In a Tissue-Engineering First, Doctors Think the Boy's New Windpipe Could Grow
By Brenda Goodman, MA
WebMD Health News
July 25, 2012 -- Ciaran Finn-Lynch is an accidental medical pioneer. With his life in danger, doctors used the 13-year-old's own stem cells to grow him a new windpipe, and they did it inside his body -- a feat that's never been accomplished before.
"It's a really heroic story," says Harald C. Ott, MD, an instructor of medicine at Harvard Medical School in Boston. "They really saved this kid's life."
Ott worked out some of the science that made the procedure possible but was not directly involved in Ciaran's treatment.
Two years after the surgery, doctors say Ciaran (pronounced KEER-an) is living the life of a normal teen. He's grown more than 4 inches and gone back to school. Best of all, he has no need for an expensive and complicated regimen of anti-rejection drugs.
What doctors are learning from his case could help thousands of children born each year with life-threatening birth defects.
An Urgent Medical Need Drives a Discovery
Ciaran was born with a windpipe so small and deformed that it caused his lungs to collapse.
Doctors managed to hold his airway open using metal tubes. But eventually the tubes eroded into his aorta, the large vessel that carries blood out of the heart. He was rushed to the hospital with massive bleeding. Twice.
The second time, the bleeding stopped on its own. That gave his doctors a small window of time to look for other options.
Two years earlier, scientists had devised a new way to create organs using a patient's own stem cells. Though the technique had only been tried in adults, they thought the same method might work for Ciaran.
Working quickly, his doctors located a trachea, or windpipe, removed from a 30-year-old Italian woman whose organs were donated after she died. The trachea was about the same size and shape needed to replace the deformed one that Ciaran was born with.
Scientists in Italy cleaned the organ of all its cells using a method discovered at Harvard Medical School. Working with a detergent found in shampoo, they were able to strip the cells away from the protein scaffold they grew on. It's a bit like remodeling a house by first tearing it down to the studs.
That step was important because it cleared away any markers that might have caused Ciaran's immune system to reject the transplant.
Back at Great Ormond Street Hospital, a children's hospital in London, doctors removed stem cells from Ciaran's bone marrow. Stem cells are uniquely flexible cells that can be coaxed to grow into nearly any kind of tissue. The cells were sent to a specialized lab to be purified and returned to the hospital the same day.
After surgeons sewed the stripped-down donor windpipe in Ciaran's chest, they coated it with his purified stem cells. They also injected the tissue scaffold with proteins that encourage cell growth. For good measure, they took tissue samples from Ciaran's own trachea and placed those inside the tube of the windpipe with the stem cells. The tissue samples acted like blueprints, giving the stem cells instructions for what they should become.
The 'Holy Grail' of Tissue Engineering: Organs That Grow
Ciaran's case, which is reported in The Lancet, is the first time doctors have rebuilt an organ inside the body. Normally, donor organs are washed, reseeded with stem cells, and then grown in a lab until they are ready to be used in a patient. The process takes several weeks.
"We did not have the time to engineer and to culture the cells in a bioreactor because this child needed to have something done quickly. We used the child, himself, as a bioreactor," says researcher Paolo De Coppi, MD, PhD, one of the surgeons who treated Ciaran. "For him, there was no other option."
Worldwide, just 12 tissue-engineered tracheas have been transplanted into patients. Ciaran is the first child to get one. Doctors are watching him closely to see if the new trachea will keep up with his growth spurts. Since he's already shot up more than four inches since the operation, doctors think there's a good chance it will.
"We believe the matrix of the transplant will remodel with time. So it should allow, when the child grows, for the transplant to grow with the child," De Coppi says.
About 3% of babies are born with organs or tissues that are so malformed they threaten the child's life or growth. About 2% of newborns have poorly developed windpipes or lungs.
If tissue-engineered grafts like the one Ciaran has could grow, doctors think the damaged parts could be replaced almost as soon as they're discovered.
"A lot of kids, like kids with heart defects, any sort of structural defect that needs repair, if you do a repair with something that doesn't grow with the patient, you're committing them to a series of operations," Ott tells WebMD.
