Hannah Warren, Age 2-1/2, Gets a New Trachea

Meet Hannah Warren. She’s a brave 2-1/2 year old girl who is now the youngest patient to receive a new trachea coated with her own stem cells.

Hannah was born in South Korea in 2010 with the rare congenital condition called tracheal agenesis where the trachea (windpipe) is not formed. This is a fatal condition unless their is another way for air to get into the lungs, usually by an abnormal connection between the windpipe and esophagus called a tracheo-esophageal fistula .

Fortunately, Hannah did have such a fistula, and has survived by means of an plastic tube inserted through her mouth into her lungs. Because of this, Hannah has been unable to eat or drink normally or to speak. She had lived her entire life in a hospital in South Korea.

That is until recently, when she was transferred to the Children’s Hospital of Illinois. There, a surgical team lead by Dr. Paolo Macchiarini, from the Karolinska Institute in Sweden, performed a nine-hour operation which implanted an artificial trachea which had been coated with stem cells obtained from Hannah’s bone marrow.

hannah-warren-0430Hannah appears to be doing well postoperatively. Although she is still on a ventilator, physicians believe she will eventually be able to be discharged home and to live an normal life.

Her parents, Darryl and Young-Mi Warren, are ecstatic, telling People magazine:

“We feel like she’s reborn. They hope that she can do everything that a normal child can do but it’s going to take time.This is her only chance but she’s got a fantastic one and an unbelievable one.”

Dr. Macchiarini cautions that Hannah may need a new trachea as she grows, possibly in four years. The team tried to delay this replacement by using an oversized  implant and by using some biodegradable plastic in the scaffolding which may allow it to stretch over time.

Tracheal Agenesis and Tracheo-esophageal Fistulas

Tracheal agenesis (TA) is a rare condition diagnosed shortly after birth in which the breathing tube (trachea) between the voicebox (larynx) and the bronchial tree in the lungs is missing. The windpipe may be completely missing (agenesis), or present but malformed (atresia).


TA occurs in about 1 in 50,000 births. It is more common in boys than girls. It can be associated  with a premature birth  and with a condition called polyhydramnios , where there is too much amniotic fluid. Other birth defects can be seen in 90% of cases, especially those affecting the cardiovascular or gastro-intestinal systems and the genito-urinary tract.

Since there is no direct connection between the lungs and the air, infants with this problem have the following symptoms:

  • Trouble breathing
  • Blue coloration to the skin, mouth or extremities
  • No cry is heard
  • A history of polyhydramnios
  • If a physician tries to put a breathing tube in the baby (intubation) the attempt is unsuccessful

The diagnosis is confirmed by CT scan.Tracheoesophageal_Fistula_Types

The condition is considered fatal unless there is also another birth defect called a  tracheo-esophageal fistula (TEF). A TEF is an abnormal connection between the feeding tube (esophagus) and the windpipe.  This can happen in a number of configurations (see figure, right). It is more commonly associated with esophageal atresia (where it is the esophagus that is interrupted).


The Tracheal Implant

The tracheal implant inserted into little Hannah consists of a scaffold manufactured from small fibers of a special polymer.

In older patients on which the procedure has been performed (11 to date) this material does not degrade. As mentioned above, because of Hannah’s age, some biodegradable polymers were added to her implant in the hope that it would be more flexible and allow for growth. The polymer is also biocompatible, meaning that it does not provoke an reaction from the immune system.

The stems cells are then collected. Stem cells are special cells that are can differentiate into all the different kinds of specialized cells in the body. They are also important in maintaining  the normal turnover of dead cells in organs that regenerate, such as the blood, skin, or the  intestinal tissues. Stem cells can be obtained retrieving bone marrow by putting a special needle in the in the hip bone. The bone marrow is centrifuged and the stem cells separated from the other bone marrow components.

Bioreactor_principle.svgThe scaffold is then place in a “bioreactor” (which Dr. Macchiarini likens to a “shoe box”)  with stem cells obtained from the patient. This scaffold attracts the stem cells and allows them to attach to it.  When the implant is placed into the body, the cells are still pluripotent  (meaning they are undifferentiated- just like stem cells ). The human body then takes over as the bioreactor, instructing it to differentiate into trachea cells.

Endoscopy, a procedure where a tube with a camera is put into the trachea,  has been done on patients after the surgery and researchers have found cells that have become tracheal cells in one week’s time. A full transformation has been found in 2 to 3 weeks!

Hannah’s physician, Dr. Paolo Macchiarini (right) says he was drawn to regenerative medicine because he “was frustrated that the windpipe was one of the very few organs that we are unable to transplant, because it does not have a distinct blood vessel supplying it. ”

He told Future Medicine that this process has been in international collaboration: Scientists at the Karolinska Institute in Sweden worked with scientists in London, who designed the scaffold, and groups in the USA and Germany, who produced the specific bioreactor to seed the scaffold.

Asked about the future of this procedure for transplantation of other organs, Dr. Macchiarini said we could most likely produce heart valve or blood vessels, but that we are not yet ready for more complex organs such as hearts or lungs.

Dr. Macchiarini would like to begin clinical trials in the United States if they could gain FDA approval.

There is an interesting interview of Dr. Macchiarini for NPR’s Science Friday. You can listen to it by clicking here.

Do you think this the wave of the future for transplant medicine?

Michele R. Berman, M.D. was Clinical Director of The Pediatric Center, a private practice on Capitol Hill in Washington, D.C. from 1988-2000, and was named Outstanding Washington Physician by Washingtonian Magazine in 1999. She was a medical internet pioneer having established one of the first medical practice websites in 1997. Dr. Berman also authored a monthly column for Washington Parent Magazine.

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