Cartilage Repair Advances by a Nose

Janis C. Kelly

October 21, 2016

Cells from the nasal septum can be used to generate cartilage tissue grafts for knee repair, according to a proof-of-principle study that enrolled 10 patients.

The nasal chondrocyte grafts produced repair tissue "approaching the composition of native hyaline cartilage," and the repairs were more durable than those based on injections of cells taken from autologous joint cartilage, Marcus Mumme, MD, from the Department of Surgery and the Department of Biomedicine, University Hospital Basel, University of Basel, Switzerland, and colleagues report in an article published in the October 22 issue of the Lancet.

At 24 months after surgery, the cartilage tissue grafts were associated with significant improvements in all patients except one who had suffered a new injury to the same knee. The mean score for the International Knee Documentation Committee subjective patient evaluation of knee function improved from almost 60 to about 75 (P = .0305). The mean Knee Injury and Osteoarthritis Outcome Score for symptoms improved from about 65 to just over 80 (P = .0351). Similar improvements were seen in the Knee Injury and Osteoarthritis Outcome Score subdomains of pain, function in sport, activities of daily living, and quality of life.

The authors note that the increase in clinical scores was in the range of previously reported outcomes with articular chondrocyte approaches, but more durable; clinical improvements with nasal chondrocyte tissue implants did not fade between 6 and 24 months, as had been seen with the older procedure.

There were no adverse reactions during the 24 months after implantation, and no adverse reactions in the sites of septum cartilage biopsy.

Nasal Chondrocytes May Be Better for Repairs Than Articular Chondrocytes

This observational first-in-human study enrolled 10 patients aged 18 to 55 years with posttraumatic full-thickness cartilage injuries on the femoral condyle or trochlea of between 2 and 6 cm2. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes were patient satisfaction, morphological quality of repair tissue at 6 and 12 months, and compositional quality of repair tissue at 6 and 12 months.

The researchers turned to nasal chondrocytes in an attempt to improve on previous methods that used chondrocytes taken from healthy cartilage in the injured joint. "Compared with articular chondrocytes, chondrocytes derived from the nasal septum have superior and more reproducible capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment," the authors write.

The researchers harvested nasal chondrocytes from 6-mm-diameter punch biopsies of autologous septal cartilage. Plastic surgeons performed the minimally invasive biopsies, using local anaesthesia. After 4 weeks of expansion in culture, including seeding onto a collagen type I/III membrane, grafts were selected for implantation. Nasal chondrocytes maintained their chondrogenic properties even after extensive expansion in culture and were able to generate biochemically and biomechanically mature tissue grafts large enough to be clinically useful. The authors suggest this may help overcome some of the limitations associated with use of suspensions of undifferentiated cells or cell-seeded scaffolds.

Graft implantation was done via mini-arthrotomy, with the graft trimmed to fit into a cleaned-out cartilage lesion and fixed into place with absorbable sutures and fibrin glue

Be Careful With That Nose

Although the nasal septal cells are obtained in a relatively noninvasive manner, some caution is advised. "It is of utmost importance that cartilage is only harvested from the central part of the septum, with preservation of at least 1 cm of the caudal and dorsal septal struts. Otherwise, nasal shape and stability are at risk," surgeons Nicole Rotter, MD, and Rolf E. Brenner, MD, warn in a linked comment. "Potential adverse reactions at the harvest site—eg, septal deviations or disturbances of the nasal valve or external nasal shape—should be examined and reported with special care."

Dr Rotter is from the Department of Otorhinolaryngology, Head and Neck Surgery, Ulm University Medical Center, Germany. Dr Brenner is from the Department of Orthopaedics, Division for Biochemistry of Joint and Connective Tissue Diseases, University of Ulm, Germany.

At 24 Months, Patches Resembled Natural Cartilage

Histologically, the bioengineered implants developed into tissue that resembled natural cartilage. The grafts stained intensely for glycosaminoglycan and showed evidence of hyaline extracellular matrix, including high positivity for type II collagen in the high-glycosaminoglycan areas, with type I collagen mostly on the periphery. The level at which repair tissue filled the cartilage defects was variable, but the glycosaminoglycan content of the repair tissue increased from 6 to 24 months, indicating cartilage maturation.

The authors conclude that further studies with hyaline-like cartilage tissues engineered from autologous nasal chondrocytes are warranted in large controlled trials, as well as in early degenerative arthritis and in joints other than the knee.

Next up: NosetoKnee2

"Overall, this first-in-human trial represents an important advance towards less invasive, cell-based repair technologies for articular cartilage defects, because the site of tissue harvest is not located within the healthy part of a joint, avoiding potential side-effects of harvesting," Dr Rotter and Dr Brenner write.

"Our findings confirm the safety and feasibility of cartilage grafts engineered from nasal cells to repair damaged knee cartilage. But use of this procedure in everyday clinical practice is still a long way off as it requires rigorous assessment of efficacy in larger groups of patients and the development of manufacturing strategies to ensure cost effectiveness," lead author Ivan Martin, MD, professor of tissue engineering at the University of Basel and University Hospital Basel in Switzerland, said in a news statement. "Moreover, in order to extend the potential use of this technique to older people or those with degenerative cartilage pathologies like osteoarthritis, a lot more fundamental and pre-clinical research work needs to be done."

The upcoming NosetoKnee2 phase 2 multicenter, clinical study will compare the efficacy of an engineered cartilage transplant produced from nasal chondrocytes with a cell-activated matrix for the treatment of articular cartilage lesions in the knee.

The study was funded by Deutsche Arthrose-Hilfe. The authors and commentators have disclosed no relevant financial relationships.

Lancet. 2016;388:1957-1958, 1985-1994. Article abstract, Comment extract

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