UNSW Embryology

Stem Cells - Neural

© Dr Mark Hill (2009)

Acknowledgements

Introduction

The term "stem cell" is now used widely to cover many different cells derived from both embryo and adult tissues.

A useful guide (online PDF document) to stem cells was produced in a report by the National Institute of Health (NIH, USA, May 2000) Stem Cells: A Primer (note large size - 4.84 Mb) and more recently NIH has established a Stem Cell information page.

Page Links: Introduction | Some Recent Findings | GENM0202 | Diseases | Adult Neurogenesis | References | WWW Links | Glossary | Terms

Some Recent Findings

Lee MW, Moon YJ, Yang MS, Kim SK, Jang IK, Eom YW, Park JS, Kim HC, Song KY, Park SC, Lim HS, Kim YJ. Neural differentiation of novel multipotent progenitor cells from cryopreserved human umbilical cord blood. Biochem Biophys Res Commun. 2007 Jun 29;358(2):637-43.

Corti S, Nizzardo M, Nardini M, Donadoni C, Locatelli F, Papadimitriou D, Salani S, Del Bo R, Ghezzi S, Strazzer S, Bresolin N, Comi GP. Isolation and characterization of murine neural stem/progenitor cells based on Prominin-1 expression. Exp Neurol. 2007 Jun;205(2):547-62.

Diseases

The following list are potential neural disease that stem cells may have future therapeutic benefits:

central nervous system malignancies

Amyotrophic lateral sclerosois (ALS)

Hirschsprung's disease (agangliosis)

Parkinson's disease

Retinal repair

Spinal cord repair

Stroke

Adult Neurogenesis

Adult neurogenesis is seen mainly in two neurogenic centers: subventricular zone (adjacent to lateral ventricles) and subgranular zone (dentate gyrus of the hippocampus).

Subventricular Zone (SVZ)

The subventricular zone (SVZ) neural stem cell niche appears to asociate closely with a planar vascular plexus. Furthormore it has been shown that these cells also form unique contacts with the vasculature which lack astrocyte endfeet and pericyte coverage.

GENM0202

This lecture is an introduction to stem cells and their use in Neuroscience. The key components covered are: historic background, stem cells, blastocyst, pluripotential, developmental stem cells, adult stem cells, therapeutic applications.

The lecture slides contain enough information as an introduction to the subject for this level of study. If you are interested in further reading, I have also included below links to more detailed textbooks with further information and images. Please note this additional information is not necessarily examinable, but may be useful if you have not previously studied biology. The link below to lecture slides allows you to open and view the slides in your web browser or download the PDF document for later viewing/printing. The online text Developmental Biology links listed below are worth reviewing for this lecture.

Link to lecture slides allows you to open and view the slides in your web browser or download the PDF document for later viewing/printing. 1 slide/page viewing 48 pages | 3 slide/page printing 12 pages | 6 slide/page printing 8 pages.

References

Links: Reviews | Articles | Online Textbooks | Search Textbooks | Search PubMed | Glossary

Reviews

Yamashima T, Tonchev AB, Yukie M. Adult hippocampal neurogenesis in rodents and primates: endogenous, enhanced, and engrafted. Rev Neurosci. 2007;18(1):67-82.

Kim SU. Genetically engineered human neural stem cells for brain repair in neurological diseases. Brain Dev. 2007 May;29(4):193-201.

Kornblum HI. Introduction to neural stem cells. Stroke. 2007 Feb;38(2 Suppl):810-6.

Belegu V, Oudega M, Gary DS, McDonald JW. Restoring function after spinal cord injury: promoting spontaneous regeneration with stem cells and activity-based therapies. Neurosurg Clin N Am. 2007 Jan;18(1):143-68, xi.

Articles

Corti S, Nizzardo M, Nardini M, Donadoni C, Locatelli F, Papadimitriou D, Salani S, Del Bo R, Ghezzi S, Strazzer S, Bresolin N, Comi GP. Isolation and characterization of murine neural stem/progenitor cells based on Prominin-1 expression. Exp Neurol. 2007 Jun;205(2):547-62.

Lee MW, Moon YJ, Yang MS, Kim SK, Jang IK, Eom YW, Park JS, Kim HC, Song KY, Park SC, Lim HS, Kim YJ. Neural differentiation of novel multipotent progenitor cells from cryopreserved human umbilical cord blood. Biochem Biophys Res Commun. 2007 Jun 29;358(2):637-43.

Heanue TA, Pachnis V. Enteric nervous system development and Hirschsprung's disease: advances in genetic and stem cell studies. Nat Rev Neurosci. 2007 Jun;8(6):466-79.

