HyStem™ Cell Culture

HyStem Glossary of Terms

A  |  B  |  C  |  D  |  E  |  F  |  G  |  H  |  I  |  L  |  M  |  N  |  O  |  P  |  R  |  S  |  T  |  U


A

Acinus (plural: acini) - The word comes from the latin word “grape”. It refers to the sac-like termination of a secretary exocrine gland. In vitro, mammary epithelial cells cultured in a laminin-rich matrix form acinus-like spheres.

Adult (or somatic) stem cell - Stem cells found in specific adult organs or tissues which can differentiate into specialized cell types within that organ or tissue. For example, a cancer stem cell can give rise to differentiated tumor cells. Adult stem cells are multipotent and hence can only differentiate into cells found in their own tissue of origin.

Astrocyte - A glial, neuron-supporting cell.

Allogeneic transplantation- Transplantation of cells, tissues, or organs between individuals of same species. For example, a kidney transplant from one donor to another recipient.

Autologous transplantation - Transplantation of cells, tissues, or organs within the same individual. For example, using a patient’s patellar tendon for anterior cruciate surgery reconstruction.

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B

Basement membrane - The basement membrane (BM) is a thin layer of extracellular matrix that forms between the epithelia and endothelia. It surrounds muscle, fat and nerve cells. It provides mechanical structure, separates different cell types, and signals for cell differentiation, migration, and survival. The basement membrane structure is thought to be set by laminin and collagen IV.

Blastocoel - The fluid-filled cavity in the blastocyst within which the inner cell mass resides.

Blastocyst - A spherical, early-stage embryo containing about 150 cells composed of two sets of cells: An inner cell mass (source of embryonic stem cells) which lies within it and a surrounding outer cell layer called the trophoblast (gives rise to the placenta).

Bone marrow stromal cells - Same as mesenchymal stem cells or MSCs. This heterogeneous population of cells is derived from the non-blood forming fraction of the bone marrow. These stem cells are multipotent, capable of differentiating into bone, cartilage, and fat cells.

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C

3-D cell culture - Encapsulation of cells within a biocompatible natural or synthetic extracellular matrix (as opposed to plating cells on the surface of a petri dish).

CD34+ stem cells - CD34 is a cell surface glycoprotein which acts as a cell-cell attachment factor and is encoded by the CD34 gene. While there are several types of CD34+ cells present in the umbilical cord and bone marrow, CD34+ CD38- are characteristic of pluripotent hematopoietic stem cells.

Cellular therapy - A field of medicine that uses cells to repair tissues that have been damaged by human disease or to generate new tissues with desired functional activities.

Cell line - Cells that can be indefinitely proliferated in culture. They are also described as immortalized.

Cell type - A specialized class of cells characterized by a specific appearance, location, and function. Examples include adipocytes (fat cells), cardiomyocytes (heart muscle cells), chondrocytes (cartilage cells), fibroblasts (connective tissue cells), neurons (nerve cells), and osteoblasts (bone making cells).

Compliance - The inverse of stiffness. Therefore, the more compliant a material, the less stiff it is.

Cord blood stem cells - Same as umbilical cord blood stem cells. These cells are collected from the umbilical cord at birth and can give rise to all the different blood cell types (i.e. hematopoietic).

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D

Differentiation - The process of an undifferentiated stem cell assuming the characteristics of a specialized cell such as an adipocyte or cardiomyocyte over time.

Directed differentiation - Induction of stem cell differentiation into specific cell types (such as a neuron or osteoblast) through changing culture conditions.

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E

Ectoderm (see Germ layers) - The ectoderm is the outermost layer of an embryo. It comes from the inner cell mass (see Inner cell mass) and gives rise to the nervous system, skin, and other outermost specialized tissues and organs.

Embryoid bodies - A mimic of the post-implantation embryonic tissues. They are spheroid groups of cells formed when embryonic stem cells are grown in suspension culture. They contain cells derived from all three germ layers.

Embryonic germ cells - Pluripotent stem cells derived from fetal cadaver germ cells (which give rise to sperm and eggs). They have similar properties to embryonic stem cells.

