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.”
The Baldwin County doctor that treated former Alabama football players with adult stem cells also has treated at least two people diagnosed with amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease.
One of the ALS patients, former NFL football player and college coach Frank Orgel, recently underwent a new stem cell reprogramming technique performed by Dr. Jason R. Williams at Precision StemCell in Gulf Shores.
Former NFL football player and college coach Frank Orgel has been struggling with ALS for about eight years. (photo courtesy Precision StemCell)
Before the injections, Orgel’s health had declined. He could not move his left arm or leg. He couldn’t walk or stand on his own, he said.
Within a few days of having the stem cell treatment, Orgel’s constant muscle twitching diminished, said Bob Hubbard, director of stem cell therapy at the practice. Within weeks, he was able to walk in a pool of water and stand unassisted.
“I think it’s helped me,” said Orgel, who was a defensive coordinator at Auburn under former head coach Pat Dye. “I’m walking in the pool and I used to drag my feet. Now my left leg is picking up.”
ALS is a progressive neuro-degenerative disease that affects nerve cells in the brain and the spinal cord. The progressive degeneration of the motor neurons in ALS eventually leads to death, according to the ALS Association.
Stem cells, sometimes called the body’s master cells, are precursor cells that develop into blood, bones and organs, according to the U.S. Food and Drug Administration, which regulates their use. Their promise in medicine, according to many scientists and doctors, is that the cells have the potential to help and regenerate other cells.
While Williams’ treatments are considered investigational, he has said, they meet FDA guidelines because the stem cells are collected from a patient’s fat tissue and administered back to that patient during the same procedure.
Orgel, 74, said Williams told him it would take between eight months to a year for his nerves to regrow. He is traveling to Gulf Shores from his home in Albany, Ga., this weekend for another stem cell treatment, Orgel said: “I need to get to where I can walk.”
In recent years, Orgel has gone to Mexico at least three times for different types of treatments, not sanctioned in the U.S. At least once, he said, he had placenta cells injected into his body. “That didn’t work,” Orgel said. “I didn’t feel any better.”
These days, he’s lifting weights and swimming twice a week as part of a physical therapy regimen.
Stem cell therapies
The technique performed on Orgel is called InVivo reprogramming, Hubbard said, which is described as reprograms adult stem cells into neural stem cells.
The procedure involves harvesting adult stem cells from the patient’s own fat, which Williams obtains through liposuction. Then, he uses image-guided therapy to insert the stem cells into the patient’s spine.
The patient is prescribed an oral medication that, as laboratory research has shown, causes stem cells to reprogram, converting them into neural stem cells, according to a written statement from the Gulf Shores medical practice.
Because of their experimental nature, stem cell injections to remedy conditions such as damaged knee joints or injured muscles are not covered by insurance. A typical stem cell therapy with Williams costs about $15,000. The collection of the cells through liposuction, he has said, makes up about half of the overall price.
Williams, a board-certified radiologist, said in a previous Press-Register interview that he spent about four years researching various stem cell therapies, including those collected from bone marrow. He said that the adult stem cells derived from fat tissue seemed to bring fewer chances for complications.
Harvesting stem cells from a patient’s own fat removes the need to culture cells, Williams said earlier this year, explaining that culturing stem cells can be a weeks-long process that may expose patients to risks such as infection.
In recent years, professional athletes such as Denver Broncos quarterback Peyton Manning and New York Yankees pitcher Bartolo Colon, among dozens of others, have acknowledged seeking stem cell injections outside the U.S. to try to help heal injuries.
FDA urges caution
Earlier this year, the FDA issued a consumer warning about claims regarding stem cells. In it, Stephanie Simek, deputy director of the FDA’s Office of Cellular, Tissue and Gene Therapies, said that stem cells from bone marrow or blood are routinely used in transplant procedures to treat cancer and disorders of the blood and immune system.
The document cautioned consumers, however, to make sure that stem cell therapy treatments have been approved by the FDA or are being studied under a clinical investigation allowed to proceed by the agency. “There is a potential safety risk when you put cells in an area where they are not performing the same biological function as they were when in their original location in the body,” Simek said.
Cells in a different environment may multiply, form tumors, or may migrate elsewhere in the body from the spot where they were placed, according to the FDA warning.
While several dozen clinical trials involving various forms of stem cell therapies are under way or have been announced around the world, few have included adult stem cells found in fat tissue.
Williams has said that universities and research groups have been slow to move forward because research funding tends to steer toward new drug therapies. He said that he is up front with his patients, telling them that results cannot be predicted.
“This new technique of InVivo reprogramming shows great promise for possibly repairing or regenerating nerve cells,“ Williams said in a written statement. “That means it may open up opportunities for treating several neural conditions such as spinal cord injury, stroke, Parkinson’s and Alzheimer’s disease.”
Williams said the new technique has been shown to help increase the number of neural stem cells that are transferred back into a patient.
“We are hopeful this will indeed help us heal or regrow nerve cells,” Williams said. “However, it is still too soon to really know.”
BODY DIES, STEM CELLS GO DORMANT AND SURVIVE FOR 2+ WEEKS
"Scientists around the world are shocked, but they shouldn't be," says Don Margolis
Under the direction of Fabrice Chrétien, in collaboration with Shahragim Tajbakhsh, researchers from the Institut Pasteur, the Université de Versailles Saint-Quentin-en-Yvelines, the Paris Public Hospital Network (AP-HP), and the CNRS have shown for the first time in humans and mice, the capacity of stem cells to adopt a dormant state when their environment becomes hostile, including several days after death. This ability to significantly reduce metabolic activity enables them to preserve their potential for cellular division, even after extended periods post mortem. After isolation, they can then be used to repair damaged organs or tissues. This discovery could lead to new therapeutic avenues for treating numerous diseases. The study is being published in the journal Nature communications.
