Stem Cells

Stem cells are generally rare cells with the ability to differentiate into mature cells of one or more lineages whilst also containing the unique potential for self-renewal. There is significant therapeutic potential for the regeneration of damaged tissues such as bone marrow, neurones or skin within the ability of endogenous or transplanted stem cells. This unit will cover the basic properties of stem cells and explain the underlying control mechanisms of self renewal, specific commitment and repair. Recent discoveries on the common pathways in cancer cells and stem cells will be used to illustrate the current research on their close association. Topics covered will include, ’Control of ES and IPS cell differentiation’, ’Cancer stem cells’, and ‘Clinical applications of stem cells’.

BIOL31751 Pre-requisite is BIOL21172

Stem cells are generally rare cells with unique potential for self-renewal and which form progenitors that can differentiate into mature cells of one or more lineages. The ability of endogenous or transplanted stem cells to repair tissues has significant therapeutic potential for the regeneration of damaged tissues such as bone marrow, skin, pancreas, neurons and many others. The aim of this unit is to describe the properties of stem cells and to explain the mechanisms underlying the control of self-renewal, specific lineage commitment and repair. Recent reports on common-pathways in cancer cells and stem cells will be used to illustrate the current thinking on the close association between stem cells and cancer.

Students should have acquired a detailed understanding of the features of both embryonic, embryonic-like and adult stem cells, how their activity is assayed, the pathways involved in the intrinsic and extrinsic (environmental) control of their phenotype and the association between stem cells and cancer. As stem cell biology is a rapidly progressing field, any current "hot" areas in stem cell biology will also be covered.

Topics to be covered will include: 

• Introduction to the field including definitions of what stem cells are and what they are not; definitions of potency and other key terms; brief history of the field; overview of different stem cell types (embryonic, fetal, adult/tissue and cancer); stem cell properties and examples of how they are investigated. 

• Embryonic Stem (ES) cells; both mouse and human ES cells will be discussed and their similarities and differences compared. The characteristics and properties of ES cells: pluripotency and self renewal will be discussed as well as how to test for these; molecular mechanisms regulating pluripotency and maintenance of the stem state. 

• Induced Pluripotent Stem (IPS) Cells: original generation by Yamanaka and newer methods by which they can now be generated; their properties and similarities and differences from ES cells; issues and problems in their generation and maintenance; methods to bi-pass the pluripotent state and generate progenitors; potential for use for disease modelling toxicology/drug testing and cell therapy. 

• Control of ES and IPS cell differentiation: embryoid body formation and how this technique has been adapted to channel stem cells into single lineages/differentiated cell types; challenges in recapitulating development and developing defined conditions to induce ES and IPS cells to develop along a prescribed line of development to a desired differentiated cell type (examples from pancreatic beta cells, cardiomyocytes, neural lineages and chondrocytes). 

• Mesenchymal Stem Cells: their discovery and early analysis; tissue localisation; potential for tissue repair (local recruitment, differentiation; anti-inflammatory effects; immunosuppressive properties); latest strategies for isolation/cell surface markers/characterisation; applications in tissue regeneration (e.g. cartilage and bone). 

• Haematopoietic stem cells: description of the haematopoietic system and the properties of its components, including the concept of the HSC niche; the markers and techniques used to isolate HSCs and the in vitro and vivo assays used to assess them; the ontogeny of HSCs, their regulation, and their therapeutic use in human disease. 

• Tissue-specific stem cells: skin as an example: structure and development; experimental evidence for different types of stem cells that contribute to skin homeostasis, the effects of injury and disease on skin stem cells, and potential therapeutic applications. 

• Clinical applications of stem cells: What is needed for cell therapy? How far have we gotten and what are the problems? Discussion of some of the most advanced ES generated phase 1 clinical trials (e.g. ACT and London Eye project: retinal pigmented epithelium). Reference to established HSC and prototype MSC therapies. 

• Cancer stem cells: controversy and identification of cancer stem cells; impact on anti-cancer therapies; methods to control cancer stem cells. 

• Endogenous regulation of stem cells: knowledge gained from model organisms, Drosophila as an example; niche maintenance and age-related changes to stem cells.

Written exam - 2 hour written examination consisting of 5 questions for which the student selects 1 to answer in essay format (60%).

Online MCQ assessments throughout the unit (15%).

Coursework essay (25%).
 

Coursework essay and MCQ Quizzes.
 

Reading material will be current reviews and primary papers