Bioengineered tissue transplant saves a life

There is a story on the wires today about an upcoming Lancet article describing the case of a young Columbian woman whose failing airway was replaced by a bioengineered airway whose cells were cultured from adult stem cells obtained from the patient's bone marrow. Since there is as yet no scientific paper, I got these details from a press release from the University of Bristol, one of four participating European universities in this unique case (the others were in Barcelona, Padua and Milan).

The 30 year old patient's main airway (the lower trachea) and left main stem bronchus (one of the two branches, to the right and left lungs) had been destroyed by TB and she was so short of breath she could no longer care for her children or perform normal activities of daily life. The technique was to use a cell free skeleton of the tracheal and bronchial segments (obtained from a Spanish donor who died of a stroke) and repopulate it with pluripotent stem cells obtained from the patient's bone marrow. The stem cells were then grown in the laboratory of Professor Martin Birchallat the University of Bristol and then matured into chondrocytes. This was a technique used to treat osteoarthritis in another laboratory. In osteoarthritis the cartilage of the joint surfaces is worn off and this was seen as a way to replace them. Use to grow an airway was a new application and in this case saved this young mother's life.

The donor trachea was first denuded of its cells so that there would be no foreign antigens to provoke a graft rejection. That took about 6 weeks. It was then seeded on the outside of the cartilage skeleton with the patient's newly grown chondrocytes, using a bioreactor developed at the Politecnico di Milano, Italy. The chondrocytes migrated into the interior of the cartilage skeleton which was seeded with epithelial cells under defined conditions to allow the development of each individual cell type. The result was a bioengineered traceal-bronchial graft containing the patient's cells. It was transplanted into the patient in June of this year.

It not only saved her life, it seems to have given her a normal life back again:

Professor Macchiarini, lead author on the paper, said: "We are terribly excited by these results. Just four days after transplantation the graft was almost indistinguishable from adjacent normal bronchi. After one month, a biopsy elicited local bleeding, indicating that the blood vessels had already grown back successfully".


The patient, Claudia Castillo, a young woman from Colombia but now living in Spain, had no complications from the operation and was discharged from hospital on the tenth post-operative day. She has remained well since and has a normal quality of life. She is able to care for her children, walk up two flights of stairs and occasionally go out dancing in the evenings. (Eurekalert)

This is a rather remarkable case report. We are now in the era of bioengineered tissues. Exactly where this will lead us we don't know, but the field seems to be moving with remarkable rapidity. It again raises the idea that tissues might be made in laboratory flasks not only for medical uses but for food.

But that's another, and surprisingly controversial, subject (we've discussed it a couple of times and it always gets a very negative reaction).

More like this

This is a very exciting result to an ambitious operation, and it's no surprise that it was in all the newspapers here in the UK yesterday.

Over at Pro-Test we've taken a look at the pre-clinical work behind this study…

It's taken many years and a lot of work, but I'll bet that Ms.Castillo is pleased that the researchers kept at it.

One thing I do wonder is whether there is enough donated tissue available to make this procedure an option in many countries. It's notable that Spain operates a policy of presumed consent for organ donation, and while relatives of the deceased still have the final say it's created a culture where Spain has the highest level of organ donation in Europe. I tissue engineering is to be more widely used I suspect that synthetic scaffolds may by required.

By Paul Browne (not verified) on 20 Nov 2008 #permalink

Once the donor trachea was denuded of cells, did it matter whether the remaining scaffold was human in origin (aside from the presumably more natural shape)?

I assume it does matter, given references to Spain's policy on organ donation, but would a pig trachea have worked?

That's a good point. Implants made from non-human extracellular matrix have been used in other parts of the body (e.g.…), but as the authors of the Lancet paper point out the respiratory tract does contain more active immune system cells than most other organs, so avoiding any immune response was vital. Their method described in the Lancet paper didn't completely remove all chondrocyte cells but appears to have removed most of the antigens that could trigger an immune response.

I think that it should be possible to use ECM from non-human species for this purpose, though the processes used to remove cells and antigens will probably need further improvement.

By Paul Browne (not verified) on 20 Nov 2008 #permalink

I must say, I was certainly taken aback by the comment that "We are now in the ear of bioengineered tissues." Were you saying that bioengineered tissues would form a gigantic ear that would envelop us? Perhaps this is some sort of metaphor unique to your linguistic group, similar to being "under the thumb" or "ground underfoot"? Or is this the dawn of bioenginearing?

Aw, jeez, it's just a typo. There went all my fun.

By Chris Crawford (not verified) on 20 Nov 2008 #permalink

If revere had read the University of Bristol's press release properly, they would have seen that there IS a paper about this study, published in the LANCET on Tuesday. Hence the press release.