It is possible to take stem cells from amniotic fluid and reprogram them to a more versatile “pluripotent” state similar to embryonic stem cells and do this without inserting extra genes, according to a new study published online in the journal Molecular Therapy on 3 July.
Scientists from Imperial College London, and University College London Institute of Child Health, and colleagues, said their discovery means it may be possible to store stem cells from donated amniotic fluid for clinical and research use, offering a much needed alternative to the limited supply of embryonic stem cells.
“These cells have a wide range of potential applications in treatments and in research. We are particularly interested in exploring their use in genetic diseases diagnosed early in life or other diseases such as cerebral palsy,” said co-senior author Dr Pascale Guillot, from the Department of Surgery and Cancer at Imperial.
Stem cells hold promise for regenerative medicine because they have the potential to become virtually any cell in the body. The current “gold standard” of human stem cells is the human embryonic stem cell (hESC), which is harvested from human embryos.
However, researchers and clinicians are keen to find alternatives to hESCs because of ethical concerns about using human embryos and also because of their limited availability.
Previous studies have shown it is possible to use other types of cell and, by introducing extra genes, often using viruses as carriers, make them almost as versatile or pluripotent as hESCs. For instance, scientists have reprogrammed human skin cells to behave like embryonic stem cells.
But this way of making induced pluripotent stem cells (iPSCs) is not efficient and there is also a risk that the DNA disruption that occurs (something the authors attribute to “random integration of the reprogramming transgenes into the host genome”) will lead to tumors.
This new study is the first to make iPSCs without having to insert foreign genetic material into the cells.
Guillot and colleagues also found the iPSCs they made from amniotic fluid stem cells (AFSCs) showed some of the characteristics normally only seen in embryonic stem cells, that are not present in iPSCs made from adult cells.
Study co-senior author Dr Paolo De Coppi, from the UCL Institute of Child Health, and Great Ormond Street Hospital (GOSH), said:
“This study confirms that amniotic fluid is a good source of stem cells. The advantages of generating pluripotent cells without any genetic manipulation make them more likely to be used for therapy.”
Amniotic fluid is a nourishing liquid that surrounds the fetus in the womb. As it contains cells from the fetus, including stem cells, it is sometimes used in a test called amniocentesis to screen for genetic diseases. The test, generally done in the first three months of pregnancy, carries a 1% risk of miscarriage.
For this study, Guillot, De Coppi and colleagues used stem cells (AFSCs) recovered from amniotic fluid taken for amniocentesis where the mothers had also given permission for it to be used for other purposes.
They then cultured the cells on a gelatinous protein medium developed for growing hESCs. They also added the drug valproic acid to the medium, which reprogrammed the AFSCs to a more primitive state.
Extensive tests showed that the reprogrammed AFSCs were very similar to hESCs, for instance:
“The cells share 82% transcriptome identity with hESCs and are capable of forming embryoid bodies (EBs) in vitro and teratomas in vivo,” write the authors.
Thus even after growing in culture for some time, the reprogrammed AFSCs had the potential to grow into functioning cells of many types, including liver, bone and nerve cells. They also kept this ability even after freezing and thawing.
In summarizing their achievement, Guillot said:
“Amniotic fluid stem cells are intermediate between embryonic stem cells and adult stem cells. They have some potential to develop into different cell types but they are not pluripotent. We’ve shown that they can revert to being pluripotent just by adding a chemical reagent that modifies the configuration of the DNA so that genes that are expressed in the embryo get switched back on.”
He and his colleagues hope these findings show AFSCs have the potential to treat many diseases. Donated cells could be stored for clinical use, for research, and to screen drugs.
Previous research estimates that cells from 150 donors would provide a match for 38% of the population.
De Coppi said:
“At GOSH we have focused on building organs and tissues for the repair of congenital malformations, which are usually diagnosed during pregnancy. Finding the way of generating pluripotent cells from the fluid that surround the fetus in the womb move us one step further in the this direction.”
Funds from the Genesis Research Trust, the Henry Smith Charity and the children’s charity Action Medical Research, helped pay for the study.
Dr Caroline Johnston, Research Evaluation Manager with Action Medical Research said:
“These new findings could be a step forward for treatments of a wide range of diseases that affect babies and children.”
The children’s charity is also funding the team to investigate the therapeutic benefits of transplanting donated placental stem cells from healthy babies to babies with brittle bone disease.