Tag Archives: Andemariam Teklesenbet Beyene

Trachea transplants: an update

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I got curious the other day about trachea transplants, a topic I first wrote about one an Aug. 22, 2011 posting featuring Andemariam Teklesenbet Beyene and wondered how things had worked out for him. For anyone who doesn’t know the story, ,

In early July 2011, there were reports of a new kind of transplant involving a body part made of a biocomposite. Andemariam Teklesenbet Beyene underwent a trachea transplant that required an artificial windpipe crafted by UK experts then flown to Sweden where Beyene’s stem cells were used to coat the windpipe before being transplanted into his body.

It is an extraordinary story not least because Beyene, a patient in a Swedish hospital planning to return to Eritrea after his PhD studies in Iceland, illustrates the international cooperation that made the transplant possible.

The scaffolding material for the artificial windpipe was developed by Professor Alex Seifalian at the University College London in a landmark piece of nanotechnology-enabled tissue engineering. Tim Harper in his July 25, 2011 posting provides more details about the scaffolding,

A team led by Professor Alexander Seifalian (UCL Division of Surgery & Interventional Science; professor of nanotechnology and regenerative medicine at University College London, UK), whose laboratories are headquartered at the Royal Free Hospital, created a glass mold of the patient’s trachea from X-ray computed tomography (CT) scans of the patient. In CT, digital geometry processing is employed to generate a 3D image of the inside of an object from a large series of 2D X-ray images taken around one single axis of rotation.

Then, they manufactured a full size y-shaped trachea scaffold at Professor Seifalian’s laboratories. The scaffold of the trachea was built using a novel nanocomposite polymer developed and patented by Professor Seifalian. Professor Seifalian worked together with Professor Paolo Macchiarini at Karolinska Institutet, Stockholm, Sweden (who also holds an Honorary appointment at UCL).

…

What I didn’t realize in 2011 was there had been some earlier transplants as Gretchen Vogel writes in her April 19, 2013  article (Trachea Transplants Test the Limits) which summarizes and critiques the work* on synthesized tracheas to date for Science magazine (the article is behind a a paywall),

More than a dozen ill people have received a bioengineered trachea seeded with stem cells during the past 5 years, but outcomes are mixed, and critics say the treatment may not do what its developers claim.

…

Although at first glance the trachea might seem like a simple tube, its thin but cartilage-reinforced walls must stand up to near-constant use as a person breathes, clears his throat, or coughs. Any transplant, therefore, has to be strong enough to withstand such pressures without collapsing. But a rigid prosthesis can rub against and damage the adjacent major blood vessels in the upper part of the chest, leaving a patient at risk for a fatal hemorrhage. At the same time, the natural blood supply for the trachea’s tissues is intricate, with vessels too small for surgeons to easily reconnect during a transplant operation. And because it is exposed to inhaled air, the wound between the implant and the remaining airway is especially vulnerable to infection.

Surgeons have tried for years to find ways around these challenges, without much success. When Castillo (Claudia Castillo,  first patient to receive a trachea transplant using her own stem cells) was hospitalized in Barcelona in March 2008, Macchiarini [Paolo Macchiarini], who was then at the University of Barcelona’s Hospital Clínic, and Birchall [Martin Birchall], then at the University of Bristol in the United Kingdom, had experimented with bioengineered transplants in pigs. They would take a trachea from a pig and remove its living cells to create a so-called decellularized scaffold. They seeded this with cells from the recipient pig: bone marrow cells on the outer layer, thought to help form new cartilage, and epithelial cells on the inside, which they hoped would regrow the trachea’s lining. They allowed the cells to grow on the scaffold for several days in a bioreactor designed to provide different conditions for the two types of cells. They hoped that the decellularized scaffold would not require immunosuppressive drugs to prevent its rejection and that the seeded cells would take over the removed cells’ roles, ultimately forming a living organ.

The main difference between the 2008 Castillo operation and the 2011 Teklesenbet Beyene,operation is the scaffolding. For Castillo, they used a cadaverous** trachea where living cells were removed to create a ‘decellularized’ scaffold. For Teklesenbet Beyene, they used a nanocomposite** polymer. According to Vogel, 14 people have had the operation using either the decellularized or the nanocomposite composite polymer as the base for a new trachea. There have been some problems and deaths although Castillo who is still alive did not respond to any of Vogel’s requests for a comment . As for Teklesenbet Beyene (from the article),

His current doctor, Tomas Gudbjartsson of Landspitali University Hospital in Reykjavik, tells Science that Beyene has had several stents, but is healthy enough that he was able to complete his studies last year [2012]. The researchers have mentioned other patients in passing in several papers, but no formal reports have been published about their health, and Science has not been able to independently verify the current status of all the patients.

