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Editorial: 鈥�In praise of stem-cell simplicity鈥�

BABIES with holes in their diaphragms could soon become the first humans treated with 鈥渟pare parts鈥� built from their own stem cells. The cells, taken from amniotic fluid, would be grown in the lab ready to be implanted when the baby is born.

If the trial goes ahead, it could be the start of an entirely new approach to treating congenital defects. What鈥檚 more, gene such as the one causing haemophilia could actually be treated while the baby is still inside the womb (see 鈥淕ene upgrade before birth鈥�).

Common such as Bochdalek hernia, where a hole in the diaphragm allows the stomach and intestines to protrude into the thorax, can cause lifelong breathing difficulties and are potentially fatal. At present, they are repaired with patches of Teflon, but these can detach as the baby grows, requiring repeat operations. The hope is that patches made from a baby鈥檚 own tissue will become a permanent part of the diaphragm, growing alongside it.

鈥淎 patch to cover a hole in the diaphragm could be made from the baby鈥檚 own cells before it is born鈥�

Researchers pioneering the treatment intend to apply to the US Food and Drug Administration (FDA) before the end of the year for permission to treat 20 babies soon after birth with custom-built patches.

Fetuses normally shed numerous cells into the surrounding amniotic fluid. Of these about 1 per cent are amniotic stem cells, which can be extracted by amniocentesis in the first weeks of pregnancy.

Early ultrasound tests identify fetuses in need of diaphragm repair. A patch can then be fashioned from the extracted cells during pregnancy.

Because the cells and any spare parts made from them originate with the fetus, they would hopefully not be rejected. And the only invasive procedure needed before birth would be amniocentesis. The stem cells used, called amniotic mesenchymal stem cells (aMSCs), multiply twice as fast as any other known type of stem cell, so once collected they can generate enough material to build spare tissue before the baby is born.

If the FDA grants permission, the trial would take place at the Children鈥檚 Hospital Boston, in Massachusetts, where the procedure has been developed and tested in animals over the past decade. 鈥淲e鈥檙e just waiting for the green light,鈥� says team leader . 鈥淚f approved, it will be the first trial of this strategy, and the first based on amniotic fetal stem cells,鈥� says Fauza.

Working mainly in sheep and rabbits, Fauza鈥檚 team has successfully developed tissue to repair a range of congenital defects in the diaphragm, the sternum, the chest wall, facial bones and the trachea. They have also been making identical parts from aMSCs, so that if permission for trials is given, the researchers already know how to extract, grow and fashion the requisite human parts. The FDA has already had input into the process, and the human cells are harvested, multiplied and grown according to strict safety and purity criteria.

The submission will include data from a trial in 27 sheep, comparing the performance of diaphragm patches made with and without amniotic stem cells, plus patches made from Teflon.

At the end of the 14-month trial, the equivalent for sheep of reaching adulthood, only three of nine stem cell grafts had failed, compared with five made from Teflon and all nine grafts made identically to the stem cell graft, minus the actual cells (Journal of Pediatric Surgery, ). 鈥淭he message is that having cells in the graft makes a significant difference,鈥� says Fauza.

The comparison also showed that the cell-based grafts are as good as or better than existing treatments, which should hopefully clear the way for trial approval, he says. The sheep given the grafts suffered no ill effects, and no graft in any of Fauza鈥檚 experiments has shown any sign of turning cancerous.

The grafts are made by sandwiching together a gel containing the amniotic cells with an elastic layer made from an artificial skin-like product and a porous layer made from pig intestinal tissue stripped of all cells. Such tissue is often used in hernia operations.

If the trial goes ahead and is successful, Fauza鈥檚 team plans to apply for permission to try another type of graft made from aMSCs, this time as an emergency procedure. Some babies are born with potentially fatal congenital airway blockages, where the trachea is fused, for example. Fauza and his team believe they can repair these by replacing fused trachea with tubes of tissue grown from the baby鈥檚 cells.

Other researchers in the field expressed hope that the trial would go ahead. 鈥淔auza has been doing a lot on the tissue manufacturing side, and his work is fantastic,鈥� says Anna David of University College London, who is co-leader of a team developing potential treatments for blood disorders based on amniotic fetal stem cells.

In one final development, Fauza and his colleagues have begun work that could be of medical benefit to everyone.

They have demonstrated in sheep that fetal amniotic stem cells may be one of the key factors explaining why wounds heal faster and better inside than outside the womb.

Fauza鈥檚 team applied a gauze to exclude amniotic cells from one wound but not another in the same sheep fetus, and found that the uncovered wound healed several days faster, and more thoroughly, than the masked wound inaccessible to the stem cells.

鈥淚t鈥檚 biological validation that these cells are already being used by nature to repair things, in this case, fetal wounds,鈥� says Fauza (Stem Cells and Development, ).

He says that if the human equivalent match their promised potential, it may become routine for every fetus鈥檚 amniotic stem cells to be stored and used to accelerate wound healing or make spare tissue later in life.