|Karl Tryggvason (left)|
and Outi Hovatta
Currently the use of human embryonic stem cells is highly controversial as they are made from surplus in vitro fertilized (IVF) embryos that are not used for the generation of pregnancies. The embryos are destroyed in the process. Therefore it has been illegal in the USA to to use this method for deriving embryonic stem cell lines. Sweden s legislation has been more permissive. It has been possible to generate embryonic stem cells from excess, early IVF embryos with the permission of the persons donating their eggs and sperm.
Now, an international research team led by Karl Tryggvason, Professor of Medical Chemistry at Karolinska Institutet and Professor at Duke-NUS Graduate Medical School in Singapore has, together with Professor Outi Hovatta at Karolinska Institutet, developed a method that makes it possible to use a single cell from an embryo of eight cells. This embryo can then be re-frozen and, theoretically, be placed in a woman's uterus. The method is already used in Pre-implantation Genetic Diagnosis (PGD) analyses, where a genetic test is carried out on a single cell of an IVF embryo in order to detect potential hereditary diseases. If mutations are are not detected, the embryo is inserted in the woman's uterus, where it can grow into a healthy child.
"We know that an embryo can survive the removal of a single cell. This makes a great ethical difference." said Karl Tryggvason.
The single stem cell is then cultivated on a bed of a human laminin protein known as LN-521 that is normally associated with pluripotent stem cells in the embryo. This allows the stem cell to duplicate and multiply without being contaminated. Previously the cultivation of stem cells has been done on proteins from animals or on human cells, which have contaminated the stem cells through uninhibited production of thousands of proteins.
"We can cultivate the stem cells in a chemically defined, clinical quality environment. This means that one can produce stem cells on a large scale, with the precision required for pharmaceutical production." said Karl Tryggvason.
Embryonic stem cells are pluripotent and can develop into any kind of cell. This means that they can become dopamine producing cells, insulin producing cells, heart muscle cells or eye cells, to name but a few of the hopes placed on cell therapy using stem cells.
"Using this technology the supply of human embryonic stem cells is no longer a problem. It will be possible to establish a bank where stem cells can be matched by tissue type, which is important for avoiding transplants being rejected." said Karl Tryggvason.
The research was funded by the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Söderberg Foundation, AFA Insurance, the Sigrid Juselius Foundation, the EU's Seventh Framework Programme and the Singapore National Medical Research Council. LN-521 has been developed by the Division of Matrix Biology at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet and is currently marketed by the biotechnology company BioLamina, founded by Karl Tryggvason.
- Sergey Rodin, Liselotte Antonsson, Colin Niaudet, Oscar E. Simonson, Elina Salmela, Emil M. Hansson, Anna Domogatskaya, Zhijie Xiao, Pauliina Damdimopoulou, Mona Sheikhi, José Inzunza, Ann-Sofie Nilsson, Duncan Baker, Raoul Kuiper, Yi Sun, Elisabeth Blen (2013). Clonal culturing of human embryonic stem cells on laminin-521/E-cadherin matrix in defined and xeno-free environment. Nature Communications DOI: 10.1038/ncomms4195