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How safe are U.S. approved cell lines?

Prof. Bongso has identified 500 new genes found in embryonic stem cells but missing in adult cells. Finding a gene or two that controls the formation of organs can change the course of medicine.

Use of human feeder keeps embryonic stem cells undifferentiated for nine days instead of seven days as in the case of mouse feeder. This produces four times more cells per generation.

TEN TO fifteen years from now, Nobel Prize for Medicine could be awarded to Professor Ariff Bongso who is now a Research Professor with the Department of Obstetrics & Gynaecology, National University of Singapore. And his achievement — identifying embryonic stem cells (ESC) and help bring about a paradigm shift in the way some diseases would be treated in future. No medicines or major surgery, just an insertion of stem cells into the affected organ and behold! The disease is not merely treated but cured forever.

Embryonic stem cells have become the elixir for many suffering from Parkinson's, Alzheimer or diabetes, to name a few, for which dreaming of a cure (now) is akin to chasing a mirage. For the uninitiated, stem cell is the `mother of all cells'. They are the undifferentiated cells that when programmed with genetic instructions can alter themselves and grow to become any specialised type of cell in the body.

Identifying human feeder

Identifying stem cells was no flash-in-the-pan event for Prof. Bongso. He has left his footprints in the field of assisted reproduction many a time. And identifying stem cells was only a natural progression to his many earlier discoveries. "Idea came like a flash that stem cells came from five day old embryos," Prof Bongso recalled. His latest achievement has been the development of a xeno free (read animal free) medium to grow the stem cells. Till then mouse feeder was routinely used and all the 78 cell lines approved by the National Institute of Health, U.S. (for funding) have been grown on mouse feeder.

"The cell lines grown on mouse feeder have a chance of getting contaminated (with pathogens) as the stem cells are in direct contact with the mouse feeder," Prof. Bongso said. "It dawned on me based on my clinical experience that use of mouse feeder was not right and I was determined to find a way to do away with it and instead use human cells as feeder". This determination made him revisit his earlier work of 1994 where he had used human cells as feeder to isolate stem cells.

The year 1994 saw the medical community gain through Prof. Bongso's work. But little is known about the loss it suffered and the eight years it lost in this vital area. "I had then used fallopian tube cells as a medium and was able to grow stem cells up to two generations. But I was not able to go beyond that," he recalled.

Tasting success by using fallopian tube cells was in a way his undoing. It probably restricted him from looking at other human cells as a potential source "I got stuck to fallopian cells and probably missed trying the other human cells as feeder," Prof. Bongso revealed. And he missed the bus.

James Thompson of the University of Wisconsin who was also working on stem cells felt that using human feeder was the problem in growing more stem cell generations. He made the switch to mouse feeder as he was working on mouse stem cells and was able to grow up to 30-40 generations. And the use of mouse feeder came to stay.

Prof. Ariff Bongso

One reason why he did not identify a better human feeder much earlier was his decline in enthusiasm with stem cell research. "This was because no scientist saw potential in stem cell research and start working on it after I identified them. After all, a scientist gauges his work based on the enthusiasm other scientists show in carrying forward his research work," he lamented. The ethical issue also continued to trouble stem cell research.

Interest was rekindled and his passion was ignited in 1998 when Dr. Thompson found a way of growing stem cells for 30-40 generations. In less than two years he and Alan Trounson of the Institute of Reproduction and Development, Monash University, Australia, were able to grow cell lines and grow neurons too using human feeder. Neurons grow when the stem cells have reached approximately the 22{+n}{+d} generation.

Having successfully created a human feeder to grow stem cells and thereby shrinking the time taken to take stem cell research to clinical investigation, he is least interested in growing tissues from stem cells. "I am not a tissue maker. I am more interested in fundamental research and in understanding and unravelling the genetic secrets that direct the stem cells to form tissues," he asserted. "Of course my approach is only complementary and the end purpose is the same — produce tissues."

True to his assertion Prof. Bongso has already identified 500 new genes found in the embryonic stem cells but missing in adult cells. "If we can hook on to one or two genes that control the production of islets of Langerhans (cells which produce insulin) or any other tissue then we have hit a gold mine," he said with optimism.

Saying no to adult stem cells

He is fascinated by stem cells but it is only the ESCs and not the adult stem cells that interest him. "Embryonic stem cells have an edge over adult stem cells as they can differentiate into any of the 210 cell types found in our body," he reasoned out. Moreover, adult stem cells cannot form cell lines. In short adult stem cells cannot be used to treat other individuals unlike embryonic stem cell lines. "This restricts their use. They can be used to treat only the individual from whom the adult stem cell has been taken," he elaborated.

This limitation apart, it has been recently found that adult stem cells tend to form new tissues through diffusion unlike ESCs that form tissues through differentiation. Tissues formed by diffusion tend to have double the number of chromosomes. "This finding has hit the adult stem cell research hard," he noted.

Similarly, he is not in favour of therapeutic cloning to produce tissues. "It's a very inefficient process. We need eggs for the process and this is a precious commodity. And more than hundred eggs are required to produce one successful procedure," he stressed. Finally the possibility of transferring the fertilised egg in to a womb will result in reproductive cloning and he fears that a maverick can resort to this. "I would like to get into an area where benefits are realised in the shortest possible time.

Prof. Bongso is in a hurry and nothing can stop him now. From helping infertile couples have babies to find the elixir that would cure diseases, Prof Bongso has come a long way. Money does not interest him. Nor does fame. May his tribe increase in number.

R. Prasad

recently in Singapore

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