Stem Cells

What is a stem cell?

Most cells in your body are specialised: a red blood cell carries oxygen, a neuron carries impulses. Specialised cells usually cannot change type. Stem cells are the "raw material" that replace them.

The two key characteristics are:

• Self-renewal: they divide again and again, producing more stem cells.

• Differentiation: when signalled, some daughter cells become specialised.

Potency and sources

Potency describes how many cell types a stem cell can become.

Sources fall into two groups:

• Embryonic stem cells: taken from a blastocyst (an early embryo of about 5 days), usually from spare embryos left over from IVF. Pluripotent.

• Adult (somatic) stem cells: found in tissues such as bone marrow, skin, and the lining of the gut. Multipotent. Umbilical cord blood is also a source of multipotent cells.

How cells with the same genome become different

Almost every cell in your body has the same genome: the same DNA. Yet a neuron and a muscle cell look and behave very differently. The reason is gene expression: in each cell type, only some genes are switched on (transcribed and translated) and the rest are switched off.

• A neuron expresses genes for ion channels and neurotransmitters.

• A muscle cell expresses genes for the proteins actin and myosin.

• A developing red blood cell expresses the gene for haemoglobin before it loses its nucleus (a mature red blood cell has no DNA).

Differentiation is therefore a change in which genes are active, not a change in the DNA sequence. Signals such as hormones and growth factors, and epigenetic changes to chromatin, switch genes on or off.

This explains potency. A pluripotent cell has a very wide range of genes available to be switched on. As a cell differentiates, more and more genes are switched off, often stably, so a multipotent cell has a narrower range and a fully specialised cell has a fixed pattern.

Stem cells in medicine

Stem cells can be used to regenerate damaged tissue. Stem cells are grown in the lab, directed to differentiate into the needed cell type, and then placed in the patient.

• Bone marrow transplant: multipotent haemopoietic stem cells in the bone marrow make all blood cells. In leukaemia, the patient's diseased marrow is destroyed and replaced with a donor's stem cells, which rebuild healthy blood. The donor must be closely matched (tissue type, HLA markers on cell surfaces) so the patient's immune system does not reject the cells and the donor's white cells do not attack the patient.

• Skin for burn victims: skin stem cells are cultured to grow sheets of new skin.

• Possible future treatments: replacing neurons lost in Parkinson's disease, or insulin-producing cells in diabetes.

Risks include rejection by the immune system, cells dividing out of control and forming tumours, and infection during treatment.

Embryonic stem cells are of more interest for a wide range of conditions because they are pluripotent and can be directed to become almost any tissue, whereas adult stem cells are multipotent and limited to a few cell types.

Cloning and induced pluripotent cells

Therapeutic cloning aims to produce stem cells that match a patient.

1. Take a somatic (body) cell from the patient and remove its nucleus.

2. Remove the nucleus from a donor egg cell (enucleation).

3. Transfer the patient's nucleus into the enucleated egg.

4. Stimulate the egg to divide and grow into a blastocyst.

5. Harvest the embryonic stem cells from the blastocyst and direct them to differentiate.

Because the nuclear DNA comes from the patient, the cells carry the patient's cell-surface markers and are unlikely to be rejected.

In reproductive cloning the embryo is implanted into a uterus to develop into a whole new individual (as with Dolly). In therapeutic cloning the embryo is never implanted; it is used only as a source of cells.

An alternative that avoids embryos is induced pluripotent stem cells (iPS cells): ordinary adult cells (such as skin cells) are reprogrammed by switching on a few key genes, so they become pluripotent again. They can be made from the patient, so rejection is unlikely, and no embryo is destroyed.

Ethical issues

Science can tell us what can be done and how. It cannot, on its own, tell us what should be done. Ethical judgement depends on values.

Alternatives such as iPS cells and adult stem cells reduce some objections, though they have their own risks and limits.

To evaluate a question like "should this research be permitted?", scientific knowledge supplies the evidence (how effective, how safe, what alternatives exist), while ethical judgement weighs the moral status of the embryo, benefits against harms, and what society values. Laws and regulation come from combining both.

Summary

• A stem cell is unspecialised, shows self-renewal and can differentiate.

• Potency: totipotent (all cells plus placenta), pluripotent (almost all body cells), multipotent (a few related cell types).

• Embryonic stem cells (blastocyst) are pluripotent; adult stem cells (e.g. bone marrow) are multipotent.

• Differentiation is a change in gene expression, not in DNA content; Dolly showed that differentiated cells keep the full genome.

• Uses: bone marrow transplants (donor must be closely matched), skin grafts, possible future therapies. Risks: rejection, tumours.

• Therapeutic cloning uses a patient's nucleus in an enucleated egg to make matching cells; reproductive cloning produces a new individual and is widely opposed. iPS cells avoid embryos.

• Science gives evidence; ethics weighs values. Both are needed to decide policy.

Back to the start: bone marrow contains multipotent haemopoietic stem cells that self-renew and differentiate into all blood cells, which is why a closely matched donor's cells can rebuild a leukaemia patient's blood.