Remarkably, skeletal muscle stem cells can survive for seventeen days in humans and sixteen days in mice, post mortem well beyond the 1-2 days currently thought. This discovery was made by researchers from the Institut Pasteur, the Université de Versailles Saint-Quentin-en-Yvelines, the Paris Public Hospital Network (AP-HP), and the CNRS under the direction of Professor Fabrice Chrétien*, in collaboration with a team led by Professor Shahragim Tajbakhsh**. The scientists were also able to show that these stem cells, once back in culture, retained their capacity to differentiate into perfectly functioning muscle cells.
In light of this astonishing result, scientists then sought to characterize these cells to understand how they survive in such adverse conditions. They observed that these cells enter a deeper state of quiescence, drastically lowering their metabolism. This so-called "dormant" state is a result of cellular organization that is stripped to the bare minimum: fewer mitochondria (cellular power plants using oxygen to produce energy in cells) and diminished stores of energy.
“We can compare this to pathological conditions where cells are severely deficient in resources, before regaining a normal cell cycle for regenerating damaged tissues and organs, explains Fabrice Chrétien. When muscle is in the acute phase of a lesion, the distribution of oxygen is highly disrupted. We have even observed that muscle stem cells in anoxia (totally deprived of oxygen) at 4°C have a better survival rate than those regularly exposed to ambient levels of oxygen.”
The team of Fabrice Chrétien then wondered if these results were consistent with other cell types. Tests were then done on stem cells taken from bone marrow where blood cells are produced. These cells remained viable for four days in post mortem mice models, and more importantly, they retained their capacity to reconstitute tissue after a bone marrow transplant.
This discovery could form the basis of a new source, and more importantly new methods of conservation, for stem cells used to treat a number of pathologies. This is the case for leukemia, for example, which requires a bone marrow transplant to restore a patient's blood and immune cells destroyed by chemotherapy and radiation. By harvesting stem cells from the bone marrow of consenting donors post mortem, doctors could address to a certain extent the shortage of tissues and cells. Although highly promising, this approach in the realm of cellular therapy still requires more testing and validation before it can be used in clinical applications. Nevertheless, it paves the way to investigate the viability of stem cells from all tissues and organs post mortem.
From Don: "Scientists around the world are shocked, but they shouldn't be, because Repair Stem Cells are created to divide, grow and cure, no matter what the obstacles. There are many many obstacles which can slow or stop that repair, but we are constantly finding ways around them. Now we know it will be possible in the future to collect stem cells (which are smart enough to go dormant) from a recently deceased body, test them, and use them to help another patient."
Prof Colin McGuckin, director of the newly launched Adult Stem-cell Foundation of Ireland, said debate was needed on the controversial issue for the health of Irish citizens
A world expert on adult stem cell research has warned Ireland must look to the future to protect the population.
Prof Colin McGuckin, director of the newly launched Adult Stem-cell Foundation of Ireland, said debate was needed on the controversial issue for the health of Irish citizens. Prof. Mc Guckin was the ONLY stem cell doctor in the United Kingdom to tell the truth about the embryonic hoax back in 2009 and was forced out of Newcastle U. for his honesty. He has been constantly praised by the Repair Stem Cell Institute. We are thrilled to see this great research scientist take on those who would keep real stem cells away from those who need them.
The Vatican’s adviser on stem cell issues said like all countries in Europe, Ireland must be ready for new treatments. Ireland has, up to now, suffered with nothing but false stem cell information available in its media, promoted by those who do not want adult stem cells to interfere with their huge profits on pills and expensive, usually dangerous treatments.
“We cannot simply look back and say, ‘I wish we had prepared for that’,” said Prof McGuckin. “In my career, I worked with children who would be alive today if more stem cell banks had been available.”
The foundation is dedicated to providing awareness and information about adult stem cells, research, development and therapies, as well as supporting people in need of or undergoing stem cell therapy.
It will also back the development of an all-Ireland stem cell bank and to support adult stem cell research and development.
Prof McGuckin believes Ireland must fund adult stem cell research and be ready to understand the socio-economic issues surrounding cellular therapy, stem cell banking, facilities provision, law and the relevant medical technology.
Adult stem cells are found in bone marrow, peripheral blood, umbilical cord blood, skeletal muscle, skin and teeth. They have been used to successfully treat leukaemia and related blood cancers for years.
Umbilical cord blood and bone marrow treatments have seen the highest success rate to date and can treat leukaemia, lymphoma, sickle cell disease, thalassaemia and immune deficiencies.
More than 70 diseases are treatable with cord blood and over 15 clinical trials are under way for new conditions.
Prof McGuckin said umbilical cord blood, with 130 million births per year, remains the most available stem cell source.
“The health of Irish citizens demands that we debate now what we can do and umbilical cord blood and adult stem cells must be part of that debate,” added the director of the Cell Therapy Research Institute in Lyon, France.
Prof McGuckin’s research group was the first to identify a rare group of cells with similar characteristics to embryonic stem cells and to develop them into non-blood tissues such as liver, brain and pancreas.
His latest clinical trial includes the use of a child’s own cord blood for the treatment of severe neonatal hypoxia, which may lead to cerebral palsy.
He is also developing a treatment for children with congenital bone malformations such as cleft palate, using the child’s own mesenchymal stem cells to make bone implants.