This interim note should be read in conjunction with the Somatic Cell Nuclear Transfer (SCNT) chart. Click here to see this chart
(This summary has been ‘fast tracked’ due to (1) public interest in this rapidly developing field from both a biological and ethical point of view and, (2) the fact that ‘stem cells’ and terms such as ‘pluripotency’ are beginning to be included in ‘A’ level Biology in schools in England (UK), A more detailed essay will appear in due course. A CELLpics chart illustrating induced Pluripotent Stem Cells (iPS cells) is in current development.)
Regenerative Biology and Stem Cell Biology in Context
- ‘Stem cell biology’ is currently a very ‘hot topic’ but it is really neither a separate discipline, nor a concept. It is a fast developing technology involved with the targeting, isolation, possible modification, and often culturing, of a very important type of cell.
- Stem cell biology is a part of ‘regenerative biology’. Regenerative biology embraces regeneration in plants and animals. A striking example of regeneration in animals may be seen in starfish and planaria. Where the idea or concept of regenerative biology is applied to humans it is called regenerative medicine. When plants produce daughter plants by vegetative propagation e.g. strawberry runners, or when cuttings are taken and grown, the term ‘cloning’ is used. ‘Cloning’, when used in relation to stem cell work in mammals is used in a specialist and defined way.
- There are two main driving forces behind stem cell biology as applied to humans.
- The first is the desire to be able to replace damaged or diseased tissue/organs without recourse to organ donation. (There are not enough suitable organs from donations to satisfy the demand, and all transplants carry some risk of rejection. Organ recipients may also be affected by taking the required immunosuppressive drugs).
- The second driving force is the need to be able to culture specific human stem cells to (1) study normal and disease development at the level of the cell, and (2) use stem cells for medicinal drug discovery and testing.
Key Points in Stem Cell Biology
What is a stem cell and why are some types more important than others?
- There are two main types of stem cell: (1) embryonic stem cells (ES cells), sometimes referred to as plain ‘stem cells’ and, (2) adult stem cells, sometimes referred to as somatic stem cells.
- (1) An embryonic stem cell (ES cell) is a cell that can continue to divide indefinitely to produce unaltered daughter cells that can also continue to divide, more or less, indefinitely (given the appropriate conditions). Some of these daughter cells can specialise or differentiate to carry out a specific task. Embryonic stem cells are found in the inner cell mass of the blastocyst (see CELLpics chart).
- (2) Adult stem cells, also called somatic stem cells, are found in various parts of the body (see below) and contribute to the supply of new replacement cells for that tissue. They are found in adult tissue such as skin and divide asymmetrically. This means each adult stem cell divides to produce one daughter stem cell and one daughter cell that will differentiate to carry out a specialised task.
- Biologists describe stem cells according to their potential or potency.
- Totipotent cells can give rise to ALL cell types that make up the organism concerned. The term is mainly used of plant cells. Totipotent stem cells are found in plant meristems but their presence in vertebrate cells is considered to occur only at the 2-cell stage after egg fertilization.
- Pluripotent stem cells can give rise to most, but not all, of the various cell types required to make up a body, including germ cells. Embryonic stems cells (ES cells) are pluripotent.
- Multipotent single stem cells can give rise to the multiple of cell types that constitute an entire tissue but only with that tissue group e.g. haematopoietic (blood forming) stem cells will only form all the various types of blood cells. Adult stem cells are multipotent.
- The most useful stem cells are those that are the least specialised and have the greatest potential or potency. Mutipotent and pluripotent stem cells are the types generally used in animal and human stem cell biology.
- Multipotent stem cells are found in various parts of the body including bone marrow, skin, liver, intestinal villi, pancreas, lungs and reproductive organs where they contribute to the supply of new cells. Adult stem cells taken from blood in the umbilical cord have been used at Newcastle University (UK) to grow liver tissue. Some cancer cells also have their own stem cells. Stem cells of this type are very important physiologically and therapeutically and are used in, for example, bone marrow transplants; unfortunately the number of adult stem cells available is not high.
- Pluripotent stem cells. These stem cells represent the ‘gold standard’ in terms of potency in stem cell biology. Quite simply they are as near as one can get to the ‘universal base line cell’ in animals because they can differentiate into almost any type of cell, (except ‘extra-embryonic’ tissues such as amnion, chorion and other components of placenta – but this is in dispute). Induced or reprogrammed stem (iPS) cells come into this category.
