fetus. Embryoid bodies (EBs)—Clumps of cellular structures that arise when em- bryonic stem cells are cultured. Embryoid bodies contain tissue from all three germ layers: endoderm, mesoderm, and ectoderm. Embryoid bodies are not part of normal development and occur only in vitro. Embryonic disk—A group of cells derived from the inner cell mass of the blastocyst, which later develops into an embryo. The disk consists of three germ layers known as the endoderm, mesoderm, and ectoderm. Embryonic germ (EG) cells—Cells found in a specific part of the embryo or fetus called the gonadal ridge that normally develop into mature gametes. The germ cells differentiate into the gametes (oocytes or sperm). http://www.nlm.nih.gov/medlineplus/mplusdictionary.html. In common parlance, “em- bryo” is used more loosely and variably to refer to all stages of development from fertilization until some ill-defined stage when it is called a fetus. There are strictly defined scientific terms such as “zygote,” “morula,” and “blastocyst” that refer to specific stages of preimplantation development (see Chapter 2 of NRC and IOM, 2005). In this report, we have used the more precise scientific terms where relevant but have used the term “embryo” where more precision seemed likely to confuse rather than clarify. 

Appendix B 41 Embryonic stem (ES) cells—Primitive (undifferentiated) cells derived from the early embryo that have the potential to become a wide variety of special- ized cell types. Endoderm—Innermost of the three primitive germ layers of the embryo; it later gives rise to the lungs, liver, and digestive organs. Enucleated cell—A cell whose nucleus has been removed. Epidermis—The outer cell layers of the skin. Epigenetic—Refers to modifications in gene expression that are controlled by heritable but potentially reversible changes in DNA methylation or chro- matin structure without involving alteration of the DNA sequence. Epithelium—Layers of cells in various organs, such as the epidermis of the skin or the lining of the gut. These cells serve the general functions of protection, absorption, and secretion, and play a specialized role in moving substances through tissue layers. Their ability to regenerate is excellent; the cells of an epithelium may replace themselves as frequently as every 24 hours from the pools of specialized stem cells. Feeder cell layer—Cells that are used in culture to maintain pluripotent stem cells. Feeder cells usually consist of mouse embryonic fibroblasts. Fertilization—The process whereby male and female gametes unite to form a zygote (fertilized egg). Fibroblasts—Cells from many organs that give rise to connective tissue. Gamete—A mature male or female germ cell, that is, sperm or oocyte, respectively. Gastrulation—The procedure by which an animal embryo at an early stage of development produces the three primary germ layers: ectoderm, mesoderm, and endoderm. Gene—A functional unit of heredity that is a segment of DNA located in a specific site on a chromosome. A gene usually directs the formation of an enzyme or other protein. Gene targeting—A procedure used to produce a mutation in a specific gene. Genital ridge—Anatomic site in the early fetus where primordial germ cells are formed. Genome—The complete genetic material of an organism. 

42 Appendix B Genotype—Genetic constitution of an individual. Germ cell—A sperm or egg or a cell that can become a sperm or egg. All other body cells are called somatic cells. Germ layer—In early development, the embryo differentiates into three dis- tinct germ layers (ectoderm, endoderm, and mesoderm), each of which gives rise to different parts of the developing organism. Germ line—The cell lineage from which the oocyte and sperm are derived. Gonadal ridge—Anatomic site in the early fetus where primordial germ cells (PGCs) are formed. Gonads—The sex glands—testis and ovary. Hematopoietic—Blood-forming. Hematopoietic stem cell (HSC)—A stem cell from which all red and white blood cells evolve and that may be isolated from bone marrow or umbilical cord blood for use in transplants. Hepatocyte—Liver cell. Heterologous—From genetically different individuals. hES cell—Human embryonic stem cell; a type of pluripotent stem cell. Histocompatibility antigens—Glycoproteins on the surface membranes of cells that enable the body’s immune system to recognize a cell as native or foreign and that are determined by the major histocompatibility complex. Homologous recombination—Recombining of two like DNA molecules, a process by which gene targeting produces a mutation in a specific gene. hPS cells—Human pluripotent stem cells derived from non-embryonic sources. Hybrid—An organism that results from a cross between gametes of two different genotypes. Immune system cells—White blood cells, or leukocytes, that originate in the bone marrow. They include antigen-presenting cells, such as dendritic cells, T and B lymphocytes, macrophages, and neutrophils, among many others. Immunodeficient mice—Genetically altered mice used in transplantation experiments because they usually do not reject transplanted tissue. Immunogenic—Related to or producing an immune response. 

