Patricia Anne Erillo BN4B

EENT Update

Cartilage Repair Advances by a Nose

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
th 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.e sites of septum
cartilage biopsy.

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.

"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.

Sources:

https://www.medscape.com/viewarticle/870800