BIOT 412, Stem Cells, Ch. 12 December, 2012

Stem cells -Ability to renew themselves -Differentiate into diverse range of specialized cell

History The term "stem cell" was proposed for scientific use by the Russian histologist Alexander Maksimov (1874–1928) at Congress of Hematologic Society in Berlin in It postulated existence of haematopoietic stem cells.

Definitions Related to Stem Cells Differentiation Qualitative change in cellular phenotype resulting from the onset of synthesis of new genetic products. Differentiation is commonly identified by production of novel protein Maturation Qualitative change in the cellular phenotype or the cellular constituent proteins leading to functional competence Self Maintenance The ability to maintain its own number without input from other cell stages is self maintenance Self-Renewal This term applies “to make like new cells” or simple rejuvenation

Self-Replication -Duplication -Production of identical cell Regeneration: “to make something again” that was already preexisting. It could apply to tissue or population of cells that contain ability to self maintain and regulation.

Types of Stem Cells Three broad categories, based on their ability to differentiate. Totipotent stem cells are found only in early embryos. Each cell can form a complete organism (e.g., identical twins) Pluripotent stem cells exist in the undifferentiated inner cell mass of the blastocyst and can form any > 200 different cell types in body Multipotent stem cells are derived from fetal tissue, cord blood and adult stem cells; they can form a limited number of cell types

Sources of stem cells Embryonic stem cells - are harvested from the inner cell mass of the blastocyst seven to ten days after fertilization RELAYES TO TRANSGENICS Fetal stem cells - are taken from the germline tissues that will make up the gonads of aborted fetuses Umbilical cord stem cells - Umbilical cord blood contains stem cells similar to those found in bone marrow Placenta derived stem cells - up to ten times as many stem cells can be harvested from a placenta as from cord blood Adult stem cells - Many adult tissues contain stem cells that can be isolated

Totipotent When given  the right differentiation factors

Pluripotent stem cells

Embryonic Stem Cells(ESC) Martin Evans & Matthew Kaufman, -First derived ESC from mouse embryo in Most human embryonic stem cells come from embryos developed from eggs fertilized in vitro for research purposes with informed consent of the donors -They are not derived from eggs fertilized in a woman's body -The embryos from which human embryonic stem cells are derived are typically four or five days old and are a hollow microscopic ball of cells called the blastocyst -The blastocyst includes three structures: the trophoblast, which is the layer of cells that surrounds the blastocoel, a hollow cavity inside the blastocyst; and the inner cell mass, which is a group of cells at one end of the blastocoel that develop into the embryo proper. -Embryonic Stem (ES) cells are pluripotent. This means they are able to differentiate into more than 220 cell types in the adults.

Adult Stem Cells - Partially differentiated cells; multipotent - Found throughout the body after embryonic development; multiply by cell division to replenish dying cells and regenerate damaged tissues - Also known as somatic stem cells; they can be found in juvenile as well as adult animals and humans -Scientific interest is their ability to divide or self-renew indefinitely, and generate all the cell types of the organ from which they originate

Multipotent stem cells

Hematopoietic stem cells (HSCs) - They are multipotent stem cells that give rise to all the blood cell types including myeloid (monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes/platelets, dendritic cells), and lymphoid lineages (T-cells, B-cells, NK-cells) - HSCs are found in the bone marrow of adults, which includes femurs, hip, ribs, sternum, and other bones. - Cells can be obtained directly by removal from the hip using a needle and syringe, or from the blood following pre-treatment

Stem Cell lines - Stem cell line is a population of cells that can replicate themselves for long periods of time in vitro, meaning outside of the body, provided the environment is like that found in the mammalian body - There different types of stem cell lines - These cell lines are useful in human developmental biology, drug discovery, and transplantation medicine

Embryonic stem cell lines Are created from embryos. A living single stem cell from the embryo is placed in a Petri dish (without agar) and provided with nutrients and growth factors that simulate those found in the womb. The resulting cell line will continue to divide provided it receives sufficient chemical signals signaling it to remain undifferentiated. - The U.S. National Institutes of Health currently lists only 21 lines, out of sixty, that are available for distribution to researchers. THEY ARE NOT VERY USEFUL.

Adult Stem Cell Lines Adult stem cell lines isolated from mature tissues, as are cells isolated from umbilical cord blood. However, these cells have a genetic imprint of the host they were taken from, thus limiting their therapeutic use in genetic disorders. Also, adult stem cells are not totipotent or pluripotent like embryonic stem cells, but rather more specialized cells that are multipotent

Induced pluripotent stem cells They are commonly abbreviated as iPS cells or iPSCs, are a type of pluripotent stem cell artificially derived from a non-pluripotent cell, typically an adult somatic cell, by inducing a "forced" expression of certain genes.

Human Relevance and Role of Stem Cells -Treatments offered by stem cell in heart diseases, diabetes, cancer, and diseases of the nervous system, such as Parkinson’s disease and Alzheimer’s disease. -Stem cell therapies: Bone marrow transplants (BMT) are a well known clinical application of stem cell transplantation. The isolation of additional stem and progenitors cells is now being developed for many other clinical applications.

Skin Replacement Neural Stem Cells for Brain & Spinal Cord Repair Spinal Cord Injury Parkinson’s disease Stem Cell Transplant for Cancer and other Diseases Replace dysfunctional bone marrow