Delivered through amniotic fluid, stem cells could treat a range of birth defects

Transamniotic stem cell therapy, or TRASCET, is like amniocentesis is reverse.
Amniotic fluid is routinely withdrawn for prenatal testing. It could also be a delivery route for fetal cell therapy to treat congenital anomalies, with broader applications than once thought.

The amniotic fluid surrounding babies in the womb contains fetal mesenchymal stem cells (MSCs) that can differentiate into many cell types and tissues. More than a decade ago, Dario Fauza, MD, PhD, a surgeon and researcher at Boston Children’s Hospital, proposed using these cells therapeutically. His lab has been exploring these cells’ healing properties ever since.

Replicated in great quantity in the lab and then reinfused into the amniotic fluid in animal models — a reverse amniocentesis if you will — MSCs derived from amniotic fluid have been shown to repair or mitigate congenital defects before birth. In spina bifida, they have induced skin to grow over the exposed spinal cord; in gastroschisis, they have reduced damage to the exposed bowel. Fauza calls this approach Trans-Amniotic Stem Cell Therapy, or TRASCET.

New research findings, reported this month in the Journal of Pediatric Surgery, could expand TRASCET’s therapeutic potential.

Spina bifida (left) and gastroschisis were among the first TRASCET applications studied.
Spina bifida (left) and gastroschisis

From your womb to your baby’s marrow

The beauty of the TRASCET approach, slowly but steadily moving toward clinical testing, is that the healing cells are the baby’s own. TRASCET simply returns them to their original environment, in more concentrated amounts. “It appears that we are basically amplifying a process that already takes place in nature,” says Fauza.

Hester Shieh, MD, a surgical research fellow in Fauza’s lab, conducted a study that injected amniotic-fluid MSCs (afMSCs) into fetal animals, then comprehensively screened the fetus to see where the cells landed. To the team’s surprise, large numbers turned up in the fetal bone marrow.

“No one had ever described a communication between the amniotic fluid and the fetal circulation,” says Fauza. “That is not currently taught in medical school.”

Stem cells delivered via TRASCET have been shown to engraft in the fetal bone marrow.

But more practically, the research suggests that afMSCs can treat a wider variety of congenital defects than originally thought, since ordinary MSCs from the bone marrow are already known to be active in tissue repair throughout the body.

“We had initially studied spina bifida and gastroschisis because these defects are exposed directly to the amniotic fluid,” explains Fauza. “At first, we thought the cells worked because they landed on the damaged area and seeded directly on the defect.

“But from the bone marrow, these cells can reach essentially any part of the body,” he continues. “If we have congenital abnormalities that aren’t exposed — such as pulmonary hypoplasia, kidney malformations or non-structural diseases such as blood disorders — you could potentially access them through a simple amniotic injection. This is something we are now beginning to study.”

Amniotic injections for congenital defects?

The team is now investigating TRASCET in animal models of congenital diaphragmatic hernia, a hole in the diaphragm that allows abdominal organs to press into the chest cavity, as well as VACTERL association, a genetic condition causing multiple anomalies. (VACTERL stands for Vertebral defects, Anal atresia, Cardiac defects, Tracheo-esophageal fistula, Renal anomalies and Limb abnormalities.) The researchers can then examine where the afMSCs engraft after they’re injected into the womb and their ability to repair the different defects.

In the meantime, Fauza is preparing to submit a pre-IND request to the Food and Drug Administration for a clinical trial using TRASCET to treat gastroschisis prenatally. The FDA will then either recommend to proceed with a formal IND submission or ask the team to collect more laboratory data.

Fauza’s work has inspired other scientific groups to begin looking at homing of afMSCs. So far, they seem to be confirming his findings.

And, because blood stem cells are closely related to MSCs, Fauza speculates that they, too, could also potentially be administered prenatally through the amniotic route.

“If so, we could also start treating certain fetal blood diseases through a simple amniotic injection,” he says.

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Shieh, the paper’s first author, was supported by a Joshua Ryan Rappaport Fellowship from the Department of Surgery at Boston Children’s Hospital. The research itself was supported by the Kevin and Kate McCarey Fund for Surgical Research. Co-authors on the paper were Azra Ahmed, BS, Sarah Tracy, MD and David Zurakowski, PhD, also of Boston Children’s Hospital.