Medicine University Affairs

After oesophagus, a thymus by trachea transplanters

Videregen and UCL are now making a thymus.

London’s regenerative medicine hub now brings the world yet another stem cell breakthrough: a lab-grown thymus. Successfully tested in mice, and a clinical study is already in preparation. The best of the best of British scholars and entrepreneurs stand behind it.

Announced around a year ago, this regenerative medicine achievement by stem cell researcher Paola Bonfanti was yet another one for the elite London university UCL.

A welcome respite from all that awful trachea transplant affair by UCL’s former honorary professor Paolo Macchiarini, and please don’t believe Schneider’s nasty claims that UCL professors Martin Birchall, Paolo De Coppi et al had anything to do with that. Forgotten are the horrid human experiments which in London alone killed two young women. Well, not exactly forgotten: UCL, its associated Great Ormond Street Hospital (GOSH) and their business partners Videregen are still discreetly pursuing the technology.

Birchall’s dead pigs, which kept returning to life in different papers to prove that his larynx transplants work, were officially determined to be innocent mistakes of oversight and not research misconduct. The only lesson UCL and GOSH drew from the Macchiarini affair was to deny, publicly distance, scapegoat, call Schneider a racist criminal, and hide certain PhD theses from public access for all eternity. Unlike Macchiarini’s, UCL’s own regenerative medicine is perfectly reliable, scientifically validated and saves lives, take Guardian‘s and BBC‘s word for it. Their dead trachea transplant victims are never spoken about anymore, after University of Liverpool professor Patricia Murray and myself exposed UCL’s earlier lies.

Lab-Grown Thymus

And now, a whole thymus has been grown in the lab, thanks to UCL’s stem cell researcher Bonfanti and her London colleagues. A new generation of scientific geniuses, look, no former Macchiarini collaborators contaminating the authors list:

Sara Campinoti , Asllan Gjinovci , Roberta Ragazzini , Luca Zanieri , Linda Ariza-McNaughton , Marco Catucci , Stefan Boeing , Jong-Eun Park , John C. Hutchinson , Miguel Muñoz-Ruiz , Pierluigi G. Manti , Gianluca Vozza , Carlo E. Villa , Demetra-Ellie Phylactopoulos , Constance Maurer , Giuseppe Testa , Hans J. Stauss , Sarah A. Teichmann , Neil J. Sebire , Adrian C. Hayday , Dominique Bonnet, Paola Bonfanti Reconstitution of a functional human thymus by postnatal stromal progenitor cells and natural whole-organ scaffolds Nature Communications (2020) doi: 10.1038/s41467-020-20082-7 

The Crick institute, where Bonfanti is currently on secondment, issued a press release explaining the breakthrough:

“To rebuild this organ, the researchers collected thymi from patients and in the laboratory, grew thymic epithelial cells and thymic interstitial cells from the donated tissue into many colonies of billions of cells.

The next step for the researchers was to obtain a structural scaffold of thymi, which they could repopulate with the thymic cells they had cultured. For this, researcher Asllan Gjinovci developed a new approach to remove all the cells from rat thymi, so only the structural scaffolds remained. They had to use a new microvascular surgical approach for this, as conventional methods are not effective for the thymus. 

Asllan says: “This new approach is important because it enables us to obtain scaffolds from larger organs like the human thymus, something essential to bringing this beautiful work to the clinic.”

The researchers then injected the organ scaffolds with up to six million human thymic epithelial cells as well as interstitial cells from the colonies they had grown in the lab. The cells grew onto the scaffolds and after only five days, the organs had developed to a similar stage as those seen in nine-week old foetuses. 

Finally, the team implanted these thymi into mice. They found that in over 75% of cases, the thymi were able to support the development of human lymphocytes.”

Decellurised donor organs scaffolds seeded with recipient’s own cells, where have I heard about that decell-recell approach that before….

Let me check at which GOSH department exactly Dr Bonfanti works…

UCL official profile

This charming Italian gentleman… Same paediatric thoracic surgeon Paolo De Coppi who performed trachea transplants at GOSH, once even with Macchiarini (and because that child survived, De Coppi still celebrates himself for the surgery). Do read this article on my site about De Coppi’s adventures and the organs he is growing for clinical use.

