What makes bone marrow such a versatile resource for curing human diseases?

This essay was written by Thomas Elliott and was first published in the 2010 Mill Hill Essays.

Marrow is not the most exciting of tissues. Soft and fatty, hidden away within lifeless bones, it is easy to overlook. Yet bone marrow is at the cutting edge of a remarkable and growing list of disease therapies ranging from the treatment of cancer to the repair of damaged hearts. What, then, lies beneath this surprisingly versatile tissue and its applications in modern medicine?

Belying its dull appearance, bone marrow is a thriving hub of new life. Indeed, the clinical use of bone marrow reflects its astonishing role as a vehicle for regeneration in the healthy body. Cell death is a natural occurrence and because it happens in the body at a ferocious rate it must of course be balanced by an equally prodigious rate of cell birth. Red blood cells, for example, die at a rate of 2 million every second and are replaced precisely by the creation of new cells within the bone marrow. This requirement for renewal on a massive scale is true of most blood cells; the neutrophils of the immune system are produced at a rate of about 100,000 million per day. At the heart of this renewal process is the stem cell. During repeated rounds of cell division not only is the stem cell population replaced, but any of a variety of different types of cell, each with significantly different functions, may be produced: red blood cells, white blood cells and platelets. It is thus both the number and diversity of cells produced by the bone marrow that forms the basis of its broad medical application.

There are two basic forms of bone marrow transplant. An autologous transplant is one in which cells are removed from a patient and returned later. This is often necessary where blood cells are likely to be damaged during a medical treatment such as chemotherapy or radiotherapy. By replacing healthy bone marrow after the treatment is finished, a speedy recovery is ensured. In contrast, allogeneic bone marrow transplants are those in which marrow is donated from one person to another. While the procedure is much the same, a number of criteria must be met to keep the procedure safe. For example, the tissue type of the donor must match that of the patient. Whilst tissue matching is normally required to prevent rejection of a graft, in the case of bone marrow there is also the risk that, unless the match is good, donor immune cells attack the new host in a condition known as graft-versus-host disease, which can have very serious consequences. Bone marrow transplantation is a dangerous and complicated task, but the benefits often outweigh the risks.

Leukaemia, a cancer of the blood or bone marrow caused by uncontrolled division of white blood cells, is one of the most common diseases treated by bone marrow transplantation. High dose chemotherapy or radiotherapy is first applied to kill rapidly multiplying cancer cells, but this inevitably also destroys a large proportion of the patient’s healthy immune system and stem cells, leaving the patient anaemic and vulnerable to infection. Bone marrow is therefore transplanted from a healthy donor, leaving the stem cells within the graft to divide and repopulate the patient’s supply of blood cells. For example, multiple myeloma is a cancer of antibody-producing cells of the immune system and is at present incurable, but survival can be extended using bone marrow transplants. Other cancers may be treated in a similar manner due to the plasticity of bone marrow stem cells, including myelogenous leukaemias of cells that usually give rise to red blood cells. Allogeneic transplants have the potential to be curative as the bone marrow is entirely healthy; hence they can be used as rescue treatments where bone marrow has already been destroyed, by cancer or otherwise.

Bone marrow transplantation is clearly beneficial for conditions in which cell growth is excessive, abnormal and uncontrollable, yet it is equally applicable for illnesses in which our bone marrow does not produce enough of a desired cell type. Sickle cell anaemia is a disease in which red blood cells are abnormally curved; it is potentially fatal. One recent study reported a high success rate when treating adult sickle cell patients with bone marrow transplants as donor marrow is able to produce healthy, disc-shaped red blood cells. Similarly, patients with thalassaemia suffer from disproportionate destruction of red blood cells, leading to anaemia. In these cases, particularly among children, a transplant can lead to a huge increase in the quality of life. The same is true of aplastic anaemia, a rare bone marrow disease characterised by insufficient production of mature red and white blood cells.

These well-established procedures just scratch the surface of the exciting capacities of bone marrow stem cells to produce blood cells and other tissues, as we have only recently begun to discover. Take the example of Claudia Castillo, who in March 2008 was the world’s first recipient of a windpipe transplant partially constructed from her own cells. This was achieved by combining stem cells extracted from her bone marrow with a section of donor windpipe stripped of its cells using digestive enzymes. Indeed, the use of adult stem cells for organ regeneration and repair is a key area of development. In April this year, it was reported at the American Heart Association conference that a team had grown full, working blood vessels from bone marrow stem cells, presenting new opportunities in bypass surgery where no suitable vessels are available.

The potential of bone marrow stem cells in medicine is immense; the great expansion in research and interest over the past decade suggests that developments will continue to emerge. Unlike foetal stem cells, plagued by problems of availability, rejection and ethics, adult stem cells found in bone marrow are fast emerging as the most versatile and effective responses to human disease – to rescue, recover and regenerate.

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