"So the holy grail of tissue engineering is to come up with something that is so integrated into the human body that it grows with the human body," he says. "That would make a big difference."
Michele Bachmann is the owner of Grapes 2 Glass Wine Boutique, 10351 Washington Ave., Suite 200, in Sturtevant. Bachmann has overcome a very aggressive form of cancer, thanks in large part to a stem cell transplant. She initially was given 18 months to live, or until she’d need another transplant. She’s had neither and is still in remission six years later. In the past, the average survival for her type of cancer has been two to three years.
RACINE COUNTY — After more than four decades, Michele Bachmann knew her body well enough to know there was something definitely wrong.
Yet it would be almost a year of frustration, aggravation and suffering before her feelings would receive validation — ultimately landing her in a grueling fight to save her life.
“I kept saying I was sick. People thought I was crazy,” she said. “I just kind of felt off, tired. Things just weren’t right.”
Bachmann, 50, who lives in Racine, said she contacted the doctor, who ran some blood tests.
“He said everything was fine. He said I just need to lose some weight and sit at my desk properly,” Bachmann said, giving her head a slight shake.
It wasn’t until later that she learned those tests results showed something more: Her white blood cell count was high.
“He said ‘oh no, you need to exercise, lose weight, take vitamins,’ ” she said. “By the time I got diagnosed in August, my spleen was the size of a basketball and weighed 25 pounds.”
It was about 11 months from the time she first knew she was sick before Bachmann — who owns Grapes 2 Glass Wine Boutique, at 10351 Washington Ave., Suite 200, in Sturtevant — received the proper diagnosis. It just wasn’t the one anyone wanted to hear.
She was in so much pain one day that she couldn’t make it to work in North Chicago, Ill., where she was a wine consultant. Her doctor was on vacation, so she went into prompt care. They took some blood, and she went home to make lunch, she said. They called her to come back because she was so low on blood. She received a transfusion, requiring three or four units, she said.
While at the hospital with her husband, parents and a friend, a doctor walked into her room, Bachmann recalled as if he stepped through that door only yesterday.
“He said ‘we just got the test results. You have leukemia,’ ” she recounted. “Everyone was in hysterics. It was a relief to me. I knew I was sick.”
He performed her first bone marrow biopsy while she still was in Wheaton Franciscan-All Saints hospital, 3801 Spring St., she said.
“It was probably one of the most horrible things I’ve ever done,” Bachmann said. “I was holding onto the railing of the bed and I probably could have broken the railing.”
But the doctor there wasn’t familiar with the type of cancer she had, Bachmann said.
Bachmann, who has nine siblings, said she called her sister, who had just completed a three-month course of chemotherapy at Froedtert Hospital in Wauwautosa because of tumors along her spinal column.
Her sister’s doctor recommended a new doctor at Froedtert, Timothy Fenske, Bachmann said. Fenske, a medical oncologist at Froedtert & The Medical College of Wisconsin, said he started working at the hospital in July 2005, and met Bachmann the following month.
He said she had mantle cell lymphoma. It is a type of non-Hodgkin’s lymphoma, he said.
“She had a lot of disease in her system,” Fenske said.
So she had a choice — the first of multiple tough decisions.
“They said where you’re at, you’ve got about two weeks to live. They explained my cancer is mainly in older men,” Bachmann said. “They said it’s only 4 percent of the types of leukemias and lymphomas. (Fenske) said ‘we could make you comfortable, or we could have you try this clinical going on right now.’ ”
But the course of treatment would be very strong.
“I said ‘if I’m gonna die in two weeks, what does it matter?’ ” Bachmann said.
She began her first chemo treatment in August 2005, and it truly was brutal, she explained. She developed sores inside her mouth. She lost her hair. She repeatedly lost her lunch. She became so weak she barely could move, she recalled.
Fenske said because Bachmann was so strong and young, and had such an extensive family support network, he suggested she undergo this type of high-dose chemotherapy. The average age of patients with Bachmann’s type of lymphoma is 63, he said.
