Angela Irizarry is four-years old and was born with a congenital heart condition called Hypoplastic Left Heart Syndrome (HLHS). HLHS causes the main pumping chamber of the heart, the left ventricle to be abnormally small and stunted. Therefore, the heart only has one pumping chamber, and such a condition is potentially fatal.
HLHS affects approximately 3,000 babies in the US alone each year. Since babies with HLHS have an underdeveloped left side of the heart, the right side of the heart must pump blood to both the lungs and the rest of the body. Before the baby is born, the lungs are not being used because the placenta provides the oxygen for the baby and the baby is surrounded by amniotic fluid. Therefore, the lungs are bypassed by a connection between the vessels that extend from the right side of the heart to the lungs and the vessel that extends from the left side of the heart. This bypass is called the “ductus arteriosus.” The ductus arteriosus and a hole is the septum that separates the left and right side of the heart close very soon after birth (1-2 days after birth). In some children, the ductus arteriosus does not close, which is called patent ductus arteriosus (PDA). Once the ductus arteriosus closes in children who have HLHS, the right side of the heart can’t pump blood out to the rest of the body. The undeveloped heart cannot pump efficiently enough to support the life of the child, and the baby becomes very sick and may die within the first days of life.
Without two heart chambers pumping blood throughout the entire body, HLHS babies can’t deliver sufficient levels of oxygen to their organs and extremities. This severely affects their development and also causes them to turn blue and suffer from a lack of energy. According to Dr. Breuer, without a surgical repair, 70% of them die before their first birthday.
Surgical treatment of HLHS occurs in three stages. The first stage is the Norwood procedure, which is done during the first week of life. The Norwood procedure reconstructs the aortic arch, which is the main blood vessel that supplies blood to the body. Surgeons also insert a tube to connect the aorta to the blood vessel that supplies the lungs (the pulmonary artery). This shunt allows the right side of the heart to pump blood into the aorta.
The second stage is performed when the baby is 4-6 months old and is called the bidirectional Glenn procedure or hemi-Fontan. In this surgery, some of the veins that carry blood from the body are connected to blood vessels that carry blood to the lungs. This allows most of the blood to flow directly from the body into the lungs, and reduces the workload of the right side of the heart. Because blood with higher levels of oxygen is pumped into the aorta, it supplies the rest of the body with oxygen-rich blood.
The third stage is carried out when the child is 18-48 months old, and is known as the Fontan procedure. The Fontan procedure takes the remaining blood vessels that carry blood from the body and connects them to the blood vessels that carry blood to the lungs. This ensures that ALL the blood returning from the body receives oxygen in the lungs and also ends the mixing of oxygen-rich blood with oxygen-poor blood. This operation improves the general health of the child and also prevents from having the blue look.
These surgeries are traumatic, and expensive. Not all children survive them. Is there a better way? In Angela’s case, physicians have used stem cells to help Angela grow a new blood vessel in her body. This experimental treatment could rapidly advance the burgeoning field of regenerative medicine.
In August of 2011, Doctors at Yale University implanted a bioabsorbable tube into Angela’s chest. This tube is designed to dissolve over time, but before the implantation procedure, the tube was seeded with stem cells and other cell types that had been harvested from Angela’s bone marrow. Doctors are quite confident that the tube has disappeared, but in its place, a new blood vessel was built from the bones of the bioabsorbable tube. Apparently, this tube functions like a normal blood vessel.
Christopher Breuer, the Yale pediatric surgeon who led the 12-hour procedure to implant the device, commented, “We’re making a blood vessel where there wasn’t one. We’re inducing regeneration.” Before the procedure, Angela had little energy or endurance. Now, even though she is on several medications, she has the spunk of a regular child her age. Dr. Breuer and her parents are confident that she will be able to start school in the fall.
Recent advances in stem-cell science, regenerative medicine, and tissue engineering suggest that regenerative forces in our bodies that are lost soon after birth might be reawakened with strategically implanted stem cells and other tissue. This hope is fueling research at many academic laboratories and dozens of start-up companies. At these laboratories, scientists are racing to find effective ways to treat previously intractable maladies including paralysis due to spinal cord injuries, poor-functioning kidneys and bladders, and heart muscle damaged from heart attacks.
Also, regenerative medicine seeks to improve presently available treatments. For example, in the case of the Fontan procedure, pediatric surgeons implanting a synthetic blood vessel made of Gore-Tex in order to reroute blood from the lower extremities directly to the lungs instead of through the heart. While this works, this device prone to causing blood clots, infection and in some cases, the child needs additional surgeries later in life to increase the size of the blood vessels to accommodate the growth of the child. Dr. Breuer wants to create a natural conduit for blood that reduces the complications associated with a synthetic tube and grows with the child.
Though not involved in this study, Robert Langer, a researcher at Massachusetts Institute of Technology and a regenerative-medicine pioneer, called Angela’s case a “real milestone and broadly important for the field of tissue engineering.” Langer also added, “It gives you hope that when you combine cells with a scaffold and [put] them in the body, they will do the right thing.”
According to Claudia, Angela’s mother, the heart defect was diagnosed when she (Claudia) was five months pregnant. Angela had her first operation when she was 5 days old, and the second when she was 8-months old. However, she heart defect still sapped her energy and stunted her growth. Angela was shy, small for her age and lacked the stamina of a normal 3-year-old. According the Claudia, “If she ran from [the living room] to the kitchen, she got tired and she had purple lips.”
Dr. Breuer and other Yale staff met with Angela and her family four times. They discussed the advantages and risks associated with conventional synthetic tubes versus this new, bioengineered approach. Dr. Breuer said that a tissue-engineered blood vessels can still narrow or become blocked and other complications might also arise (e.g., cancer, immune system troubles etc.) that are difficult to foresee. According to Claudia Irizarry, who works as a church secretary, the family’s faith in God and their doctors influenced them to choose the bioengineered version over the synthetic version.
To say the least they are glad they did. According to Angela’s father, Angel Irizarry, who works as a carpenter, his daughter seems more like a regular kid, according to her. “It’s a huge difference,” he says. “It’s like going from a four-cylinder to an eight-cylinder car in one operation.” Before the surgery, he added, “her eyes weren’t as happy as [they are] now.”
It took Dr. Breuer four years of tedious work after he joined Yale in 2003 to develop his bioengineered blood vessel. After those four years, he sought approval from the U.S. Food and Drug Administration in 2007 to test his approach on patients. It took another four years and 3,000 pages of data before the agency allowed him to conduct his first human trials. Breuer’s clinical trial builds on the cases of 25 children and young adults who were successfully treated in Japan a decade ago with a similar approach. Dr. Breuer hopes to implant his tissue-engineered blood vessel into a second patient soon as part of a six-patient Phase I/II clinical trial that examines the safety of the procedure and determine if the blood vessels actually grow as the child gets grows. Breuer hopes that treatment in these patients is non-problematic. If so, then it might qualify for special FDA humanitarian device exemption.