Amniotic Stem Cells Are Used With Biomaterials to Fabricate Functional New Heart Valves

When children are born with abnormally formed heart valves, their prognosis is poor and surgery is the only option. What if we could fix the heart valves before the baby is ever born? “Science fiction,” you say. Fortunately fetal surgery, the use of surgical treatment on an unborn baby afflicted with certain life-threatening congenital abnormalities, is a procedure that has been used for decades, and the technology to do these procedures is always improving. Fetal surgery attempts to correct problems that are too severe to correct after the baby is born.

There are two main techniques used in fetal surgery. Open fetal surgery used a Cesarean section (hysterotomy) to expose the portion of the baby that requires surgery. After completion of the surgery, the baby is returned to the uterus and the uterus is closed. Sometimes the surgery is scheduled to coincide with the delivery date, and surgery is done before the cord is cut. This way, the baby is sustained by the mother’s placenta and doesn’t need to breathe on his own.

If the baby’s airway it blocked, a procedure called EXIT (ex utero intrapartum treatment) is used. During EXIT procedures, an opening is made in the middle of the anesthetized mother’s belly. The baby is partially delivered through the opening but remains attached by the umbilical cord. Now the surgeon clears the airway so the fetus can breathe. After the procedure, the umbilical cord is cut and clamped, and the infant is fully delivered. EXIT is used to give the surgeon time to perform multiple procedures to clear the baby’s airway, so that once the umbilical cord is cut, the baby can breathe with an unblocked airway.

Fetoscopic surgery makes use of fiber-optic telescopes and specially designed instruments to enter the uterus through small surgical openings to correct congenital malformations without major incisions or removing the fetus from the womb. Fetoscopic surgery is less traumatic and reduces the chances of preterm labor.

Now that we have some clue about fetal surgery, how do we use this to fix heart valves? To fix heart valves, we must replace them with something else. The best alternative would be to grow new heart valves, but these do not grow on trees. What then should we do? The answer is, construct new ones from stem cells.

Tissue engineering uses organic polymers that can be molded into the shape of particular organs and seeded with cells. These polymers are nontoxic and biodegradable. Therefore, once they are seeded with cells, the cells will degrade the polymers and replace them, and grow into the shape originally established by the mold. A special class of fetal stem cells called amniotic fluid stem cells have proven to be especially good at making heart valves and a recent publication shows the feasibility of using laboratory-fashioned heart valves as replacements in fetal sheep.

Weber and colleagues from the Swiss Center for Regenerative Medicine and Clinic for Cardiovascular Surgery, University Hospital Zurich, used stem cells from amniotic fluid to fashion new heart valves. Amniotic fluid comes from a sac that surrounds the embryo and the fetus and is filled with fluid. The embryo and then fetus is suspended in this fluid and the membrane is called the amnion and the fluid is called amniotic fluid.

The Swiss group isolated amniotic fluid cells (AFCs) from pregnant sheep between 122 and 128 days of gestation by means of a technique called “transuterine sonographic sampling.” This technique is rather precise and does not represent a severe risk to the fetus. They then made stented, three-leafed heart valves from a scaffold made from a biodegradable polymer called PGA-P4HB, which stands for poly-glycolic acid dipped in about 1% poly-4-hydroxybutyrate. This material formed a composite matrix that was used to form a heart valve-shaped mold that was then seeded with AFCs. The AFCs grew into the mold, degraded the polymer matrix and assumed the shape of the mold (Weber B., et al., Biomaterials. 2012 Mar 13).

These fabricated heart valves with then implanted into their natural position by means of an in-utero closed-heart hybrid approach. Other sheep fetuses had heart valves implanted that were not seeded with AFCs as a control. 77.8% of the animals implanted with AFC-seeded heart valves survived. Heart functionality tests were measured with echocardiography and angiography, and 1 week after implantation, the fabricated heart valves were completely functional and showed structural integrity (they weren’t falling apart), and also showed no signs of blood clots forming on them (which occurs when heart valves have structural imperfections that allow clotting proteins to stick to them and form clots).

While this experiment represents an interesting approach for fixing fetal hearts, it is still in the experimental stages. Nevertheless, this provides the experimental basis for future human fetal prenatal heart treatments that use completely biodegradable materials seeded with a baby’s own stem cells to make a replacement tissue.