Now, you might say, this is unfair. What does Dr Bonfanti have to do with De Coppi except working in the same department? How dare I taint her research by reiterating all the misdeeds of her superior and make this strenuous connection to the Macchiarini affair? Just because Dr Bonfanti is Italian?

Let me explain myself, please.

Lab-Grown Oesophagus

In early 2017, De Coppi was poised to transplant decell-recell oesophagus into children, but that clinical trial with ten participants, announced in national media, somehow got averted in the nick of time. That was because the Macchiarini scandal just exploded beyond UCL’s and GOSH’s control, and De Coppi was asked to maybe try it with mice and pigs first. Guess who his main collaborator on these preclinical projects was.

Dr Paola Bonfanti.

In 2017, Bonfanti and De Coppi planned pig experiments with engineered oesophagus. What happened to those? Top left: GOSH press release from 2017 announcing clinical trial.

And here was the outcome, look at this joint work by De Coppi with the same Bonfanti and the same Gjinovci, celebrated 3 years ago as scientific breakthrough in all UK media. They grew an oesophagus in the lab, incidentally something which Macchiarini was last seen working on. The UCL team used decellurised rat oesophagus as a scaffold, seeded it with three types of cells and stuffed it into the abdominal fat tissue of mice.

Luca Urbani , Carlotta Camilli , Demetra-Ellie Phylactopoulos , Claire Crowley , Dipa Natarajan , Federico Scottoni , Panayiotis Maghsoudlou , Conor J. McCann , Alessandro Filippo Pellegata , Anna Urciuolo , Koichi Deguchi , Sahira Khalaf , Salvatore Ferdinando Aruta , Maria Cristina Signorelli , David Kiely , Edward Hannon , Matteo Trevisan , Rui Rachel Wong , Marc Olivier Baradez , Dale Moulding , Alex Virasami, Asllan Gjinovci, Stavros Loukogeorgakis, Sara Mantero, Nikhil Thapar, Neil Sebire, Simon Eaton, Mark Lowdell, Giulio Cossu, Paola Bonfanti, Paolo De Coppi Multi-stage bioengineering of a layered oesophagus with in vitro expanded muscle and epithelial adult progenitors Nature Communications (2018) doi: 10.1038/s41467-018-06385-w

Unlike celebrated in the media, it was not an actual oesophagus replacement transplant. That would have been too cruel, and not just because of the rat-mouse size mismatch. The mice would have died miserably as soon as they tried to eat something, which surely would have become a huge spoiler (and it possibly happened to some pigs).

But in October 2018, the world was on the verge of a revolution in transplant surgery, and De Coppi and Bonfanti were its heroes. BBC informed:

“The team hopes the research could eventually lead to clinical trials of lab-grown food pipes for children born with part of their oesophagus damaged or missing. […]

Dr Paola Bonfanti, co-author and group leader at the Francis Crick Institute and UCL Great Ormond Street Hospital Institute of Child Health (ICH), said: “We were amazed to see that our engineered tissue had both the structure and function of a healthy oesophagus, and hooked up with nearby blood vessels within a week of transplantation. […]

Prof Paolo De Coppi, co-author and consultant surgeon at Gosh, and head of stem cells and regenerative medicine at ICH, said: “This is a major step forward for regenerative medicine, bringing us ever closer to treatment that goes beyond repairing damaged tissue and offers the possibility of rejection-free organs and tissues for transplant. […]

The team at the Crick and Gosh say the [Macchiarini] scandal reinforced their determination to proceed cautiously.”

Read about De Coppi’s research here

Indeed, to create the oesophagus De Coppi and Bonfanti recruited the finest and the most qualified regenerative medicine people – some worked with Macchiarini before. Like the first author Luca Urbani, former UCL fellow, now PI at King’s College London, who also extended Birchall’s work with decell-recell muscle together with De Coppi and Gjinovci on artificial diaphragm (a project so stupid it was hopefully never tried on living things).

Another co-author of the oesophagus study was Macchiarini’s former special friend, UCL’s former star plastic trachea maker, Birchall’s PhD student and De Coppi’s former postdoc, Claire Crawley (now senior consultant at Ernst & Young).

And don’t forget a certain Mark Lowdell, the UCL professor who is growing windpipes and voiceboxes for Birchall in his special lab, so why not oesophagi also. The oesophagus paper states that Lowdell “designed the work“, which sure fills me with trust in that project. This gentleman processed trachea grafts for all transplants made at UCL and GOSH, and it seems he and Birchall haven’t given up their plans to continue, here a relevant conference abstract from 2020.