“I thought chemo was chemo,” said Michele’s husband, Steve Bachmann. “Apparently there are hundreds of types.”
Looking back, Michele Bachmann can laugh at one type of chemo. She said the warning that came with it basically stated if she was allergic to eating rats, she might have a problem with it.
“I said, ‘well, I’ve never eaten rats, so we should be OK,’ ” she laughed.
“She’s one of our favorites,” Fenske said of Bachmann, in part because of her sense of humor. “Some people are a real challenge to get through chemotherapy. She was a trouper through it. Some people are really high maintenance.”
Often during chemo, patients’ sense of taste will be affected.
“Her thing was pickles,” Fenske said with a laugh. “She’d have this huge jar of pickles (when she came for chemo). I don’t know how many she’d work through.”
He said he suggested this type of aggressive chemotherapy because he wanted to send Bachmann’s cancer into remission, then dose her with stem cells he would transplant into her.
Stem cells are found throughout the body, including in bone marrow. Stem cells are a very basic building-block type of cells. In stem cell transplants, a batch of healthy cells is inserted into the body.
Froedtert spokeswoman Nalissa Wienke said “stem cell transplants are often the last best hope for patients.”
To help Bachmann’s body rebuild, Fenske gave her another choice, Bachmann said. She could use her own stem cells, or receive a transplant from a donor — such as one of her siblings. She chose her own stem cells, receiving the transplant Feb. 15, 2006.
Fenske said there are pros and cons to using one’s own stem cells and to using a donor’s.
Using one’s own stem cells allows doctors to administer high-dose chemotherapy, which works better at treating this type of cancer, but can leave patients without functioning bone marrows, Fenske said.
Transplanting the patient’s own stem cells also allows patients to recover better from this more aggressive, high-dose chemotherapy, Fenske explained. And it carries less of a risk — just 1 percent to 2 percent — of infection or a serious complication, he added.
So in Bachmann’s case, “it’s her own immune system coming back,” Fenske said.
But when a donor’s stem cells are used, patients would have to take anti-rejection drugs. And, they have more risk of infection, Fenske explained, at 15 percent to 20 percent.
“Historically, (with) the type of lymphoma she had, the average person only lived two to three years after diagnosis. In recent years, the prognosis has increased dramatically,” Fenske said.
Now, 50 to 60 percent of patients who receive high-dose chemotherapy and their own stem cells still are in remission six years later, Fenske said — just as Bachmann is.
An 8- to 10-year period is considered a good length of remission, Fenske said. And if it returns, he said Bachmann still could have a stem cell transplant from a donor.
“I’m just extremely, extremely happy” to be cancer-free for the past six years, she said. “I feel good.”
During the first couple of years after chemo and the transplant, she said she was waiting for the cancer to come back, almost preparing for it.
“(Now) if I feel run down, I know I didn’t go to bed early enough. I don’t have that really crappy feeling anymore,” Bachmann said. “Now I’ve got two birthdays. One in April and one on Feb. 15 — that’s my new life.”
Madeleine Connor, 2, underwent an experimental procedure using her own cord blood stem cells to repair damaged tissue in her ear and restore her hearing. (Courtesy Stephanie Connor)
A virus infection
Stephanie Connor acquired during pregnancy put her unborn daughter at significant risk for brain damage and lifelong hearing loss.
"It was traumatic," said Connor, of LaBelle, Fl, after learning about her daughter's condition. "It was like mourning the loss of a child."
At age 1, baby Madeleine was completely deaf in her right ear and her hearing was severely lost in the left, said Connor. While a hearing aid helped to amplify some sounds for Madeleine, it would never fully repair the damage in her ear.
But a simple experimental procedure that Connor enrolled in for Madeleine may have restored her hearing and reversed her condition.
In January 2012, Madeleine, 2, became the first child to undergo an experimental hearing loss treatment through an FDA-approved trial
at Memorial Hermann-Texas Medical Center that infused stem cells from her own banked cord blood into her damaged inner ear.
