Stem cells and cell therapy

"Stem cells" are the new favorite of the popular media. How is it that this term has come to symbolize the dawn of an era in medicine?

In the US alone, there are 16 million diabetics including many hundreds of thousands of children, over 1 million Parkinson's disease sufferers, over 4 million with Alzheimer's disease and nearly 5 million with congestive heart failure. These raw statistics mask much personal tragedy: a child afflicted for life with Type 1 diabetes, the legions who suffer the degrading and debilitating effects of neurodegenerative diseases such as Parkinson's and Alzheimer's, the many weakened by failing hearts. Missing completely are figures for the relatives, and friends, who suffer alongside and shoulder the burden of their loved ones care.

Macular degeneration in the eye, Huntington's disease, congestive heart failure, motor neuron disease, are other terrible afflictions that have been mentioned as good targets for stem cell therapy, but what is stem cell therapy? Is it new? And, most importantly, will it work?

The human body is made up of over 200 distinct cell types, organized into specific tissues and organs. During adult life, these tissues and organs undergo wear and tear and require a constant supply of replacement cells. In many cases, this maintenance function is fulfilled due to the unique activities of adult stem cells. Stem cells can undergo cell division to renew their cell numbers and under certain circumstances, they will mature into a number of different, specialized cell types. There are many different types of stem cell, each restricted in the types of specialized cell it can give rise to; for example, there are blood, neural, liver and skin stem cells. At any time, stem cells numbers in the body are very low making these cells extremely difficult to identify and purify. In addition, many stem cell types do not grow well in culture where they also often lose their distinctive cellular properties. These particular attributes are not shared by embryonic stem cells. These cells do not occur in the adult, nor in fact, even in the embryo. They are artifacts of the laboratory culture of disrupted, early stage (4-5 day) embryos from some mammalian species. Unlike adult stem cells they are easy to obtain pure and relatively easy to cultivate in large numbers.

In recent years, research on adult and embryonic stem cells has burgeoned, driven in part by fervent hopes of public and scientists alike, that these cells can be manipulated to provide cellular therapies for a variety of debilitating human diseases. Cell therapy is not new. In the 17th century, sheep blood was transfused into human patients. Although these transfusions did not work, human to human blood transfusions became a well established procedure in the early 20th century after Landsteiner's discovery of the major human blood types. The most important cellular components in routine blood transfusion are the differentiated erythrocytes. In recent times, other cellular preparations, including cultured chondrocytes ( Carticelc) and dermal fibroblasts (Dermograftc) have become available. Stem cell therapy is also not new; bone marrow transplantation which was first used clinically in the 1960s, is in fact blood stem cell transplantation, and is still used to treat various serious blood diseases. The finding that such stem cells can be found in umbilical cord blood and can be used to cure sick children (1988), has led many parents, determined to safeguard the long term health of their children, to bank cord blood after the birth of each child. In the future, when we talk about cell therapy, we should recognize that this could involve stem cells or any of their more specialised progeny, including the "intermediate" progenitor cells. Moreover, these cells can be obtained directly from human donors or entirely generated through laboratory culture.

It was two breakthroughs near to the turn of the last century which truly provoked the current excitement over stem cell research. The first, in 1997, was the cloning of Dolly the sheep in Scotland. Her origins lay in an adult mammary cell not in a newly fertilized sheep egg. What made Dolly so special was that her creation shattered the long-standing view that the genetic programs at work in adult cells were fixed and unalterable The second major breakthrough came in 1998 with the generation in of stable human embryonic stem cell (hES) lines by the USA's Jamie Thomson and his team. They provided a new type of human stem cell, one that, in principle, could be used to make any type of replacement tissue desired.

The two technologies could be combined to make customized hES cells that are immunologically identical to the patient thereby avoiding the problems of tissue rejection that often accompany clinical transplantation. This concept is often referred to (unhelpfully) as therapeutic cloning. An alternative and more immediate use of the merged technologies is to prepare hES lines from the nuclei of diseased cells such as the neurons from patients suffering from Alzheimer's or Lou Gehrig's disease. These hES cells could provide an inexhaustible supply of specific disease-affected neurons for drug discovery. Very recently, it has proved possible to directly convert adult mouse skin cells into cells that appear to have most if not all the properties of embryonic stem cells. If this work could be extended to human cells, it could provide a much simpler, uncontentious, way of providing customized hES cells

The remarkable developments above have been accompanied by an avalanche of scientific claims regarding the magical abilities of different types of adult stem cells to interconvert and form all sorts of unexpected tissues. Although many of the claims have had to be revised in light of new information and better experimental design, there remains considerable hope that adult stem cells will provide novel cell therapy products in the future. It is unfortunate that some people are determined to push for a moratorium in hES cell research as a result of biased and flawed claims that the less ethically contentious adult stem cells offer a complete answer. The truth is that all types of human stem cell research should be pursued in parallel in order to facilitate maximum progress. The likelihood is that cell therapy cures will emerge from all stem cell sources on a case by case basis. Although, there are all sorts of challenges, regulatory and technical, before these new therapeutic modalities achieve broad recognition and acceptance, the question is not "if" but "when".