Advances in Sweden’s Human Embryonic Stem Cell Research
Thursday, 26 August 2004
Sweden has a leading global position in stem cell research. More than 30 research groups and 300 people at nine Swedish institutions are involved in stem cell research, aiming to address serious diseases that today lack curative treatment, notably neurological diseases, heart failure and diabetes. Moreover, with a favourable legislative environment supporting all areas of stem cell research, including therapeutic cloning, Sweden is already today one of the world’s largest holders of human embryonic stem cell lines.
In two articles to be published in September issue of Reproductive BioMedicine Online, the major Swedish groups studying and developing hESC lines describe their latest advances. Prof. Lars Hamberger's groups at the Sahlgrenska University Hospital in Gothenburg describes in some detail the quality of fresh and frozen–thawed embryos that were cultured to the blastocyst stage. Twenty-two hES cell lines were derived from 114 blastocysts, giving an overall success rate of 19.3%. They further showed that derivation of ESC lines from previously frozen embryos were up to 4 times more effective than with fresh embryos. Together with the stem cell company they have formed, Cellartis AB, there are now more than 30 hES cell lines available from this group to be distributed worldwide.
However, this private initiative has run into some problems recently. In the proposal for a new legislation on human stem cells and therapeutic cloning in Sweden, the government recently deleted a part of the text supporting the marketing of unidentified human embryonic stem cells. They had earlier been heavily criticised for planning to allow buying and selling of human cell lines by private companies.
This is "...devastating" said Anders Vedin, chairman of Cellartis AB.
"It has always been clear the difficulty to charge human biological material," Vedin said in an interview with Ny Teknik earlier this summer.
"But if it’s not possible to compensate for the costs and increased know-how from the users, ... it is to side-step the whole idea of patenting," Vedin said further.
Harriet Wallberg-Henriksson, principal at Karolinska Institute, said:
"I can understand the government’s position. But I hope they come up with a solution quickly. If Sweden wants to be a driving force in biotechnology, you have to be able to commercialise the science results."
Professor Outi Hovatta’s group at the Karolinska University Hospital at Huddinge, Stockholm, tries to find optimal culture condition for the derived hESC lines and how to keep them in an undifferentiated state. To this end they have refined the composition of a growth medium for hESCs. They have previously developed a system of human foreskin fibroblasts as feeder cells for the derivation and continued undifferentiated growth of hESCs.
The hESCs proliferated fastest when 20% of serum replacement (SR) was used. In human serum-containing medium, the cells underwent extensive spontaneous differentiation within a few passages. Foetal calf serum supported the non-differentiated growth poorly. Basic fibroblast growth factor supported non-differentiated growth, the highest concentration (8 ng/ml) giving the best result. Addition of an insulin–transferrin–selenium (ITS) mixture to the cell cultures was not beneficial for maintaining the undifferentiated state of the hESCs.
There are, at present, more than 30 research groups with over 300 people in total involved in stem cell research at 9 different institutes in Sweden. They are clustered around the three major sites Karolinska Institute in Stockholm, Sahlgrenska Academy in Gothenburg and Lund University in the south of Sweden.
Start-up companies have been founded around these leading stem cell research units in Stockholm and Gothenburg, in hope to reap the rewards of this fast developing area in biomedicine. Research teams closely linked to the Sahlgrenska Academy in Gothenburg and Karolinska Institute in Stockholm respectively, have formed Cellartis AB, Neuronova and OvaCell.
Cellartis AB is based in Gothenburg and was built around a large group of stem cell researchers; its scientific founders include professors Peter Eriksson, Lars Hamberger and Henrik Semb linked to the Sahlgrenska Academy.
The company operates four business areas to capture both short-and long-term businesses potential. Initially the company will generate revenue from stem and progenitor cell production, media development and creation of toxicological tests.
The company has derived hES cell lines since early 2001 and has cell lines that are eligible for use in all countries that allow hES cell research. Cellartis AB now has more than 30 hES cell lines available. Two of the cell lines are also listed on the National Institutes of Health (NIH) Human Embryonic Stem Cell Registry.
However, says Johan Hyllner, CEO of Cellartis AB "...it will take several years before we’ve learned enough to implement cell-based therapies for neurological disorders."
Another company, Neuronova, has received most of the attention. Headed by Jonas Frisén, a professor at Karolinska Institute, he was the first to discover adult stem cells in the brain, and that they had the capacity to generate new neurones and supporting cells. The discovery was heralded by the "Science" journal as the most important in 2000.
The primary focus for Neuronova’s research is in the treatment of neurological degenerative diseases, and in finding ways to promote the generation of new nerve cells. The research is directed toward developing treatments for Parkinson's, Alzheimer's, Amyotrophic Lateral Sclerosis (ALS – also known as Lou Gehrig's disease) and Multiple Sclerosis (MS).
Professor Magnus Westgren is one of the five founding members of OvaCell, a biotech start-up company located in the Stockholm region. The founding members of OvaCell all have a background in the research groups of the Karolinska Institute.
Prof. Westgren and his colleagues obtained the first ethical permit to grow human embryonic stem cells in Sweden. OvaCell also has access to 6 of the stem cell lines listed in the NIH register, thus making the company eligible for US funding for research. Research at OvaCell has been concentrated on development of cell cultivation and differentiation of stem cells into brain, heart, cartilage and insulin producing cells.
Swedish intellectual property law, which grants all rights to the researcher-inventor rather than to the research institution, is a significant incentive to entrepreneurial initiatives by researchers. If Sweden continues to have a supportive bio-ethical climate and the political establishment continues to support stem cell research as they have so far, there will be many more stem cell companies in a few years time.
References:
Human blastocysts for the development of embryonic stem cells – RBMOnline, Sept 2004
Cultures of human embryonic stem cells – RBMOnline , Sept 2004
Links:
Invest in Sweden Agency
Swedish Research Council:
Read more on Sweden’s Stem Cell Research:
Sweden's Stem Cell Success – CellNEWS, Saturday, 19 October 2002
Sweden prepares legislation for therapeutic cloning of human stem cells – CellNEWS, Saturday, 06 March 2004
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