Guillemot F. Cell fate specification in the mammalian telencephalon. Prog Neurobiol. 2007 Mar 7

Ross JJ, Verfaillie CM. Evaluation of neural plasticity in adult stem cells. Philos Trans R Soc Lond B Biol Sci. 2007 Feb 5;

Prentice DA, Tarne G. Treating diseases with adult stem cells. Science. 2007 Jan 19;315(5810):328.

Search PubMed: May 2007 "neural stem cells" 5,427 reference articles of which 963 were reviews.

Search PubMed Now: neural stem cells

WWW Links

International Society for Stem Cell Research (ISSCR) is an independent, nonprofit organization formed in 2002 to foster the exchange of information on stem cell research.

(USA) NIH - Stem Cell Information: NIH Stem Cell Basics NIH Stem Cell Information | NIH Stem Cell Reports :

Regenerative Medicine 2006 PDF: Chapter 3: Repairing the Nervous System with Stem Cells (372 KB PDF)

Stem Cells: Scientific Progress and Future Research Directions (2001)

National Human Genome Research Institute Cloning/Embryonic Stem Cells

University of Michigan Stem Cells Explained

Glossary of Terms

A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z

Terms

Alzheimer's Disease - (AD) A neurodegenerative disease associated mainly with ageing and the most common form of dementia. Involves neurons in the parts of the brain that control thought, memory and language. Histopathology is shown postmortem by extracellular beta-amyloid (Aß) fibrils plus intraneuronal tau (a microtubule associated protein) filaments. Named after Aloysius Alzheimer (1864-1915), a German psychiatrist and neuropathologist first published case of "presenile dementia". (More? Neural Notes | Medline Plus - Alzheimer's Disease)

Amyotrophic Lateral Sclerosis - (ALS, Lou Gehrig's disease) A postnatal neurological disease of the central nervous system, affecting the spinal cord motor neurons and brain. Henry Louis "Lou" Gehrig (1903–1941), was an American baseball player in the 1920s and 1930s who suffered from this disease. (More? Neural Notes | Medline Plus - Amyotrophic Lateral Sclerosis)

blastocyst - (Greek, blastos = sprout + cystos = cavity) The early stage in embryo development, in humans week 1 and 2, before implantation. The blastocyst consists of cells forming an outer trophoblast layer, an inner cell mass and a fluid-filled cavity. The blastocyst inner cell mass is the source of true embryonic stem cells capable of forming all cell types within the embryo. (More? Week 1 - Blastocyst | Week 2 Notes | Stem Cell Notes)

bone marrow - The cellular components found within the core of bones, mainly long bones, which contain the adult blood stem cell population and a range of other cell types. (More? Musculoskeletal Development - Bone | Musculoskeletal Development)

bone marrow stromal cells - (BMSCs) These are pluripotental cells from bone marrow that can potentially differentiate into a range of connective tissue and muscle cell types (cardiomyocytes, rhabdomyocytes, hepatocytes, osteocytes, chondrocytes, tencoytes, adipocytes, smooth muscle cells). These cells have therefore been seen as a source of stem cells for tissue repair. (More? Musculoskeletal Development - Bone | Musculoskeletal Development)

chimera - (Greek, pronounced ky-MIR-uhs) A mythical monster with the head of a lion, the body of a goat, and the tail of a serpent. Today used to describe a mixing of biological molecules either: 1. animals that have been genetically engineered 2. development studies where different species cells have been mixed, example chick-quail chimera, (More? Neural Crest Notes) 3. Modified proteins containing parts of 2 different proteins.

cord blood - A term used to describe blood collected from the placenta usually after birth. Has been identified as a source of stem cells with potential therapeutic uses and is stored in Cord Blood Banks throughout the world. (More? Placenta Development | Stem Cell)

enteric nervous system

ES cell - An Embryonic Stem cell derived from the inner cell mass of the blastocyst, which is totipotential and can be grown undifferentiated in tissue culture (in vitro). (More? Stem Cell Notes)

glial cell - A cell within the nervous system that does not itself transmit electrical and chemical signals, but which provides metabolic and structural support for neurons. (More? Neural Notes)

hippocampal neurogenesis

“knock out” mice - A term used to describe the molecular biology technique of introducing a germ line gene specific disruption that results in mice that do not produce the protein product of that gene, it has been "knocked out". Technique required the development of stem cells to carry out the manipulation. (More? Stem Cell Notes | Molecular Notes | Mouse Notes)

medulloblast - An undifferentiated cell of the embryonic neural tube that can develop into either a neuroblast or spongioblast similar to a neural stem cell. A medulloblastoma is a tumor that has been suggested to form from transformed neural stem cells.

medulloblastoma - A tumor that has been suggested to form from transformed neural stem cells.