Appendix B 43 Immunosuppressive—Suppressing a natural immune response. Implantation—The process in which a blastocyst implants into the uterine wall, where a placenta forms to nurture the growing fetus. Inner cell mass—The cluster of cells inside the blastocyst that give rise to the embryonic disk of the later embryo and, ultimately, the fetus. Interspecific—Between species. In utero—In the uterus. In vitro—Literally, “in glass,” in a laboratory dish or test tube; in an artificial environment. In vitro fertilization (IVF)—An assisted reproductive technique in which fertilization is accomplished outside the body. In vivo—In the living subject; in a natural environment. Karyotype—The full set of chromosomes of a cell arranged with respect to size, shape, and number. Leukemia inhibitory factor (LIF)—A growth factor necessary for maintaining mouse embryonic stem cells in a proliferative, undifferentiated state. Mesenchymal stem cells—Stem cells found in bone marrow and elsewhere from which a number of cell types can arise, including chondrocytes, which produce cartilage, and fibroblasts, which produce connective tissue. Mesoderm—The middle layer of the embryonic disk, which consists of a group of cells derived from the inner cell mass of the blastocyst; it is formed at gastrulation and is the precursor to bone, muscle, and connective tissue. Morula—A solid mass of 16–32 cells that resembles a mulberry and results from the cleavage (cell division without growth) of a zygote (fertilized egg). Mouse embryonic fibroblast (MEF)—Cells used as feeder cells in culturing pluripotent stem cells. Multipotent—Capable of differentiation into a limited spectrum of differ- entiated cell types. Neural stem cell (NSC)—A stem cell found in adult neural tissue that can give rise to neurons, astrocytes, and oligodendrocytes. Nuclear transfer (NT)—Replacing the nucleus of one cell with the nucleus of another cell. 

44 Appendix B Oocyte—Developing egg; usually a large and immobile cell. Ovariectomy—Surgical removal of an ovary. Parthenogenesis—Development in which the embryo contains only maternal chromosomes. Passage—A round of cell growth and proliferation in culture. Phenotype—Visible properties of an organism produced by interaction of genotype and environment. Placenta—The oval or discoid spongy structure in the uterus from which the fetus derives its nourishment and oxygen. Pluripotent cell—A cell that has the capability of developing into cells of all germ layers (endoderm, ectoderm, and mesoderm). Precursor cells—In fetal or adult tissues, partly differentiated cells that divide and give rise to differentiated cells. Also known as progenitor cells. Preimplantation genetic diagnosis (PGD)—A procedure applied to IVF em- bryos to determine which ones carry deleterious mutations predisposing to hereditary diseases. Primary germ layers—The three initial embryonic germ layers—endo- derm, mesoderm, and ectoderm—from which all other somatic tissue types develop. Primordial germ cell—A cell appearing during early development that is a precursor to a germ cell. Primitive streak—The initial band of cells from which the embryo begins to develop. The primitive streak establishes and reveals the embryo’s head-tail and left-right orientations. Pseudopregnant—Refers to a female primed with hormones to accept a blastocyst for implantation. Somatic cell—Any cell of a plant or animal other than a germ cell or germ cell precursor. Somatic cell nuclear transfer (SCNT)—The transfer of a cell nucleus from a somatic cell into an egg (oocyte) whose nucleus has been removed. Stem cell—A cell that has the ability to divide for indefinite periods in vivo or in culture and to give rise to specialized cells. 

Appendix B 45 Teratoma—A tumor composed of tissues from the three embryonic germ layers. Usually found in ovary or testis. Produced experimentally in animals by injecting pluripotent stem cells to determine the stem cells’ abilities to differentiate into various types of tissues. Tissue culture—Growth of tissue in vitro on an artificial medium for experi- mental research. Transfection—A method by which experimental DNA may be put into a cultured cell. Transgene—A gene that has been incorporated into a cell or organism and passed on to successive generations. Transplantation—Removal of tissue from one part of the body or from one individual and its implantation or insertion into another, especially by surgery. Trophectoderm—The outer layer of the developing blastocyst that will ulti- mately form the embryonic side of the placenta. Trophoblast—The extraembryonic tissue responsible for negotiating implan- tation, developing into the placenta, and controlling the exchange of oxygen and metabolites between mother and embryo. Undifferentiated—Not having changed to become a specialized cell type. Xenograft or xenotransplant—A graft or transplant of cells, tissues, or organs taken from a donor of one species and grafted into a recipient of another species. Zygote—A cell formed by the union of male and female germ cells (sperm and egg, respectively).