No wonder that GOSH used the occasion of that mouse study to advertise for trachea transplants in children, which apparently are still on offer:

“In the study, researchers used a rat oesophagus “scaffold” and human gut cells to grow 2cm long engineered tubes of oesophagus. These tubes were implanted into mice and within a week the engineered tissue developed its own blood supply, which is important for a healthy gut that can squeeze down food.

GOSH has already started using similar tissue products in children. GOSH has already done three successful stem-cell trachea transplants. GOSH was the first children’s hospital in the world to do so and remains the only children’s hospital to do this work”

That linked claim is a lie. At least one of these 3 patients, the 15 year old Shawna, died right away, and she only got operated because GOSH surgeons lied to her mother. The medical history and the fates of the two others are closely guarded secrets. The lone survivor Ciaran is still being paraded as a success story to recruit funders and clients. Just in 2019, De Coppi was praising his trachea and oesophagus transplant technology for the Emirates franchise of GOSH :

a trachea or oesophagus that is made from stem cells and grows with the child is a much better and kinder option for the child.

(see page 37-38 here)

Another co-author of the oesophagus paper, who also “designed the work“: Giulio Cossu, former UCL professor, who was whitewashed of research misconduct by his London employer in 2013. Cossu currently sports 17 papers on PubPeer, some with rather serious falsifications, which once served to earn him a reputation of science genius who can cure for muscular dystrophy (in dogs). In 2017, this regenerative medicine researcher signed a white paper in The Lancet, insisting, together with the Birchall and De Coppi that Macchiarini’s technology works while calling for more human experimenting.

Strangely, Birchall wasn’t involved in the oesophagus project, despite a long past collaboration with De Coppi on this very topic. Maybe Birchall became a toxic liability, blame me if you like. But in 2012, on the peak of Macchiarini’s plastic trachea fame, the two UCL surgeons announced (in a predatory journal) “A new approach for esophageal replacement“:

“Decellularized matrices have been recently suggested as the optimal choice for scaffolds, but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution.”

With such a crack team of trustworthy experts, De Coppi’s and Bonfanti’s oesophagus project was bound to revolutionise transplant surgery and succeed where that fraudulent Macchiarini failed. I mean, the results were so convincing, De Coppi even all but advertised them to paying patients in the Emirates.

Change of Plans

And yet, UCL’s mouse experiments with the lab-grown oesophagus must have been so convincing, successful, and groundbreaking that nobody is talking about oesophagus clinical trials anymore. Even the pig experiments (“Oesophagus tissue engineering in large animals as preclinical model for the treatment of
oesophageal atresia
“), scheduled already in 2017, were either cancelled for being too cruel and pointless, or produced “unpublishable” results, that is why you never heard of them. Actually yes, why aren’t Drs Bonfanti and de Coppi telling us what happened to those pigs? Are they afraid we won’t be able to stomach it? Surely GOSH’s patients in London and Emirates would like to know before agreeing to become compassionately used.

The clinical trial, announced 4 years ago as about to start right away, hasn’t even been preregistered so far, meaning it is not planned, not in the foreseeable future, quite possibly for very good reasons. The London scholars are now focussing on other organs. I suspect that Bonfanti will soon turn her attention to decell-recell pancreas to cure mice of diabetes for her next Nature Communications paper.

De Coppi is presently doing in vitro research with “mini-stomachs”, clumps of gastric cells, and he just announced to deploy his scientific genius to fight COVID-19 and its impact on the digestive system. The GOSH surgeon was quoted in that recent interview from January 2022 with even grander plans:

“The second direction is within regenerative and tissue engineering in which we are trying to create a more complex mini stomach that could be used to replace missing stomachs in both adults and children.”

Huh? No more decell-recell technology, what happened, Dr De Coppi? Instead a giant human stomach growing in a petri dish? I think this is Aperol talking.

These lab-grown stomachs must be the logical extension from the facts that De Coppi’s trachea transplants failed disastrously and his oesophagus transplants were cancelled before children could get hurt. He needs a new organ to bullshit about, so why not stomach. And as for thymus… Like all the other former Macchiarini associates, De Coppi is not even part of that recent thymus paper by his subordinate Bonfanti. Maybe De Coppi became toxic, just like Birchall before him. Feel free to blame me again.

