3.11 - Stem cells and medical decisions

Self-renewal and differentiation

A stem-cell population can maintain a supply of stem cells while producing cells with specialised functions.

Self-renewal maintains the stem-cell supply through mitotic cell division. Differentiation is the development of a cell's specialised structures and functions. For example, a blood-forming stem cell can give rise to cells that become red blood cells, adapted to transport oxygen, or different white blood cells, involved in defence.

These are distinct properties. Producing more cells with the same specialised function is not, by itself, evidence of stem-cell identity. Equally, a cell that can become specialised but cannot maintain a stem-cell population does not supply a lasting source of stem cells.

A stem-cell division does not always produce one stem cell and one specialised cell. Depending on the signals and conditions, descendants may retain stem-cell properties or enter a pathway towards specialisation. Some stem cells remain inactive for long periods. Self-renewal describes their capacity; it does not mean that every stem cell is continuously dividing or that an individual cell survives for ever. These distinctions follow the NIH explanation of stem-cell properties.

During differentiation, different proteins and structures are produced. This normally involves changing which genes are active, rather than discarding all the genes that a specialised cell does not use. The detailed control of gene activity follows in the next lesson.

Potency and developmental range

Potency describes the range of cell types a cell can generate, rather than how quickly it divides.

Totipotency is the capacity to give rise to all the cell types needed for a complete organism, including the extraembryonic tissues that support development. The mammalian zygote, the fertilised egg, is the clearest example: its descendants can form both the embryo and supporting tissues, including the fetal contribution to the placenta. Development into an organism still requires a suitable environment.

Pluripotency is the capacity to give rise to all the specialised cell types of the body, but not by itself to the complete set of extraembryonic tissues and an entire organism. A pluripotent cell can therefore have very wide therapeutic potential without being equivalent to a zygote. This is the standard distinction used here; experimental studies of very early development require care about exactly what a cell has been shown to form.

Multipotent is useful for comparing tissue stem cells with pluripotent cells. A blood-forming stem cell does not normally generate every body-cell type: making several blood-cell types does not make it pluripotent. The NIH-hosted account of stem-cell potency distinguishes these developmental ranges.

As embryonic development proceeds, cell lineages generally become more restricted. Do not label every cell taken from any embryo totipotent. In particular, the embryonic stem cells commonly grown from the inner cell mass of an early embryo called a blastocyst are pluripotent. The cells contributing to the body and those contributing to supporting tissues have already begun to follow different lineages.

Sources of therapeutic cells

The source of a cell affects its developmental range and the practical and ethical questions surrounding its use.

Embryonic stem cells can be derived from the inner cell mass of a blastocyst and maintained as a pluripotent cell line. The original human embryonic stem-cell study established blastocyst-derived pluripotent lines. Conventional derivation involves using an embryo that will not then continue developing. This raises questions about the embryo's moral status and the consent of those who provided the eggs and sperm. One source is embryos donated after fertility treatment; donation must be a voluntary informed choice.

Adult stem cells, also called tissue or somatic stem cells, occur in tissues and help maintain or repair them. “Adult” distinguishes this category from embryonic stem cells; it does not mean these cells occur only in adults. Blood-forming stem cells can be obtained from bone marrow or blood, and blood stem cells can also be collected from donated umbilical cord blood after birth. Tissue stem cells usually have a more limited developmental range than pluripotent cells.

Induced pluripotent stem cells, or iPSCs, are made by reprogramming specialised cells, such as skin cells, into a pluripotent state. They are neither naturally occurring adult tissue stem cells nor cells taken directly from an embryo. The original human iPSC study demonstrated reprogramming of specialised skin cells and their ability to form different cell types.

Using a person's own cells can reduce some problems of immune mismatch. It does not remove every risk: cultured cells may change, be contaminated, or behave in an unwanted way. If the person has an inherited disease, cells made from that person's tissue may also carry its underlying genetic change. Reprogramming does not automatically correct it.

These sources are alternatives for particular research questions, not a simple ranking from bad to good. A restricted blood stem cell can be more appropriate for replacing blood production than an undifferentiated pluripotent cell. A source that avoids embryo use still requires donor consent and evidence for the proposed therapy.

Therapy benefits and biological risks

A cell-replacement therapy must restore a useful function, rather than merely put living cells into a patient.

In principle, stem-cell self-renewal provides a supply of starting cells, and controlled differentiation produces the required cell type. Transplanted cells must survive, reach or remain at the appropriate site, integrate with the tissue and function for long enough to benefit the patient. A nerve cell working in a culture dish has not yet been shown to form the right connections in a patient's nervous system.

An established example is blood stem-cell transplantation for selected blood cancers and other blood conditions. Treatment may involve chemotherapy, sometimes radiotherapy, followed by blood-forming stem cells from the patient or a suitable donor. The transplanted cells establish blood production in bone marrow and generate new blood cells. This can help treat or control the condition and restore blood formation after treatment. The NHS description of transplantation and its uses explain this specific application. It does not demonstrate that blood stem cells can repair any damaged organ, or guarantee a cure for every recipient.

Benefits must be weighed against the likelihood and severity of harm. Chemotherapy and reduced blood-cell production can leave patients vulnerable to infection and bleeding. In donor blood stem-cell transplantation, donor-derived immune cells may attack the patient's tissues: graft-versus-host disease. This is different from the recipient's immune system rejecting donor-derived cells. The NHS account of complications makes clear that an established therapy still carries risks.