Breakthrough in stem-cell harvest
SINGAPORE – Researchers here and in Sweden have come up with a way to harvest and grow human embryonic stem cells without killing the days-old embryo they come from.
The new method, considered a major breakthrough, will also allow scientists to mass produce high-quality, uncontaminated cells that can be used in the clinic, taking stem cells a step closer to the time when they can be harnessed to replaced damaged cells and cure serious illnesses.
“I believe that, with our methods, we have practically solved all technical issues around growing human embryonic stem cells, as well as addressing the ethical issue of killing the embryos,” said Professor Karl Tryggvason of Sweden’s Karolinska Institutet and Duke-NUS Graduate Medical School Singapore.
Human embryonic stem cells are master cells which can grow indefinitely and potentially generate all forms of tissue that the body needs, including brain, heart, liver, blood, skin and insulin-producing pancreatic cells.
The possibility that excites scientists and doctors about them is that they may one day be an inexhaustible source of replacement tissue to treat diseases ranging from the neurodegenerative disorder Parkinson’s disease, to heart and liver failure, diabetes and blindness. Such cells are also used as models to study disease.
However, a major stumbling block for such research has been ethical objections to harvesting the stem cells, which destroys the embryos they come from.
Another big problem was that existing embryonic stem cells did not thrive in the laboratory, and were contaminated with chemicals and animal nutrients used to grow them.
What works in the petri dish often does not have the same results in patients because the new environment is so alien, said Prof Tryggvason, 66, a clinician-scientist who moved to Singapore in 2012.
“This is a big problem in science, and it’s also a big reason drug companies looking at new potential cancer drugs developed in-vitro couldn’t repeat nine in 10 of the earlier experimental results, even though they made it to top journals.”
His breakthrough centres around four decades of dogged research into an “unsexy” matrix of cells and proteins which have, until recently, been overlooked by scientists.
These are connective tissues called basement membranes which anchor and support all the body’s tissues, and are made up of proteins called laminins.
Initially thought to be homogeneous throughout the body, there are actually many types of laminins responsible for cell differentiation, adhesion, anchorage, survival and regeneration, for instance.
“This is a new field in cell biology – we now know that ‘The Matrix’ is everywhere, it is all around us,” said Prof Tryggvason, making a joking reference to a quote from the film of the same name.
In 2012, he received the Singapore Translational Research Investigator Award from the Singapore Ministry of Health’s National Medical Research Council, an award worth $9.5 million over five years.
Together with colleagues at Karolinska, he developed a cocktail of laminins which make the stem cells feel at home in the laboratory.
Specific types of these fibrous proteins are normally found together with stem cells in the embryo as it starts developing.
Growing the stem cells on laminins meant that they thrived and, within a few days, researchers had culture plates full of 99 per cent pure embryonic stem cells.
This paved the way for the team’s second breakthrough: Because the laminin environment was so “fertile”, the group was able to create a stem cell colony from a single cell taken from the eight-cell embryo.
Taking just one cell from each surplus in-vitro fertilised embryo means that it can be re-frozen and implanted. A similar procedure is already done during pre-implantation genetic diagnosis, where tests are done on a single IVF embryo cell to uncover genetic diseases, said Karolinska Institutet. If no mutations are found, the embryo is then placed in the woman’s uterus.
“We know that an embryo can survive the removal of a single cell. This makes a great ethical difference,” noted Prof Tryggvason.
The team’s work was published recently in the journal Nature Communications.
Taking the work a step closer to the clinic, fellow researchers at Duke-NUS have also been able to grow heart muscles in the lab, and use them to treat heart injury in rats.
Other groups across the island are covering the entire spectrum of stem cell research, from discovering stem cells responsible for the uncontrolled proliferation of cancers, to prodding them to become various different cell types.
Prof Tryggvason envisions stem cell banks where such cells can be matched by tissue type so patients do not reject any transplants.
“A stem cell bank could mean that, in the future, these cells could be stored for use. Imagine the limitless possibilities of their use in regenerative medicine.”
Source: Asia One
Published: 04 Mar 2014