Both Birchall and Macchiarini have received grants for clinical trials,

In March [2013?[, Birchall received a £2.8 million ($4.3 million) grant from the United Kingdom’s Medical Research Council to conduct a trial of decellularized and stem cell–seeded upper trachea and larynx, with roughly 10 patients. Macchiarini has already completed two transplants in Russia as part of a clinical trial—funded with a $6 million grant from the Russian government—that he says should eventually enroll 20 or 25 patients. “We were allowed to do this type of transplantation only in extreme cases,” he says. “The clinical study for the first time gives us a chance to include patients who are not in such critical shape.”

Macchiarini is also the lead investigator on a 5-year, €4 million ($5.2 million) grant from the European Union to begin a clinical trial using decellularized tracheas and further develop the polymer scaffolds in large animal models. That project may need to be reorganized, however, following a legal dispute last year in Italy, where the transplants were supposed to take place—Macchiarini had a part-time position at Careggi Hospital in Florence. In September, however, Italy’s financial police accused him of attempted extortion, and briefly placed him under house arrest, for allegedly telling a patient that he could receive treatment in Germany for €150,000. Macchiarini and his lawyer say that he was simply informing the patient of possible options, not demanding payment. The main charges were soon dropped, but Macchiarini says that the charges stemmed from academic politics in Tuscany and he has severed ties with the hospital and university there. “There is no way to go back there.”

That last bit (in the excerpt) about academic politics in Tuscany seems downright Machiavellian (Wikipedia essay on Machiavelli here).

Getting back to the trachea transplants, there seems to be a major difference of opinion. While the researchers Macchiarini and Birchall have opted for human clinical trials other experts are suggesting that animal trials should be the next step for this research. I recommend reading Vogel’s article so you can fully appreciate the debate.

*’which a summary and critique of the work’ changed to ‘which summarizes and critiques the work’ for grammatical correctness on April 8, 2016.

**’pig trachea’ changed to ‘cadaverous trachea’ and ‘nanocompostie’ changed to ‘nanocomposite’ on April 19, 2016.

New type of scaffolding for tissue engineering

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Since the international July 2011 coverage of Andemariam Teklesenbet Beyene’s synthetic trachea transplant (mentioned in my Aug. 2, 2011 posting), I’ve been quite interested in tissue engineering. Scientists at Northwestern University (US) have developed a new type of scaffolding for tissue engineering.

There’s a description in the Feb. 12, 2012 news release on EurekAlert of  tissue engineering and scaffolding and some of the disadvantages with the current technology,

Through tissue engineering, researchers seek to regenerate human tissue, such as bone and cartilage, that has been damaged by injury or disease. Scaffolds — artificial, lattice-like structures capable of supporting tissue formation — are necessary in this process to provide a template to support the growing cells. Over time, the scaffold resorbs into the body, leaving behind the natural tissue.

Scaffolds are typically engineered with pores that allow the cells to migrate throughout the material. The pores are often created with the use of salt, sugar, or carbon dioxide gas, but these additives have various drawbacks; They create an imperfect pore structures and, in the case of salt, require a lengthy process to remove the salt after the pores are created, said Guillermo Ameer, professor of biomedical engineering at the McCormick School of Engineering and professor of surgery at the Feinberg School of Medicine.

The new scaffolds are more flexible and can be tailored to ‘resorb’ at different times,

The new scaffolds, created from a combination of ceramic nanoparticles and elastic polymers, were formed in a vacuum through a process termed “low-pressure foaming” that requires high heat, Ameer said. The result was a series of pores that were highly interconnected and not dependent on the use of salt.

The new process creates scaffolds that are highly flexible and can be tailored to degrade at varying speeds depending on the recovery time expected for the patient. The scaffolds can also incorporate nano-sized fibers, providing a new range of mechanical and biological properties, Ameer said. [emphasis mine]

I wonder what “new range of mechanical and biological properties” will be enabled; I was not able to find any speculation.

In the meantime, here’s an image of the scaffolding from the McCormick School (at Northwestern University) http://www.mccormick.northwestern.edu/news/articles/article_1043.html,

For anyone who’s interested in an update on Andemariam Teklesenbet Beyene, according to this Dec. 9, 2011 posting on StemSave, he’s doing well.

ETA Feb. 14, 2012: Michael Berger at Nanowerk has written an article titled, Tissue engineering of 3D tubular structures, which provides some insight into another aspect of creating scaffolding, the tubular nature of many of our organs.