Within the last six months, Connor says she's seen a dramatic improvement in Madeleine's ability to hear.
"Before, when she would hear something she would look all around," Connor said. "But now we notice that she turns in the right direction of the sound."
Madeleine was also able to speak for the first time, Connor said.
For more than two decades, umbilical cord blood transplantation -- either by a baby's own cord blood or another's, depending on the type of procedure -- has been used to treat otherwise fatal diseases including blood disorders, immune diseases, and some types of cancers.
Infusing cord blood stem cells into the body may also have the potential to heal and regenerate damaged cells and tissues.
Regenerative therapy using cord blood stem cells is currently being studied as therapies to treat conditions including cerebral palsy and brain injury.
For the first time, doctors are experimenting with cord blood stem cells to regenerate hearing in children who have suffered hearing loss.
This yearlong study will follow 10 children, including Madeleine, ages 6 weeks to 18 months, who have acquired hearing loss and who have banked their cord blood with the Cord Blood Registry.
"There are a number of treatments for hearing loss, but most of them rely on amplification of noises, not reversal of the hearing loss," said Dr. Samer Fakhri, associate professor and program director in the Department of Otorhinolaryngology at Memorial Hermann-Texas Medical Center, and principal investigator of the study.
Since Madeleine is part of a study that is currently under way, it's unclear whether Connor's perceived improvement of Madeleine is really due to the stem cell procedure.
Madeleine has already had one follow-up appointment to test her speech and language development, which are indicators that her hearing has improved. She will have another one mid-July.
Fakhri said it's still too early to determine whether the procedure benefitted Madeleine, or may be beneficial for other children.
"If there's any improvement, it should be detected within six months to a year," Fakhri said. "We can't determine from just one child if there's an overall benefit."
If the study results show significant improvement overall among the collective children studied, children with acquired -- not genetic -- hearing loss, may be able to benefit from the procedure.
"We do not recommend that stem cells at this point now should be a treatment modality for hearing loss," Fakhri said.
Previous studies in mice suggest long-term hearing repair after stem cell infusion. Fakhri says it's likely that if the procedure works, children like Madeleine will have long-term restored hearing.
"The way the stem cells work is they support repair," said Fakhri. "Once you repair the damage, there's no suggestion that it will dwindle over time."
Connor said the improvement she has seen so far is enough that she is grateful that she enrolled in the trial, and she hopes the study will prove to be beneficial in repairing hearing loss so other children can be treated successfully.
"As a mom of special needs, if you're able to help a child it's huge," she said. "There's nothing that can compare to giving a child back something that's been taken away."
LABELLE, Fla.- Two-year old Madeline Conner was born with the inability to hear. But new advances in medical science could offer hope in the form of a stem cell research study.
"I really wanted her in it. It was our one shot," said her mother, Stephanie Conner.
Conner heard about a new FDA-approved stem cell study for hearing loss. She knew right away her little girl was the perfect candidate.
"It's a group of ten kids and she's the first one and the only one so far," she said.
The trial is a collaboration between Children's Memorial Hermann Hospital in Houston and the California-based Cord Blood Registry.
"This is the first study FDA regulated looking at the safety and benefit of cord blood stem cells for treatment of acquired sensorineural hearing loss. Which is loss that has to do with the damage of the inner ear and nerve fibers that go to the brain," said Principal Investigator, Dr. Fakhri.
Stem cells, saved from Madeline's own umbilical cord, were injected into her arm.
"We expect that it will be safe. You are using your own blood stem cells as if it was your own transfusion," stated Dr. Fakhri.
"It was actually a one-time treatment, just one infusion. Then we keep going, We go four times total, just so they can check her and compare all the testing they did before hand to see if there has been any improvement," said her mom.
In theory, the treatment will adjust Madeline's immune system and will help her body repair itself. In reality, researchers say they have no idea if it will work.
"We've definitely seen a lot of improvement. It's hard to say if it's 100 percent because of this or that. It's just our observation," said Madeline's parents.
