Tissue regeneration and tissue engineering are two strategies to fight the diseases of old age

This is what Professor Rudolph Jainisch from the MIT Biology Department, an international expert in the field of stem cells, said in a lecture at the Biomed 2009 conference.

This is the eighth year in a row of holding the Life Sciences and Technology Week in Israel, which takes place side by side with the international meeting of stem cells. Dozens of biomedical companies from all over the country come to present their wares - in devices and intellectual goods - and hundreds of scientists and researchers participate in lectures on biology, medicine and the combination of the two.

After the routine opening speeches by Shimon Peres and Benjamin (Fouad) Ben-Eliezer, the more scientific speeches began to unfold. Since the international meeting of stem cells is primarily an academic conference, the scientific lectures delivered in it reflect the progress of science in the field in recent years, and predict the directions of progress in the years to come. Important scientists from the field of life sciences flaunt their intellectual wares in front of the knowledge-thirsty public, and reveal bits (and always, hide bits) of the advances made in their laboratories. It is not for nothing that many start-up companies send their best employees to academic conferences, so that they can learn where the wind blows in the research laboratories.

Indeed, the very first scientific lecture at the conference did not disappoint. Professor Rudolph Jainisch from the MIT Biology Department, an international expert in the field of stem cells, chose to share with the audience the future of embryonic stem cell research, and the revolution the field is undergoing thanks to the recent invention of induced stem cells.

Paradoxically, the fact that the average life expectancy has increased in the last hundred years provides the biggest problem in medicine today. The increasing age of the population has resulted in an increasing number of old age diseases such as Alzheimer's, Parkinson's and cardiac problems. Two of the possible solutions to these diseases are tissue regeneration and tissue engineering, but both involve transplanting cells inside the body. And like other expensive commodities, cells - or at least heart cells and nerve cells - do not grow on trees.

The most talked about source of replacement cells today is embryonic stem cells. These cells are able to differentiate and create any of the different types of cells that exist in the body. In principle, these cells can be used to restore the cells that have degenerated in degenerative diseases. The main goal of stem cell research, according to Yeinisch, is to provide suitable cells for tissue repair. But, he adds, we're pretty far from that right now.

The main problem with embryonic stem cells is that they are derived from embryos that have been donated to science. Each cell that is produced from these stem cells will carry immune markers corresponding to the embryo from which it came. These cells will be rejected by the transplanted immune system, which will attack any cell that does not carry the immune markers of the body's cells. Because of this, embryonic stem cells in their rawest form are not relevant to disease treatment.

The solution to the problem of immune rejection may come in two different ways. The first way is creating a clone - transferring a nucleus from a human cell into a human egg, and creating an embryo with a genetic code identical to that of the nucleus donor. From this embryo it will be possible to produce embryonic stem cells, which will undergo appropriate differentiation into the necessary tissues. All the cells produced from this embryo will have the same immune markers as the original nuclear donor, and therefore they can be transplanted into his body when necessary. This solution is acceptable in mice, but as of today it is not yet applicable in humans due to technical problems. It is important to explain that there is not necessarily an ethical problem here, because the 'embryos' are nothing more than globules of cells containing several thousand cells. They do not have organs or even basic tissues such as muscles or nerves. In fact, their level of complexity at this stage is lower than that of some of the cancerous tumors that can be found.

The technical problem of using embryonic stem cells has been solved through the recent success in producing an exciting new type of stem cells: induced stem cells (IPS). In 2006, Takashi and Yamanaka showed that it is possible to take fibroblast cells - cells found in the skin - from a mouse, and insert into them four genes that are particularly active in embryonic stem cells. These genes undergo increased expression within the fibroblasts, returning them backwards in time to the state of embryonic stem cells, which are able to redistribute to any other cell in the body. Not only that, but these cells can even join the embryo creation process, if they are injected into a young mouse embryo. Similarly, it is possible to take cells from a person, turn them into induced stem cells, sort them into the desired tissues and use them for a multitude of purposes: for transplantation in the body instead of degenerated cells, for understanding the mechanisms of action of diseases, the effect of drugs on cells, and more.

Despite the great potential of induced stem cells, technological problems still exist, especially in growing stem cells on a commercial scale. The stem cells, whether they are embryonic or induced, differentiate very easily into other cells, and it is very difficult to direct and direct the direction of their differentiation. Stem cells that were supposed to differentiate into nerve cells, for example, may also differentiate into muscle, cartilage and bone cells if grown under the wrong conditions. There is no need to explain why most Parkinson's and Alzheimer's patients would prefer not to have such a jumble of cells injected into their brains. The trouble is that we still do not understand the language that the stem cells speak. A good example of the difficulty in controlling differentiation comes from Bob Langer's lab, where researchers recently demonstrated that even the polymers that make up the growth surface of the cells in the lab can affect the direction of their differentiation.

Although there are other problems with the induced stem cells, Yeinish announced that most of them have been solved, or will soon be solved. The Achilles heel of human stem cells in the past was that it was very difficult to carry out genetic engineering in them. This problem is currently being solved through the use of a new technology called ZNF, which may allow the introduction of genes into human stem cells, and even correct genetic diseases in these cells. Another problem with induced stem cells was - and still is - the fear of disrupting the genetic code of the cell to the point of creating a cancerous tumor. But new techniques for inserting the genes into the induced cells are slowly dispelling the fear.

How will medical research be conducted in the future? "If we want, we can take cells from a person with ALS [muscular dystrophy, RA], sort them into motor neurons, compare them with cells from a normal person who have undergone the same process, and watch when the amyloid bodies form in the ALS cells. On the cells, we can try drugs that slow down or prevent neurodegeneration." said Jainish. In this way, we can discover cures for many diseases, by acting on the original diseased body cells - outside the body. On this optimistic note, the Biomed conference and the third international meeting of stem cells opened.

Reporting from the field - Roi Tsezana.