Now for a guest entry by Pro-Test member, Bianca Summons:
Many years of research have today culminated in what could arguably be deemed an historic medical event. Claudia Castillo, a Columbian woman aged 30 who now lives in Spain, has been pronounced ‘in excellent health’ five months after a significant tissue-engineering operation following irreparable damage from tuberculosis.
As a result of a long line of experiments using pigs, cows, dogs, rats and sheep during the 1990s, Spanish doctors were able to work with researchers in Bristol to decellularise a donor trachea from a 51-year-old woman and successfully implant it into Ms Castillo. Decellularisation is needed in order to ensure that the receiver’s body does not reject the transplanted organ: however, this must not take place to such a degree that the integrity of the donor organ’s structure is compromised negatively. Significantly, the donor trachea was repopulated with Ms Castillo’s own stem cells, rather than xenogeneically- or allogeneically-produced cells being used, and unlike other transplant patients, Ms Castillo will not have to take immunosuppressants as part of her post-operative care (a positive, given how far immunosuppressants can leave patients vulnerable to infection), as her body recognises her own cells. The other option for Ms Castillo would have been to have a lung removed, which could potentially have shortened her life.
The findings of the research, published in The Lancet (1), describe how the decellularised donated trachea was rotated in a bioreactor with Ms Castillo’s stem cells before transplantation. The donor trachea, after time in the bioreactor, looked identical to a normal trachea, and some time after the operation had taken place, the divisions between Ms Castillo’s own trachea and the donated trachea could barely be seen.
In their Lancet article Prof. Macchiarini and his team discuss the research that lead to the development of a bioengineered trachea that could be transplanted into their patient. The trachea is particularly rich in active immune cells due to the need to defend the body against inhaled germs, which makes it a difficult organ for transplant surgery.
Prof. Macchiarini will describe the role of animal research in this work in detail in a forthcoming paper in the Journal of Thoracic and Cardiovascular Surgery, but in the Lancet paper (1) he provides a short summary of the work:
Tissue bioengineering already has provided functional human organ replacements elsewhere. Previous preclinical airway experiments have been too lengthy and complex for routine clinical application, or relied on non-biological matrices. We have used mouse and pig models to develop a streamlined process in which autologous epithelial and mesenchymal stem-cell-derived chondrocytes are seeded onto a decellularised donor tracheal scaffold and matured in a novel bioreactor system. Encouraged by the in-vitro generation of short but vital tracheal matrices and by the absence of an immunological response to allografted and xenografted tracheal constructs in animals, we aimed to bioengineer tubular tracheal matrices longer than 6 cm, and to assess the application of this technology in a patient with end-stage airway disease”
Clearly animal research was integral to this advance as it is to the field of tissue engineering in general.
It’s not just European scientists who are advancing the science of tissue engineering, US scientists such as Joseph Vacanti of the Harvard Stem Cell Institute have been involved in the field of tissue engineering since its birth in the 1980’s and continue to lead the field to this day. Indeed it was an experiment in 1997 where Dr. Vacanti used a synthetic polymer scaffold seeded with cartilage cells to grow cartilage in the shape of a human ear on the back of a mouse that first brought the field of tissue engineering to the attention of the wider public, though some very inaccurate reporting at the time didn’t help when it came to appreciating of the significance of Dr. Vacanti’s work. Hopefully last weeks announcement will show the public what the work of scientists such as Prof. Macchiarini and Dr. Vacanti is really about.
Animal research in Europe over the past ten years showed extremely positive results in both pigs and dogs, and Ms Castillo is the first human in which the same techniques have been applied. The success of her treatment allows enormous progression both in terms of transplant development and in terms of the use of extra-cellular matrices.
Regards
Bianca Summons, Pro-Test
Addendum: The paper in the Journal of Thoracic and Cardiovascular Surgery by Prof. Macchiarini and colleagues describing the animal research that led to this surgery has been published and can be read here.
(1) Macchiarini, P. et al., “Clinical Transplantation of a tissue-engineered airway”, The Lancet, Online Publication 19th November 2008
