12th edition of my human genetics textbook


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Glenn Nichols, surrounded by his hospice team. The author is in yellow.

Genetic Linkage

Human Stem Cells from Amniotic Fluid

July 4, 2012

Tags: human embryonic stem cells, induced pluripotent stem cells, transcriptome, amniotic stem cells, valproic acid

Stem cells from amniotic fluid are like Russian nesting dolls -- they are derived from the cells that would become sperm or eggs in a fetus.
A new source of human stem cells reminds me of Russian nesting dolls: They come from amniotic fluid. When exposed to a seizure drug (valproic acid), they divide to give rise to cells that can specialize as nearly any cell type – they are “pluripotent,” like embryonic stem (ES) cells. But the new stem cells are most like precursor cells in a fetus that become sperm and eggs. And so the cells derived from an organ in a pregnant woman might otherwise, if paired with the opposite type of sex cell, have become her grandchildren!

Pascale Guillot, PhD, from Imperial College London and her colleagues describe the new source of human pluripotent stem cells in the journal Molecular Therapy. They are likely safer than the human induced pluripotent stem cells that are “reprogrammed” by injection of genes that encode four key transcription factors. These “iPS” cells have dominated the field in recent years, as researchers have used them to track “diseases-in-a-dish” starting from patients’ skin fibroblasts.

Using valproic acid is simpler than reprogramming with DNA, RNA, or proteins, which is inefficient and can cause cancer. And the drug is inexpensive and FDA approved. “Valproic acid is a small molecule epigenetic modifier that relaunches transcription,” Dr. Guillot says, restoring some developmental potential to the amniotic cells. The treated cells express some genes that untreated cells don’t, indicating that the valproic acid does something. The treated cells also share 82% of their transcriptome – the set of active genes – with human ES cells. They’re unique, so far, among stem cells.

“I think this could be an exciting new player in the pluripotent stem cell field, and certainly has the potential of making a big impact on regenerative medicine – provided the somewhat controversial way of obtaining these cells can be overcome,” says Florian Siebzehnrubl, PhD, a researcher in the department of neurosurgery at the University of Florida in Gainesville. The cells come from first trimester abortion medical waste – but collecting them at amniocentesis, a few weeks later, would solve that problem.

The researchers speculate that the new stem cells will be of clinical use because they can give rise to structures from all three tissue layers of the early embryo. So far in experiments the cells yield neural tube and squamous epithelium (ectoderm), connective tissues including blood (mesoderm), and gut and lung linings (endoderm).

“One of the hurdles to overcome in regenerative medicine, either for cell-based therapies or for tissue engineering, is the limited capacity of the cells to differentiate into non-mesodermal lineages. Here, we can use these cells not only for the treatment of hematopoietic (blood) diseases, but also for pathologies affecting tissues of endodermal or ectodermal origin,” explains Dr. Guillot.

But rather than saving amniotic stem cells doused with valproic acid for individuals, the researchers envision a limited number of cell lines stored in banks from which many people can make withdrawals. The precedent lies in a simulation for hES cells. Researchers at Cambridge University calculated that 150 hES cell lines could provide cell therapies for about a third of the human population, based on HLA types (the cell surface molecules used in tissue matching). The new stem cells might also be used for drug testing and recreating diseases-in-a-dish, Dr. Guillot says.

It’s becoming difficult to keep up with the variations on the human stem cell theme. The “types” of stem cells – embryonic, iPS, adult, and now valproic-acid-treated amniotic cells – may look alike and share basic characteristics, yet they also have some different activities, fueled by different patterns of gene expression and epigenetic distinctions. As in many matters scientific, the more we learn, the more we realize we need to discover.

This blog appeared in a longer, more technical version on Scientific American blogs on July 3.

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