"We can not expect what the results will be, but potentially it can repair and restore normal hearing," Fakhri said.
Expensive stem cell treatments have gained negative attention for promising miraculous results. The Conner family paid nothing to participate in this study and have been promised no specific improvements.
Sitting in front of his occupational therapist last week at a Novi rehab facility, 9-year-old Kaden Strek had a choice to make: the green plastic turtle or the blue one.
"Where's the green?" asked his therapist, Sara Wasser.
After a slight pause, Kaden reached out and plucked the green turtle out of Wasser's hand. A big smile spread across his face.
"Good job!" cheered Wasser.
A year ago, Kaden, of St. Clair Shores, couldn't see most colors. Born several months premature, he suffered a severe brain bleed as an infant and was later diagnosed with spastic diplegic cerebral palsy and blindness. As a result, he could only see some shapes, colors and patterns.
Now, a year after receiving eight cord blood stem cell infusions in China, Kaden can see not only primary colors but pastels. His language has improved dramatically, and he's saying new words every day and speaking in some sentences, said his mother, Eddie (short for Elizabeth) Strek. Even his walking and balance have improved.
And his family believes stem cells have made all the difference.
"This has given him a whole new kind of independence and control over himself that he's never had," Eddie Strek said. "It's so exciting to see."
So happy with his improvement over the last year, the Streks are raising money for Kaden to go back to China for another round of stem cell therapy, hopefully next summer. They'll need about $38,000 for treatment and travel costs.
Stem cell therapy is available only for certain conditions in the United States, and cerebral palsy is not among them. The therapy has become a big business overseas, available everywhere from Mexico to Thailand.
Treatment programs are offered for a host of conditions, but they're often very expensive, and critics question their efficacy.
Beike Biotechnology, the firm that conducted Kaden's stem cell therapy, treats more than 200 international patients a month with stem cell therapy.
Researchers such as Larry Goldstein, director of the University of California San Diego's stem cell program, are very wary of overseas programs. They question where the stem cells come from and wonder about possible risks.
In a case such as Kaden's, Goldstein said it's hard to tell whether stem cells made a difference or if he improved on his own.
"That is what clinical trials are for," he said in an email last week. "Every disease fluctuates in symptoms, and kids with developmental diseases tend to continue developing albeit at different rates. How does one know whether the transplant caused improvement versus intensive physical therapy versus fluctuation versus normal developmental improvements that would have happened anyway?"
Eddie Strek disagrees. She said Kaden has received fairly extensive therapy his entire life. He now receives occupational therapy and speech therapy four days a week.
"There's just no other explanation" for his progress since the cord blood stem cell infusions, she said.
Eddie said she noticed a change in Kaden's vision within 48 hours after his first infusion in China last summer. She was talking with her husband, Tom, on Skype with Kaden next to her when Kaden wanted to get closer to the screen and was looking intently at his dad.
"He can see me!" said Tom.
Wasser, an occupational therapist with Children's Hospital of Michigan's Novi rehabilitation facility, said Kaden also is using the left side of his body now, something he didn't really do before stem cells. Kaden is the first patient Wasser has ever worked with who's had a stem cell transplant.
"I've been an OT for over 10 years, and this is the first patient I've ever had who has regained vision," Wasser said. "… For him, it's really teaching him to use something that he never had before."
That means teaching Kaden basic items such as cat, ball and bike. His mom said he knew what a cat said before, but didn't know what one looked like.
Working with Wasser during a recent therapy session, Kaden stared at an augmentative communication device the size of a laptop computer. The screen showed a grid with 15 squares. A bell popped up in one square. Kaden had to track it across the screen and tap it with a small pointer. Eventually, the grid got bigger and the bell got smaller, but he still found the bell.
Eddie Strek said it's frustrating that stem cell treatment largely isn't available in the United States, because "so many people could be helped."
"These are tangible results," Eddie Strek said. "Anyone that knew him before and sees him now, you can see the results. He's a different kid."
PS from Don Margolis: We featured Kaden last year as the family was preparing to go to China. You can find that article by putting STREK in the search box above.