Body parts nano style

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In early July 2011, there were reports of a new kind of transplant involving a body part made of a biocomposite. Andemariam Teklesenbet Beyene underwent a trachea transplant that required an artificial windpipe crafted by UK experts then flown to Sweden where Beyene’s stem cells were used to coat the windpipe before being transplanted into his body.

It is an extraordinary story not least because Beyene, a patient in a Swedish hospital planning to return to Eritrea after his PhD studies in Iceland, illustrates the international cooperation that made the transplant possible.

The scaffolding material for the artificial windpipe was developed by Professor Alex Seifalian at the University College London in a landmark piece of nanotechnology-enabled tissue engineering. Tim Harper in his July 25, 2011 posting provides more details about the scaffolding,

A team led by Professor Alexander Seifalian (UCL Division of Surgery & Interventional Science; professor of nanotechnology and regenerative medicine at University College London, UK), whose laboratories are headquartered at the Royal Free Hospital, created a glass mold of the patient’s trachea from X-ray computed tomography (CT) scans of the patient. In CT, digital geometry processing is employed to generate a 3D image of the inside of an object from a large series of 2D X-ray images taken around one single axis of rotation.

Then, they manufactured a full size y-shaped trachea scaffold at Professor Seifalian’s laboratories. The scaffold of the trachea was built using a novel nanocomposite polymer developed and patented by Professor Seifalian. Professor Seifalian worked together with Professor Paolo Macchiarini at Karolinska Institutet, Stockholm, Sweden (who also holds an Honorary appointment at UCL).

Professor Seifalian and his team used a porous novel nanocomposite polymer to build the y-shaped trachea scaffold. The pores were millions of little holes, providing this way a place for the patient’s stem cells to grow roots. The team cut strips of the novel nanocomposite polymer and wrapped them around the glass mold creating this way the cartilage rings that conferred structural strength to the trachea.

After the scaffold construct was finished, it was taken to Karolinska Institutet where the patient’s stem cells were seeded by Professor Macchiarini’s team.

Harper goes on to provide more details and insight into what makes this event such an important one.

Meanwhile, Dexter Johnson’s (Nanoclast blog in the IEEE website) July 21, 2011 posting poses a question,

While the nanocomposite scaffold is a critical element to the artificial organ, perhaps no less important was the bioreactor used to grow the stem cells onto it, which was developed at Harvard Bioscience.

If you needed any evidence of how nanotechnology is not only interdisciplinary, but also international, you could just cite this case: UK-developed nanocomposite for the scaffolding material, US-based bioreactor in which the stem cells were grown onto the scaffolding and a Swedish-based medical institute to perform the transplant.

So I ask, which country or region is going to get rich from the breakthrough?

It’s an interesting question and I don’t think I would have framed it in quite that fashion largely because I don’t tend to think of countries or regions getting wealthy from biomedical products since pharmaceutical companies tend to be internationally based. Is Switzerland richer for Novartis?

I suppose I’m a product of the Canadian landscape from which I spring so I think of trees and mines as making a country or region richer as they are inextricably linked to their environment but pharmaceuticals or biomedical appliances can be manufactured anywhere. Consequently, a synthetic organ could be manufactured anywhere once the technology becomes easily available. Who gets rich from this development? I suspect that will be a person or persons if anyone but, not a region or a country.

Getting back to Beyene, here are more details from the July 7, 2011 BBC News article by Michelle Roberts,

Dr Alex Seifalian and his team used this fragile structure [the scaffold] to create a replacement for the patient, whose own windpipe was ravaged by an inoperable tumour.

Despite aggressive chemotherapy and radiotherapy, the cancer had grown to the size of a golf ball and was blocking his breathing. Without a transplant he would have died.

During a 12-hour operation Professor Macchiarini removed all of the tumour and the diseased windpipe and replaced it with the tailor-made replica [now covered with tissue grown from the patient’s bone marrow tricked into growing like cells found in a trachea].

…

And, importantly, Mr Beyene’s body will accept it as its own, meaning he will not need to take the strong anti-rejection drugs that other transplant patients have to.

Professor Macchiarini said this was the real breakthrough.

“Thanks to nanotechnology, this new branch of regenerative medicine, we are now able to produce a custom-made windpipe within two days or one week.

“This is a synthetic windpipe. The beauty of this is you can have it immediately. There is no delay. This technique does not rely on a human donation.”

He said many other organs could be repaired or replaced in the same way.

A month on from his operation, Mr Beyene is still looking weak, but well.

Sitting up in his hospital bed, he said: “I was very scared, very scared about the operation. But it was live or die.”

My best wishes to Beyene and his family who are also pioneers.