Paolo De Coppi receives in the operating room the trachea graft which then killed the 15 year old Shawna. Still from the BBC documentary “Great Ormond Street Series 2, ‘Experimental Surgery”

Industry Partner from Hell

But let me tell you who did not become toxic, no matter what. The recent press release by The Crick continues:

Paola Bonfanti, senior author and group leader at the Crick and professor in the Division of Infection and Immunity at UCL says: “As well as providing a new source of transplants for people without a working thymus, our work has other potential future applications.

“For example, as the thymus helps the immune system to recognise self from non-self, it poses a problem for organ transplants as it can cause the immune system to attack the transplant. 

“It is possible that we could overcome this by also transplanting a thymus regrown from cells taken from the thymus of the organ donor.”

The potential clinical applications are not that far away! Nature Communications paper mentions that “P.B. and A.G. are named inventors of patent application no. PCT/GB2019/051310“, the patent is for the method of tissue decellurisation. It is already being developed for clinical use. But if you thought that with the thymus project Dr Bonfanti ceased her collaboration with those horrid trachea transplanters: wrong.

Observe, a newly funded research project for “clinical translation of bioengineered thymus for complete DiGeorge syndrome” (a genetic defect which can cause a total absence of a thymus). The 2 year funding period (almost £400k) began in November 2021:

Clinical translation of bioengineered thymus for complete DiGeorge syndrome

This project will focus on the translation of world-leading UK research into robust manufacturing processes ready for a future clinical trial to treat a life-threatening disease in infants. Babies born without a thymus gland (called complete DiGeorge Syndrome) have a fatally deficient immune system, and without treatment will die within 2-3 years.

The project uses ground-breaking technology to create a new thymus using biological tissue scaffolds and thymus cells. Laboratory research has shown that this bioengineered thymus can provide the immune system functions that are lacking in infants born without a functioning thymus. During the project research work will generate data to support the manufacture, quality, safety and efficacy of a bioengineered thymus…”

Guess which company is tasked by UCL with bringing this technology to the market. Videregen.

The same Liverpool startup by Steve Bloor which licenced UCL’s trachea transplant technology for clinical application and sponsored trials (with UK and EU tax money), and which previously set lawyers upon Patricia Murray, trying to get the University of Liverpool to sack or at least to silence her, fortunately unsuccessfully.

Murray is still trying to prevent Videregen’s clinical trial in London with decell-recell airway patches for bronchopleural fistula patients (she got Videregen’s trachea transplant clinical trials cancelled or suspended), but the Royal Papworth hospital and the national authority MHRA seem inclined to proceed. The clinical trial NCT04435249 is however still “not yet recruiting“.

Videregen should have gone bankrupt years ago, when Murray and yours truly succeeded in derailing their three EU and UK-funded airway transplant clinical trials with around 60 patients in total before anyone got hurt. In 2016, Videregen received an orphan designation from EMA to market their decell-recell trachers for clinical use in the European Union. The EU permission was never revoked, but for lack of clinical partners Videregen gave up, last year they closed their EU franchise. Their business is now focussed on free Brexited Britain.

A company like Videregen shouldn’t be touched with a barge pole, scientists seen collaborating with this business are tainted by association. Videregen only survived because it keeps receiving UK governmental grants for clinical studies and because UCL supports them. Like for the new clinical projects for bronchopleural fistula, and for the bioengineered thymus.

Bonfanti and Gjinovci never replied to my email, apparently they have no qualms outsourcing their patented technology to Videregen.

To be fair, the thymus method might indeed work, to a degree. But not thanks to the decell-recell scaffolds, those always proved a total failure in real life (as opposed to peer-reviewed literature). In October 2021, FDA approved a cell therapy for congenital athymia (Rethymic), where thymus cells from a human donor are implanted, allegedly it “takes six months or longer to reconstitute the immune function in treated patients“. If that works, there is a theoretical potential for Bonfanti’s method to work, but there is no need or use for a decellularised scaffold. But UCL and their trusty ally Videregen always placed money over patients’ need and safety.