Embryonic stem cells - Stem cells derived from the inner cell mass of the blastocyst. These stem cells are different from adult stem cells in that not only can they self-renew, they are pluripotent (i.e. can differentiate into any differentiated cell of the developing fetus or organism).

Endoderm (see Germ layers) - The endoderm is the innermost layer of an embryo. It comes from the inner cell mass of the blastocyst (see Blastocyst) and gives rise to inner tissues and organs such as lung and intestines.

Extracellular matrix - The extracellular matrix (ECM) is a mixture of polysaccharides, proteins, and growth factors secreted by cells and surrounds them in tissues. It not only provides the structural support for cells but also contains a variety of biologically active molecules that are highly regulated and critical for determining the action and fate of the cells that it surrounds.

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F

Feeder layer - Feeder cells are typically mouse or human embryonic fibroblasts inactivated by gamma irradiation or mitomycin to prevent cell division. They serve as a basal layer for maintaining stem cells in the undifferentiated state without losing pluripotency. Their purpose is to provide secreted factors, extracellular matrix, and cellular contacts for the maintenance of stem cells.

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G

Germ layers - Three layers present in an early embryo (ectoderm, mesoderm, and endoderm) which eventually give rise to different organs and tissues in the body.

Glycosaminoglycan (GAG) - Long, unbranched polymers of repeating disaccharide units present in the extracellular matrix and fluids of the human body. Each GAG differs from one another by their specific dissacharide unit, the geometry of their glycosidic linkage, the extent of their sulfation, and the core proteins they are covalently bound to.

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H

Hyaluronic acid (Also known as hyaluronan or hyaluronate) - Hyaluronic acid is a unique glycosaminoglycan (GAG) since it is not only unsulfated but also remains unbound to a core protein. It is one of the main components of the extracellular matrix, providing both structural and cell signaling cues. Hyaluronic acid is present in different tissues and fluids with the human body with the highest abundance in the umbilical cord and in synovial fluid.

Hematopoietic - Pertaining to making blood or blood cells. Hematopoietic comes from the Old Greek words haima (blood) and poiesis (to make).

Hematopoietic stem cell (HSC) - A multipotent stem cell capable of differentiating into all other blood cell types. They are found in adult bone marrow, umbilical cord blood, peripheral blood, and in fetal liver.

Hematopoietic cell transplantation - The transplantation of hematopoietic stem cells for blood-forming therapeutic purposes. For example, transplantation of these cells are crucial for reviving a leukemia or lymhoma patient’s ability to make new blood cells after irradiation or chemotherapy.

Heparan sulfate - Heparan sulfate (HS) is a component of the extracellular matrix. It is a highly sulfated glycosaminoglycan that is covalently attached to core proteins to form proteoglycans. Its structure is diverse since during synthesis it undergoes extensive sulfation and epimerization. Heparin is distinct from HS in that it is produced primarily by mast cells (HS is produced by all cells) and is more highly sulfated.

Heterologous - A mixed cell population.

Histocompatible - Refers to tissue or organ transplantation without rejection from the recipient immune system. Histocompatibility usually occurs with transplantation between identical twins.

Human embryonic stem cell (hESC) - Pluripotent stem cell (capable of making all embryonic tissues but not placenta) found in the inner cell mass of the blastocyst (spherical, hollow early embryo).

Hydrogel - A 3-D swollen network of macromolecules typically covalently or ionically linked together. Water is the major component (usually greater than 80%).

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I

In vitro - describes a state or condition that occurs and/or exists outside the body. This term often refers to testing conditions that occur in a laboratory environment.

In vitro angiogenesis tube formation assay - An in vitro angiogenesis model based on endothelial cells such as human umbilical vein endothelial cells (HUVECs) or human microvascular endothelial cells (HMECs) aligning to form a capillary-like tubular networks when cultured on a compatible surface such as Matrigel, Extracel-IVA, collagen, or fibrin.

In vivo - describes a state or condition that occurs and/or exists within the body. This term is often used to describe testing conditions that occur within humans and/or animals.

In vivo angiogenesis plug assay - A biocompatible matrix such as Matrigel or Extracel can be supplemented with angiogenic factors and subsequently injected subcutaneously into a mouse. The injected bolus then forms a plug after gelation in situ. This plug is then removed 1-3 weeks post-injection and examined histologically for newly-formed blood vessels.

Induced pluripotent stem cells - Also known as iPS cells or iPSCs. iPSCs are pluripotent but unlike embryonic cells, they are derived from non-embryonic adult somatic cells which have been engineered to overexpress up to four key proteins which induce their ability to differentiate into a wide variety of cells. A key advantage of iPSCs is their potential to be produced from an individual as a source of autologous cells for future cell therapies. In addition, iPS cells can be used from individuals with specific genetic disorders to prepare rare or inaccessible cells as model systems for drug discovery.

Inner cell mass (ICM) - Small cell cluster attached to the inner surface of the blastocyst which give rise to all embryonic tissues (not included are extra-embryonic tissues such as placenta). These cells are used to make human embryonic stem cell lines.

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L

Lactate dehydrogenase elevating virus (LDEV) - Lactate dehydrogenase-elevating virus (LDEV or LDV) is an enveloped, positive-strand RNA virus of the family Arteriviridae and can infect laboratory mice by implantation with contaminated biological materials (transplantable tumor cell lines or basement membrane extracts derived from Engelbreth-Holm-Swarm (EHS) mouse sarcoma). LDEV infection can adversely affect results from human tumor xenograft studies since the virus alters the host mouse in vivo physiology and can lead to immunological disorders such as hyperimmunoglobulinemia. In some mouse strains, infection can lead to paralysis (Z. Chen et al, J. Virology 1997).

Long-term self-renewal - The ability of stem cells to reproduce in the undifferentiated state over time.

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M

Mammary epithelial cell differentiation - Mammary epithelial cells when grown in three dimensions on certain scaffolds organize themselves into acini (a spheroid with a hollow lumen). The acini are characterized by three layers of cells: luminal, basal epithelial cells, and myoepithelial cells; apicobasal epithelial cell orientation relative to the lumen; basal deposition of its own extracellular matrix; and lactogenesis. MCF-10A is an example of an immortalized mammary epithelial cell line used in vitro to study this process. Since overexpression of oncogenes within MCF-10A disrupts the normal acinal morphogenesis via excessive cell proliferation, these transformed cells provide model systems to understand breast cancer.

Mesenchymal - Refers to the part of the embryonic mesoderm from which bone, cartilage, and connective tissue, as well as circulatory and lymphatic systems in the adult come from.

Mesenchymal stem cell (MSC) - Adult stems cells found in bone marrow which can be differentiated into bone, cartilage, fat, and connective tissues. Also called bone marrow stromal cells.

Mesoderm (see Germ layers) - The mesoderm is the middle germ layer of an embryo. It comes from the inner cell mass of the blastocyst (see Blastocyst) and gives rise to bone, muscle, connective tissues, and the kidneys.

Microenvironment - The collection of insoluble (extracellular matrix, cell-cell interactions, three-dimensional space) and soluble (cytokines, metabolites, dissolved gases) extracellular signals which influence the final differentiated state and function of a cell.

Morphology - The shape and appearance of a cell.

Multipotent -Refers to stem cells which can differentiate only into a subset of all adult tissues. Adult stem cells are typically multipotent. For example, hematopoietic and mesenchymal stem cells can only differentiate into blood and mesoderm-derived cell types, respectively (See Pluripotent and Totipotent).

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N

Neural stem cell - An adult stem cell that can differentiate into new nerve cells (neurons) and their supporting cells (glia (such as astrocytes) and oligodendrocytes).

Neurons - These nerve cells are composed of a cell body and processes (axon and dendrites). Neurons transmit impulses to other cells by neurotransmitter release at synapses.

Neurospheres - Free-floating, spherical aggregates of neural stem cells which can proliferate in culture and can differentiate into neurons and glia.

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O

Oligodendrocyte - A neuron-supporting cell (one type of glial cell) which insulates the neuron by forming a myelin sheath around the neural axon.

Oligopotent progenitor cells - Progenitor cells that cannot self renew but can give rise to a small subset of differentiated cells.

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P

Passage - Passaging cells is the process of maintaining a cell line by diluting them in fresh medium.

