Chapter 6: Cell divisions

6.1 The cell cycle

6.2 Mitosis

6.3 Meiosis

6.4 The organisation and specialisation of cells

6.5 Stem cells

Stem cells All cells in plants and animals begin as undifferentiated cells and originate from mitosis or meiosis. They are not adapted to any particular function (they are unspecialised) and they have the potential to differentiate to become any one of the range of specialised cell types in the organism. These undifferentiated cells arc called stem cells. Stem cells have a special ability to divide and renew themselves for extended periods of time. Cells such as muscle or nerve don't normally replicate, but stem cells will repeatedly proliferate. Stem cells are able to undergo cell division again and again, and are the source of new cells necessary for growth, development, and tissue repair. Once stern cells have become specialised they lose the ability to divide, entering the G phase of the cell cycle. The activity of stem cells has to be strictly controlled. If they do not divide fast enough then tissues are not efficiently replaced. leading to ageing. However, if there is uncontrolled division then they form masses of cells called tumours, which can lead to the development of cancer. Stem cells also have therapeutic potential for creating tissues. The waiting lists for organ donation are overwhelming and many people die whilst waiting for an organ transplant. Certain types of stem cells may also provide a source of cells to treat a broad range of conditions such as Parkinson's disease, burns, diabetes and cardiovascular diseases. http://www.explorestemcells.co.uk/ is a great resource to explore the nature and uses of stem cells.

Stem cell potency A stern cell's ability to differentiate into different cell types is called potency. The greater the number of cell types it can differentiate into, the greater its potency. Stem cells can be separated into several : Totipotent stem cells: can differentiate into any type of cell in the human body, including the placenta. Zygotes and the 8 or 16 cells from its first few mitotic divisions are totipotent cells, which are destined eventually to produce a whole organism. Pluripotent stem cells: descend from totipotent stem cells and after several days, can differentiate into any type of cell except for totipotent stem cells. They are present in early embryos and arc the origin of the different types of tissue within an organism. Multipotent stem cells: descend from pluripotent stem cells and can differentiate into many cell lines within a specific type of tissue.  Haematopoetic stem cells in bone marrow are multipotent because this gives rise to the various types of blood cell. Unipotent stem cells: are a descendant of a multipotent stem cell and can give rise to a single cell type. (see http://www.explorestemcells.co.uk/ClassifyingStemCellsCategory.html for more detail on the different types of stem cell)

Differentiation Multicellular organisms like animals and plants have evolved from unicellular (single-celled) organisms because groups of cells with different functions working together as one unit can make use of resources more efficiently than single cells operating on their own. ln multicellular organisms cells have to specialise to take on different roles in tissues and organs. They may be required to form barriers such as skin or be motile such as sperm cells. Cells have adapted to different roles in an organism and so have many shapes and sizes and often contain different organelles. Erythrocytes (red blood cells) and neutrophils (white blood cells) are both present in blood. They look very different because they have different functions . When cells differentiate they become adapted to their specific role. What form this adaptation takes is dependent on the function of the tissue, organ and organ system to which the cell belongs. All blood cells are derived from stem cells in the bone marrow. Replacement of erythrocytes and leukocytes Mammalian erythrocytes are essential for the transport of oxygen around the body. They are adapted to maximise their oxygen-carrying capacity by having only a few organelles so there is more room for haemoglobin. Due to the lack of nucleus and organelles they only have a short lifespan of around 120 days. They therefore need to be replaced constantly. The stem cell colonies in the bone marrow produce approximately three billion erythrocytes per kilogram of body mass per day to keep up with the demand. Neutrophils have an essential role in the immune system. They live for only about 6 hours and the colonies of stem cells in bone marrow produce in the region of 1.6 billion per kg per hour. This figure will increase during infection.

Uses of stem cells Stem cells are currently used to treat cancers such as leukaemia. You may be familiar with the concept of bone marrow transplants, which have been used for decades now to provide a healthy source of cells in the body. Other diseases that stem cells may help include: heart disease- muscle tissue in the heart is damaged as a result of a heart attack, normally irreparably- this has been tried experimentally with some success already type 1 diabetes- with insulin-dependent diabetes the body's own immune system destroys the insulin-producing cells in the pancreas; patients have to inject insulin for life- this has been tried experimentally with some success already Parkinson's disease - the symptoms (shaking and rigidity) are caused by the death of dopamine-producing cells in the brain; drugs currently only delay the progress of the disease Alzheimer's disease- brain cells are destroyed as a result of the build up of abnormal proteins; drugs currently only alleviate the symptoms Stem cells are already widely used for treatment of conditions such as: the treatment of burns - stem cells grown on biodegradable meshes can produce new skin for burn patients, this is quicker than the normal process of taking a graft from another part of the body drug trials - potential new drugs can be tested on cultures of stem cells before being tested on animals and humans developmental biology - with their ability to divide indefinitely and differentiate into almost any cell within an organism, stem cells have become an important area of study in developmental biology. This is the study of the changes that occur as multicellular organisms grow and develop from a single cell, such as a fertilised egg - and why things sometimes go wrong.

Sources of stem cells Embryonic stem cells - these cells are present at a very early stage of embryo development and are totipotent. After about seven days a mass of cells, called a blastocyst, has formed and the cells are now in a pluripotent state. They remain in this state in the fetus until birth. Tissue (adult) stem cells - these cells are present throughout life from birth. They are found in specific areas such as bone marrow. They are multipotent. although there is growing evidence that they can be artificially triggered to become pluripotent. Stem cells can also be harvested from the umbilical cords of newborn babies. The advantages of this source are the plentiful supply of umbilical cords and that invasive surgery is not needed. These stem cells can be stOred in case they are ever Cord blood stem cells: this source of stem cells is derived from cord blood and is thought to hold enormous potential in treating disease. Stem cells are present in meristematic tissue (meristems) in plants. This tissue is found wherever growth is occurring in plants, for example at the tips of roots and shoots (termed apical meristems). Cells originating from this region differentiate into the different cells present in xylem and phloem tissues. In this way the vascular tissue grows as the plant grows. The pluripotent nature of stem cells in the meristems continues throughout the life of the plant.

The ethics of stem cells Stem cells have been used in medicine for many years in the form of bone marrow transplants. More recently, the use of embryonic stem cells in therapies and research has lead to controversy and debates regarding the ethics of such use. The embryos used originally were donated from those left over after fertility treatment. More recently the law in the UK has changed so that embryos can be specifically created in the laboratory as a source of stem cells. The removal of stem cells from embryos normally results in the destruction of the embryos, although techniques are being developed that will allow stem cells to be removed without damage to embryos. There are not only religious objections to the use of embryos in this way but moral objections roo - many people believe that life begins at conception and the destruction of embryos is, therefore, murder. There is a lack of consensus as to when the embryo itself has rights, and also who owns the genetic material that is being used for research. This controversy is holding back progress that could lead to the successful treatment of many incurable diseases. The use of umbilical cord stem cells overcomes these issues to a large extent, but these cells are merely multipotent, not pluripotent like embryonic stem cells, rhus restricting their usefulness. Adult tissue stem cells can also be used but they do not divide as well as umbilical stem cells and are more likely to have acquired mutations. Developments are being made towards artificially transforming tissue stem cells into pluripotent cells. Induced pluripotent stem cells (iPSCs) are adult stem cells that have been genetically modified to act like embryonic stem cells and so are pluripotent. Of course the use of plant stem cells does not raise the same ethical issues as animal cells but they are not as useful for treatment and research and animal stem cells because they have largely different properties and cannot be used to treat diseases in the same way that animal stem cells can.