Tissue engineered nasal cartilage for the regeneration of articular cartilage in the knee after traumatic injury

Although articular cartilage lesions are more common in older people due to degeneration, they also occur regularly in younger people e.g. due to accidents. Particularly in the case of larger defects, spontaneous healing is almost never observed and, if no adequate treatment is carried out, development of an arthrosis can finally occur, which may ultimately lead to full joint replacement. We proposed here the use of the same type of engineered cartilage grafts as described in the study above.

The aim of this phase I study is to treat patients with cartilage defects of 2-8cm2 in the knee (but not arthrosis) in order to demonstrate the safety and feasibility of this method of treatment and to collect initial results for efficacy.

Treatments for the repair of the cartilage have the potential to lessen the pain, to increase the quality of life and to prevent or delay the necessity of the joint replacement. However, today's strategies for healing these defects require long rehabilitation measures, are limited in terms of size of the injury, availability of donor tissue, and often lead to unsatisfactory clinical results due to the lower quality of the repair tissue. Persistent pain and a restricted mobility or function of the joint often remains after treatment. Even new therapies based on articular chondrocytes cannot reproducibly and permanently restore the cartilage function, although they mitigate the symptoms in the short term.

In a clinical phase I study with 18 patients at the University hospital Basel, funded by the Deutsche Arthrosehilfe, another autologous cell type (nasal cartilage cells), showing better and more donor-independent properties for cartilage regeneration, was used. In addition experiments in the lab and animals had shown that nasal chondrocytes not only react to mechanical forces in a similar way than articular chondrocytes, but also adapt to the environment in the knee and are more resistant to inflammatory conditions typical after operations. In addition a tissue instead of the cells was implanted which had a higher stability. The aim of this study is to treat patients with a deep cartilage defect of 2-8cm2 (but not arthrosis) in order to demonstrate the safety and feasibility of this method of treatment and to collect initial results for efficacy. The results have now been published in "The lancet". Both the engineering of the tissues as well as the study itself is subject to strict regulations and is monitored by the Swiss Agency for therapeutic products (Swissmedic) and the Ethics Commission.

In contrast to conventional cell therapies, in which the cells are implanted in the joint, in this study a cartilaginous tissue was engineered in the laboratory, which was intraoperatively trimmed according to the defect size before implantation. For the engineering of this tissue, a small piece of tissue (6 mm diameter) was removed from the nasal septum in an outpatient procedure and the cells were enzymatically isolated from the tissue. After a 2-week proliferation phase in the laboratory, the cells are seeded into a scaffold and form within 2 weeks a 30 ├Ś 40 mm-sized cartilage tissue.

After implantation, the patients (19-52 years) received rehabilitation (physiotherapy) and were examined after 2 and 6 weeks, as well as after 6, 12 and 24 months, to assess the clinical course of healing and the cartilage repair tissue. In addition to the clinical investigations, the follow-up examinations also included an MRI, which can be used to assess the stability as well as the quality of the tissue. Moreover, standardized questionnaires were used to determine the satisfaction of the patient with regard to pain, other symptoms, sports, quality of life and activities of daily live.

For all patients in the study, an implant could be successfully produced that displayed typical characteristics of cartilage tissue. After implantation, no undesirable transplant-associated side effects could be detected in any of the patients, demonstrating the safety and feasibility of the method. In the follow-up investigations it was also shown that a repair tissue had formed, which is very similar to the native cartilage. In the self-assessment of the patients, a relevant improvement in the symptoms could be seen.

Despite these promising results, the number of patients is too small to make a reliable statement about the efficacy.

Publication:

Mumme M et al. Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial. Lancet. 2016 Oct 22;388(10055):1985-1994. Pubmed.

Universit├Ąt Basel, Christian Flierl