neural crest - cell region at edge of neural plate, then atop the neural folds, that remains outside and initially dorsal to the neural tube when it forms. These paired dorsal lateral streaks of cells migrate throughout the embryo and can differentiate into many different cell types (= pluripotential). Those that remain on the dorsal neural tube form the sensory spinal ganglia (DRG). Neural crest cells also migrate into the somites. (More? Neural Crest Notes)

neural stem cell (NSC) Stem cells within the central nervous system (CNS) that proliferate indefinitely and give rise to either neurons, astrocytes, and oligodendrocytes.

neural stem cell niche - Locations within the nervous system that multipotent stem cells reside and participate in specialized microenvironments that support self-renewal and differentiation.

neural tube - The third stage in early development of the central nervous system. In the trilaminar embryo (ectoderm, mesoderm, endoderm) the central region of the ectoderm (in the midline above the mesodermal notochord) initially forms a columnar epithelium described as the neural plate. This epithelium will fold dorsally to form the neural groove, which then fuses to form an initially open at either end hollow neural tube. The neural tube forms the central nervous system (brain and spinal cord). Developmental sequence: neural plate -> neural groove -> neural tube -> Central Nervous System -> brain and spinal cord. (More? Neural Notes)

neurogenesis - the process of formation of the neural system. This begins with segregation of the neural plate from the ectoderm of the trilaminar embryo by folding to form initially the neural groove, which then fuses to form the neural tube (the central nervous system progenitor, brain and spinal cord) and associated neural crest. (More? Neural Notes)

neuron - (neurone) The cell forming the unit basis of the nervous system (both central and peripheral) capable of generating an action potential and releasing neurotransmitter. There are many different types of neuronal cells. (More? Neural Notes)

olfactory epithelium - The specialised sensory epithelium that lines the nasal cavity associated with smell. Some cells within the adult epithelium remain as stem cells which can be isolated and purified. (More? Senses Smell | Senses Notes | Stem Cell Notes)

Parkinson's disease - (paralysis agitans, shaking palsy) A postnatal neurological disease of the central nervous system, typically in ageing and more common in men than in women. The neurons affected are those in the brain that control muscle movement and have dopamine as their neurotransmitter. Named after James Parkinson (1730-1813), an English physician who made the detailed description of the disease in "An Essay on the Shaking Palsy" (1817) (More? Medline Plus - Parkinson's Disease) | Pearce JM. Aspects of the history of Parkinson's disease. J Neurol Neurosurg Psychiatry. 1989 Jun;Suppl:6-10)

pluripotent A stem cell term describing the ability of a stem cell to form (differentiate) into many different cell types. The term totipotent means that the stem cell can form all embryo cell types. (More? Stem Cell Notes)

spinal cord - The caudal end of neural tube that, together with the brain (rostral end of neural tube), forms the central nervous system (CNS). Note: the process of secondary neuralation contributes the very caudal end of the spinal cord. (More? Neural Notes)

Stage-Specific Embryonic Antigen-1 - (SSEA-1) A cell surface embryonic marker (antigen) which has a role in cell adhesion, migration and differentiation and is often differentially expressed during stem cell development. Can be identified by Davor Solter monoclonal antibody MC-480 (SSEA-1). (More? Stem Cell Notes)

Stage-Specific Embryonic Antigen 4 - (SSEA-4) A cell surface embryonic marker (antigen) of human teratocarcinoma stem cells (EC), human embryonic germ cells (EG) and human embryonic stem cells (ES) which is down-regulated following differentiation of human EC cells. This antigen is not expressed on undifferentiated murine EC, ES and EG cells but upregulated on differentiation of murine EC and ES cells. Can be identified by Davor Solter monoclonal antibody MC-813-70 (SSEA-4). (More? Stem Cell Notes)

stem cell - Term used to describe a cell with the potential to reproduce itself indefinitely, as well as differentiate into any other embryo tissue cell types. There are also a number of different specialised stem cell definitions: totipotential stem cell (as described above), pluripotential stem cell (capable of forming a number of different cell types), embryonic stem cell (derived from the blastocyst), cord blood stem cell (derived from placental cord blood), and adult stem cell (derived from adult or postnatal tissue). (More? Stem Cell Notes)

Stem Cell Antigen 1 - (Sca-1) A cell surface marker (antigen) for mouse hematopoietic progenitor/stem cell subset. It is a member of the Ly-6 family of GPI-linked surface proteins (Mr 18 kDa). (More? Stem Cell Notes)

totipotent - Term that describes the ability of a cell (stem cell) to form an entire organism or any tissue from that organism. Totipotential suggests a wider differentiation ability than pluripotential, where there is a restriction to a particular group of cell types such as that seen for bone marrow blood stem cells. (More? Stem Cell Notes)

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