Plasticity - The concept that stem cells can change the range of cell lineages they can differentiate into in response to environmental signals.

Pluripotent - Pluripotency characterizes human embryonic stem cells. This quality allows differentiation into any cell of the developing fetus and adult organism with the exception of cells that become the placenta (the cells surrounding the blastocyst’s inner cell mass (the trophoblast) are responsible for generating the placenta).

Polar body - Small cells produced when an egg cell undergoes meiosis. These cells eventually degenerate.

Potency - Refers to the flexibility of a stem or progenitor cell to form cells of different lineages. Unipotent cells can only form a single cell lineage; oligopotent cells can form two or more (but not all) lineages within a specific tissue (e.g. neural stem cells); multipotent cells can form all the different lineages present in a specific tissue (e.g. hematopoietic stem cells); pluripotent cells can form all cell lineages except extraembryonic cell types (e.g. human embryonic stem cells); totipotent cells can form any cell lineage in the organism (e.g. zygote).

Post-implantation embryo - Embryos of ages between and including the stages of implantation and placentation.

Pre-implantation embryos - Embryos of all ages up to and including the stage of the blastocyst.

Progenitor cell - An early descendent of a stem cell which can no longer self-renew and has less potency than its parent stem cell (i.e. it can differentiate into fewer cell types).

Proliferation - The expansion of a population of cells by mitosis.

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R

Regenerative medicine (See Cellular therapy) - The field of medicine that uses specific stem-cell derived differentiated cells to repair damaged tissue in humans.

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S

Somatic stem cells - The same as adult stem cells (see Adult stem cells).

Somatic cells - All cells in an organism except egg and sperm cells.

Somatic cell nuclear transfer - The nucleus of a somatic cell is transferred to an egg whose nucleus has been removed. The result is an embryo with identical genetic makeup as the original somatic cell. Such transfer can be used in theory to generate human embryonic stem cell lines which will not be rejected by the adult somatic cell donor during cell therapy.

Stem cells - Undifferentiated cells with two abilities: 1) the ability to self-renew (i.e. one stem cell can divide and make more stem cells) 2) and the ability to differentiate into specialized cells.

Stromal cells - Stroma comes from the Greek word “bed”. Loose connective tissue cells whose role is to provide a matrix for cells performing the function of the specific organ. They are found in the uterine mucosa, ovary, and hematopoietic system. Stromal cells are a critical component of bone marrow matrix.

Surface markers - Cell-type specific proteins that reside on the cell surface. These proteins can be detected and hence identification of cells can be performed using corresponding antibodies.

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T

Teratoma - A benign tumor which contains cells derived from all three germ layers. Teratoma formation after xeno-transplantation of human embryonic stem cells into immunocompromised mice confirms the stem cells’ pluripotency.

Totipotent - describes the ability of a stem cell to become any embryonic or extraembryonic tissue (see Potency).

Transdifferentiation - Differentiation of stem cells from a particular tissue into cells of a different tissue (see Plasticity).

Transplantation biology - The study of transplantation of cells, tissues, and organs.

Trophectoderm - see Trophoblast.

Trophoblast - Extraembryonic cells which become the placenta. The trophoblast, together with the inner cell mass, comprise the blastocyst. The trophoblast represents the outer spherical surface of the blastocyst within which the inner cell mass resides; the remainder of the blastocyst interior is a fluid filled space called the blastocoel.

Tumor xenograft - The tumor cells of one species which are transplanted into another species. In preclinical drug development, human cancer cells or a tumor biopsy derived from a particular human tissue is implanted either subcutaneously or orthotopically in an immunodeficient mouse. Tumor growth and take rate are usually enhanced by mixing the cells with a commercially available extracellular matrix such as Matrigel or Extracel-X before implantation. The end result is an in vivo human tumor model (also known as a xenograft model).

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U

Umbilical cord blood stem cells - Hematopoietic stem cells collected from the umbilical cord at birth.

Undifferentiated - Describes cells whose specialized structure(s) and function(s) remained undetermined.

Unipotent stem cells - Stem cells which can still self-renew but can only differentiate into one specialized cell type. An example is skin stem cells.

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