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Singapore scientist makes stem cell research advance

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    Singapore scientist makes stem cell research advance

    Singapore scientist makes stem cell research advance

    .c Kyodo News Service


    A scientist in Singapore has succeeded in growing human embryonic stem cells without any exposure to non-human animal cells, marking a major breakthrough in stem cell research, the company that funded the research announced Monday.

    The new technology will make it possible to offer stem cell lines, which are free of materials derived from non-human animals, and thus suitable for use in clinical trials, said ES Cell International, an Australia-based Singapore company with majority government ownership.

    The research will be published in the September 2002 edition of Nature Biotechnology, the most respected scientific journal in the field, which is published in the United States.

    The team of researchers led by Ariff Bongso, a research professor at the National University of Singapore (NUS), conducted their trailblazing research at the university.

    The 56-year-old Sri Lankan-born Bongso, who has been a Singapore citizen for the last 16 years, said the methodology will be refined further by the U.S. Food and Drug Administration for the creation of additional cell lines for clinical application.

    Stem cell lines supported by non-human animal-derived materials pose the risk of transmission of pathogens from the non-human animal feeder cells to the human embryonic stem cells.

    Stem cells promise hope of a cure for diseases such as Alzheimer's and diabetes in the future.

    Singapore is striving to be a hub for biotechnological research, especially stem cell research.

    08/05/02 01:51 EDT

    Stem-cell pioneer excited about latest coup
    NUS' Ariff Bongso and team make major breakthrough, creating cells that are fit for human transplant
    By Salma Khalik

    PROFESSOR Ariff Bongso has been disturbed by the thought of using embryonic stem cells grown with animal tissues in humans.

    In 1994, he became the first researcher in the world to isolate embryonic stem (ES) cells. p> Yet, despite his pioneering achievement, he was unhappy that the ES cells were unable to grow beyond two generations on a human feeder system, the base layer on which the cells are grown.

    'I thought it would be a nice idea to find out why. Was it the feeder? Was it the culture medium? Was it something mechanical?' said the Sri Lankan-born researcher, who came to Singapore in 1986.

    However, the problem is now behind him as he and his team have finally been able to create cells that are fit for human transplant.

    This is Prof Bongso's third major breakthrough.

    In 1991, he hit the headlines when he developed a method known as co-culture to help infertile couples conceive, a method used widely today.

    This was followed by his 1994 success with isolating ES cells.

    Both times, he presented his findings to the scientific community, but without first patenting his work.

    In 1997, an American team obtained a United States patent for growing ES cells. The following year, Prof Bongso and his team got a patent for the rest of the world.

    Learning from his earlier mistakes, he has filed a patent for his latest research.

    This work was driven by comments from the United States Food and Drug Administration that it was not comfortable about the current method of growing cells with animal input.

    The soft-spoken research professor at the National University of Singapore said: 'This point is central to all my work.

    'If the existing system is animal-based and someone comes up with a method to grow pancreatic cells for diabetes, it's useless, because it cannot go on to clinical application.'

    The problem kept gnawing at him. He said: 'Even when I went to bed, I still kept thinking about it.'

    So, in 2000, with funding from ES Cell International, a company partly-owned by the Singapore Government, he and his team - Mr Mark Richards, Dr Fong Chui Yee and Mr Chan Woon Khiong - started their research.

    They used fallopian tubes, as well as muscle and skin from both adults and foetuses, to grow different human feeders.

    They also worked on human nutrients, derived mainly from blood serum and plasma. The nutrients are a cocktail of protein, insulin and other ingredients to furnish the right mix of liquid to cover and nurture the cells.

    The team tried various combinations before getting a mix that ensured the stable growth of ES cells.

    'It was very difficult to grow muscle and skin feeders, but they were the best,' said Prof Bongso.

    'One of our achievements is our ability to grow the feeder cells.'
    One thing the team discovered early on was that the human ES cells were 'groupies' - they needed to live in colonies.

    Prof Bongso's earlier experiments had failed because he had used single cells.
    Another problem the team had to overcome was that when grown on human feeders, the very thin layer of ES cells tore very easily. The thicker layers grown on mouse feeders were more hardy.

    Mr Richards, who undertook a lot of the physical work in the laboratories, said he had to be very gentle when dividing the cells.

    He had to break up clusters of cells to form smaller colonies. These were placed into fresh dishes to grow the next generation of cells.

    In the end, the human feeder and nutrient combination proved to be far superior to the animal equivalent.

    The ES cells remained undifferentiated for nine days, instead of the normal seven, giving four times as many cells per generation.

    Once the cells start to differentiate into any of the 200 cells found in the human body, they no longer retain their potential and have to be discarded.

    Mr Richards recalled the exhilaration when Prof Bongso declared the experiment a success in October last year.

    All along, the team had been working with ES Cell International's six existing ES cell lines. Now, it wants to produce a new line grown entirely on a human feeder and nutrient combination - to prove conclusively it could be done.

    Associate Professor P.C. Wong, who heads the National University Hospital's obstetrics and gynaecology department, obtained permission from parents to provide the team with a few days' old embryo that would otherwise have been discarded.

    The team has successfully grown the 30 to 40 ES cells it obtained from the embryo for more than 40 generations.

    Prof Bongso sees his latest achievement as his biggest coup.

    Looking back at his work with co-culture and isolating ES cells, he said: 'When you make a discovery, you think 'I am the first in the world, I've found it!' '
    This time, however, it was different.

    'Here, the excitement is because we're cleaning up the system.

    'We're refining it and it's working. We've moved closer to clinical application.'

    But he confessed that the research has taken a toll on his personal life.
    It's been very stressful, he said, competing with others in his field.

    The father of two grown-up children has even considered retiring.
    But then he smiles and remembers how much more there is to do.

    'You always think, 'I'm now going to give this a rest'. And then it dawns on you that there is another interesting area here. So you say, 'I'll give it a go and then I'll retire'.'