Tissue engineering: Crocheting with cells

20. October 2014

Biotechnologists in the fast lane: articular cartilage, nostrils or a new vagina – tissue cultures make it possible. Researchers have even managed to create organs in the bioreactor using the body's own cells. Does its application stand at the threshold of being a clinically routine one?

A case in point: until now, patients with infiltrative, destructively growing basaliomas had been dealt a bad card. In order to completely remove the tumour, surgeons have had to, for example, extract parts of the nasal cartilage together with healthy tissue. For reconstruction they remove grafts from the nasal septum, from an ear or a rib. It’s not always possible to avoid complications at the donor site. The solution: Swiss researchers have now shown the potential already existing today in tissue engineering.

Always follow the nose

Professor Dr. Ivan Martin of the Department of Biomedicine at the University and University Hospital Basel tested a new technique in the clinic. He treated five patients from 76-88 years of age whose nostrils, due to tumour resections, were so badly damaged that a reconstruction was deemed necessary. Researchers isolated chondrocytes from biopsies and propagated these via cell culture. After two weeks there stood before them a 40-fold larger cell mass available for their use. Ivan Martin laid out cartilage onto collagen membranes and allowed it to grow for two weeks. Having been perfectly cut to fit, surgeons transplanted the new tissue. After completion of the study, all recipients were satisfied with both their nasal breathing function as well as with their appearance. No significant complications were observed. Martin now hopes by using the new method to close larger lesions of the ear or nose.

New vagina out of cell culture

Surgeons from Mexico and North Carolina faced other challenges. Their patients, aged 13-18 years, suffered from Mayer-von Rokitansky-Küster-Hauser syndrome. Due to a chromosomal defect a channelling of the genital strand failed to materialise during embryonic development. Victims suffer from hypoplasia or complete aplasia of the vagina and uterus. Until now, doctors have had to perform complicated reconstructions using skin grafts or intestinal loops. Director of studies Atlántida M. Raya-Rivera has now employed methods of tissue engineering here – with success. In order to construct a vagina from cells of each patient, doctors extracted muscle and epithelial cells and anchored these onto substrates. One side consisted of muscle cells, on the other side there were epithelial cells. After propagation in vitro surgeon formed a tube and implanted the construct. Over the next few months a vagina formed, made of muscles, mucous membrane, nerves and blood vessels. After six months, the original vehicle substrate had completely dissolved. Over subsequent years, a functional vagina emerged, something which Raya-Rivera ascertained through the Female Sex Function Index.

Help for the knee

Researchers however have not allowed themselves to just be satisfied with that. Their goal for a long time has been to grow tissue for orthopaedic applications. Chondrocytes from the nasal septum would be an interesting base material because they regenerate themselves, in contrast to articular cartilage. Professor Ivan Martin refers to respective differences originating in the Hox genes. Yet the differences don’t end there: tissue of the nose is derived from the neuroectoderm whereas the articular cartilage originates from the mesoderm. In addition, there exist biophysical differences. In the clinic however, the differences are not relevant. Researchers isolated chondrocytes from the nose and multiplied them in vitro. In goats, the cells adapted to their new environment in the joint. Whether this will work in humans or not should soon be indicated by a study involving 25 patients. Doctors are planning MRI controls postoperatively after six, twelve and 24 months – results are not yet available.

Meniscus in distress

Much longer strides have been made in the treatment of patients having had a meniscectomy. After success in animal studies, C. Thomas Vangsness from the University of Southern California wanted to know which clinical benefits mesenchymal stem cells might have. He took 55 volunteers, from whom at least 50 percent of the medial meniscus had been removed, into a randomised double-blind study. Within seven days of the partial meniscectomy Vangness injected either 50 or 150 million allogeneic stem cells into the synovial bursa. The solution also contained electrolytes, hyaluronic acid and albumin. Dissolved hyaluronic acid was used as a control. Despite their being methodological weaknesses in quantitative MRI, there was evidence that stem cells lead to a significantly higher volume of meniscus. In the follow-up done after two years, patients of the “high-dose group” also had significantly better scores on the Lysholm Knee Scoring Scale. Clinically significant complications did not occur.

Muscles as needed

For orthopaedic surgeons it’s not only cartilage that is of interest. Scientists at the Max Delbrück Centre for Molecular Medicine (MDC) and the Berlin Charité (Germany) have now achieved a major breakthrough in repairing muscle damage. Until now, all attempts to use stem cells had failed. Dr. Andreas Marg and Professor Dr. Simone Spuler report on a new method. They received tissue samples from the thigh muscles of volunteer donors between 20 and 80 years of age. Spuler cultured muscle fibre fragments under conditions of oxygen deprivation at four degrees Celsius. Under these conditions only the satellite cells multiplied, ie muscle stem cells, but not the connective tissue cells. The team then transplanted muscle fragments into tibial muscles of mice – with success: the desired regeneration occurred. Further studies are necessary here in order to explore clinical potential.



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