- induced Pluripotent Stem (iPS) Cells
(A CELLpics chart illustrating iPS cells is currently under development)
The derivation of embryonic stem cells from donated human eggs is destined to create ethical issues for the foreseeable future although most of the eggs available are classed as ‘spare’ or ‘left over’ from in vitro fertilization (IVF) treatments. The production and extraction of eggs is in no way a simple procedure. Pre-treatment with hormones is required and the physical extraction of eggs is not without potential difficulties and discomfort. For these and other reasons stem cell biologists have pursued other methods of obtaining “embryonic stem cell like” cells from more plentiful sources and using more ethically acceptable procedures.
- Research has shown that, rather amazingly, ordinary skin cells can be treated to induce them to function in an embryonic stem cell like way.
- These cells are called induced Pluripotent Stem (iPS) Cells and cells produced by this technique are said to have been ‘reprogrammed or re-engineered’, ‘de-differentiated’, ‘wound back,’ ‘reset’ or, by the media, ‘rebooted’.
- ‘Reprogrammed’ perhaps best describes the treatment.
- de-differentiated’ well describes the re-establishment of the pluripotent state and the ‘turning off’ of the system that causes a cell to differentiate; to become a specialist cell.
- The technique of producing stem cells by induction is developing rapidly and the prospects are encouraging. There are however critics who say that the ‘i’ in ‘iPS cells’ should stand for ‘incomplete’ pluripotent stem cells and that only time and research will show whether they provide a ‘silver standard’ in stem cell work.
- Basically the skin cell is reprogrammed by having three or four selected genes introduced into its nucleus. This can be done using retroviruses, but more recently the safer adenoviruses have been used. Once inserted into the nucleus the specialist genes produce chemical gene products. The gene products then change the cell into one that is pluripotent and has “stem cell like properties”.
- Human Induced pluripotent cells are finding a major use in the fields of drug discovery and testing. Here they can sometimes provide more useful information than similar tests done on animals. They are also very useful for studying disease and disorders at a developing cell level.
The latest, as at August 2008
- Research reported in August 2008 shows a new major proof of principle. Scientists working at the Harvard Stem Cell Institute (Harvard University, USA) have been able, in living mice, to convert adult pancreatic cells into insulin producing beta cells. They brought about this altered functioning in adult pancreatic cells by using viruses to ferry just three selected genes into the cells.
- The Harvard team altered pancreatic cell function without using either iPS cells or embryonic stem cells.
- The process is called ‘cell switching’ or ‘lineage switching’ and is a landmark in regenerative medicine but has yet to be shown that it can work in other cell systems.
Future perfect? The next phase
- More research will have to be done on cell switching with the aim of altering the function of cells by chemicals or other drugs. Although something of a landmark, cell switching is at the ‘proof of principle’ stage and its possible therapeutic use is a long way off.
- iPS cells will continue to be very important for studying disease and disorder development from cell level upwards; also for drug development and testing. iPS cells will be invaluable for growing replacement tissues and organs for transplant use.
- Human embryonic stem cells (hESCs) are likely to remain the ‘gold standard’ against which other stem cells and techniques are measured. hESCs have a high quality, viability and efficiency rating.
Challenge your Critical Thinking
- Fast forward to about the year 2070. You are a Forensic Scientist or Pathologist and you are given two human tissue samples from the same person. One is heart muscle tissue from the left ventricle, the other is skin cells. You carry out a DNA analysis of the nuclear and mitochondrial DNA and find a mismatch between the mitochondrial DNA from the two samples. The nuclear DNA from the two samples matches. Assuming the samples have not been contaminated, suggest what you might put in your report as a possible reason for the mismatch. [Clue: in 2070 you remember an old text book mentioning something called SCNT]
- Regenerative medicine and stem cell science are at a very exciting phase and there is much ‘hype’ in the media about what they may be able to do for people with disorders such as Parkinson’s disease. Clinics in some parts of the world are even offering, at considerable cost, stem cell treatments and ‘cures’. At the time of writing (November 2008) no treatments using a stem cell therapy have beensubjected to the rigours of the complete clinical trials procedure used in the Western World. There are therefore NO properly tested acceptable stem cell cures available at present.
Links to websites. There are many websites containing information about regenerative biology and stem cells. The following three have been specially selected. The first two have many notes and a useful glossary; the third has an interesting short video clip.
http://www.isscr.org [At home page click on ‘public’ for ‘basics’ and ‘beyond basics’]
http://www.eurostemcell.org [At home page click on ‘Stem cells’ for FAQs and Glossary]
http://www.nyscf.org [At the home page click on ‘watch NYSCF videos’ and select ‘Stem Cells: Developing New Cures]