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Scientists report success growing cartilage to reconstruct nostrils and implanting tissue-engineered vaginal organs into humans
09 April 2014
Two new articles published in The Lancet report the first ever successful operations in humans to reconstruct the alar wings of the nose (nostrils) (Martin et al), and to implant tissue-engineered vaginal organs in women with a rare syndrome that causes the vagina to be underdeveloped or absent (Atala et al), in both cases using the patients’ own tissue.
In one paper, led by Professor Ivan Martin from the University of Basel in Switzerland, scientists report having engineered a human cartilage graft from patients’ own nasal septum cartilage cells to successfully rebuild the nostrils (alar lobule) of five individuals whose noses were damaged by skin cancer. One year after reconstruction, all five recipients were satisfied with their ability to breathe, as well as the cosmetic appearance of their nose, and did not report any local or systemic adverse events.
The nose is the most common site of non-melanoma skin cancer, because of its cumulative exposure to sunlight, with the highest frequency of cancer occurring on the alar lobule. Currently, when removing skin cancers, surgeons often have to cut away parts of cartilage, (for instance from the nasal septum, ear, or rib) as grafts to functionally reconstruct the tumour excision site. However, this painful and invasive procedure involves major additional surgery, and has been associated with complications at the site from which cartilage has been removed.
A team from the University of Basel, Switzerland, investigated an alternative approach using engineered cartilage tissue grown from patients’ own cells. They extracted the cartilage cells (chondrocytes) from the nasal septum of each patient, and multiplied the cells by exposing them to growth factors for two weeks. The expanded cells were seeded onto collagen membranes and cultured for two additional weeks, generating cartilage 40 times larger than the original biopsy. When the engineered grafts were ready they were shaped according to the defect and implanted.
According to Professor Martin, “The engineered cartilage had clinical results comparable to the gold standard cartilage graft surgery. This new technique could help the body accept the new tissue more easily, and improve the stability and functionality of the nostril. Our success is based on the long-standing, effective integration in Basel between our experimental group at the Department of Biomedicine and the surgical disciplines. It opens the way to using this engineered cartilage for more challenging reconstructions in facial surgery such as the complete nose, eyelid, or ear. The same engineered grafts are currently being tested in a parallel study for articular cartilage repair in the knee. Despite this optimism, the use of these procedures in the routine clinical practice is still rather distant, as it requires rigorous assessment of efficacy on larger cohorts of patients, and the development of business models and manufacturing paradigms that will guarantee cost-effectiveness.”*
In another Article, a team of scientists in the US and Mexico, led by Professor Anthony Atala from Wake Forest School of Medicine, USA, report on the long-term success of tissue-engineered vaginal organs implanted in four women, aged 13–18 years, with a condition known as Mayer-Rokitansky-Küster-Hauser syndrome that causes the vagina to be underdeveloped or absent. Eight years after transplantation, the organs continue to function as if they were native tissue and all recipients are sexually active, report no pain, and are satisfied with their desire/arousal, lubrication, and orgasm.
The team obtained a vulvar tissue biopsy from each patient from which they grew smooth muscle cells and vaginal epithelial cells in the lab. The cells were then placed onto specially designed vagina-shaped biodegradeable scaffolds and left to grow for 7 days. The researchers then surgically implanted the engineered vaginas, which remain structurally and functionally normal 8 years on.
According to Professor Atala, “Yearly tissue biopsy samples show that the reconstructed tissue is histologically and functionally similar to normal vaginal tissue. This technique is a viable option for vaginal reconstruction and has several advantages over current reconstructive methods because only a small biopsy of tissue is required, and using vaginal cells may reduce complications that arise from using non-vaginal tissue (eg, segments of large intestine or skin) such as infection and graft shrinkage.”*
According to Professor Martin Birchall, of UCL Ear Institute, London, UK, author of a Comment linked to both studies, “These authors have not only successfully treated several patients with a difficult clinical problem, but addressed some of the most important questions facing translation of tissue engineering technologies. The steps between first-in-human experiences such as those reported here and their use in routine clinical care remain many, including larger trials with long-term follow-up, the development of clinical grade processing, scale-out, and commercialisation. However, these hurdles are common to all potentially disruptive technologies, and many countries now have large translational income streams, engaged biotech companies and streamlined regulatory processes that may reduce the time to routine use significantly.”*
* Quotes direct from authors and cannot be found in text of Article / Comment