These clinical trials by Videregen will be difficult to stop. UK Government just announced to use Brexit freedom to “liberalise” clinical trial regulations, i.e., to sell Britain’s populace for medical experiments. As I predicted already in 2016, in the context of Videregen’s trachea transplant trials.


One-Time
Monthly

I thank all my donors for supporting my journalism. You can be one of them!
Make a one-time donation:

I thank all my donors for supporting my journalism. You can be one of them!
Make a monthly donation:

Choose an amount

€5.00
€10.00
€20.00
€5.00
€10.00
€20.00

Or enter a custom amount


Your contribution is appreciated.

Your contribution is appreciated.

DonateDonate monthly

14 comments on “After oesophagus, a thymus by trachea transplanters

  1. “Another co-author of the oesophagus paper, who also “designed the work“: Giulio Cossu, former UCL professor, who was whitewashed of research misconduct by his London employer in 2013. Cossu currently sports 17 papers on PubPeer, some with rather serious falsifications, which once served to earn him a reputation of science genius who can cure for muscular dystrophy (in dogs).”

    https://www.research.manchester.ac.uk/portal/en/researchers/giulio-cossu(b542484b-79c3-48ce-bab9-ed95675a1db9).html

    https://pubpeer.com/search?q=giulio+cossu

    https://www.research.manchester.ac.uk/portal/en/researchers/silvia-bulfonepaus(a3522301-fb82-4a4b-92c7-c2e44c64ccdb).html

    13 retractions

    https://www.statnews.com/2016/06/24/science-fraud-second-chance/

    https://pubpeer.com/search?q=bulfone-paus

    http://retractiondatabase.org/RetractionSearch.aspx#?auth%3dBulfone-Paus%252c%2bSilvia

    https://www.research.manchester.ac.uk/portal/en/researchers/paul-townsend(38f8617a-b808-4372-bd02-b3fa9477fafa).html

    “I am a fully tenured Principal Investigator, Associate Dean of Business Engagement, co-Director of Manchester Centre for Cellular Metabolism, I am Professor of Molecular Cell Biology, Division of Cancer Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester. I act as one of the key university conduits for the CRUK Manchester Institute, Medicines Discovery Catapult and I am the Industry Lead for the Manchester BRC and Manchester academic lead for Singapore. I am also a PI in the Manchester Cancer Research Centre and hold adjunct professorships in Athens and Singapore.”

    4 retractions

    https://pubpeer.com/search?q=townsend+latchman

    http://retractiondatabase.org/RetractionSearch.aspx#?auth%3dTownsend%252c%2bPaul%2bA

    Like

    • “Another co-author of the oesophagus paper, who also “designed the work“: Giulio Cossu, former UCL professor, who was whitewashed of research misconduct by his London employer in 2013. Cossu currently sports 17 papers on PubPeer, some with rather serious falsifications, which once served to earn him a reputation of science genius who can cure for muscular dystrophy (in dogs).”

      Offshoot at University of Leuven, Belgium.

      https://generateyourmuscle.com/team/university-of-leuven/

      “Maurilio Sampaolesi, full professor in Stem Cell and Developmental Biology, was among the first to recognize, demonstrate and improve the therapeutic potential of mesoangioblasts in the treatment of genetic muscular dystrophies.”

      Take a look:

      https://pubpeer.com/search?q=Sampaolesi

      Like

  2. From Covid-19 to esophagus and thymus this is the current state of science

    Like

  3. I thought this sounded familiar. Rethymic is the commercial (read “cleaned up”) version of what Duke has been doing for nearly 30 years: https://www.statnews.com/2019/12/06/families-reeling-after-fda-rejects-therapy-for-kids-without-thymus/

    It’s hard to see what decell-recell would add.

    Like

  4. A new thymus… neat and this time even without shooting lasers through your chest wall.
    (‘It is possible to directly irradiate the thymus with a focused laser spot through the chest wall’ citation 106)
    https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC5995606/

    And now… something completely different:
    Academic Journal Claims it Fingerprints PDFs for ‘Ransomware,’ Not Surveillance
    https://www.vice.com/en/article/4aw48g/academic-journal-claims-it-fingerprints-pdfs-for-ransomware-not-surveillance

    Like

  5. Lee Rudolph

    Why don’t the Lab-Grown Meat Boys get together with the Thymus Gland Gang? Every gourmet loves a good Ris de Veau à la Financière!

    Like

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: