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Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial.
Lancet 2016; 388(10055):1985-1994Lct

Abstract

BACKGROUND

Articular cartilage injuries have poor repair capacity, leading to progressive joint damage, and cannot be restored predictably by either conventional treatments or advanced therapies based on implantation of articular chondrocytes. 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. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects.

METHODS

In a first-in-human trial, ten patients with symptomatic, post-traumatic, full-thickness cartilage lesions (2-6 cm2) on the femoral condyle or trochlea were treated at University Hospital Basel in Switzerland. Chondrocytes isolated from a 6 mm nasal septum biopsy specimen were expanded and cultured onto collagen membranes to engineer cartilage grafts (30 × 40 × 2 mm). The engineered tissues were implanted into the femoral defects via mini-arthrotomy and assessed up to 24 months after surgery. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes included self-assessed clinical scores and MRI-based estimation of morphological and compositional quality of the repair tissue. This study is registered with ClinicalTrials.gov, number NCT01605201. The study is ongoing, with an approved extension to 25 patients.

FINDINGS

For every patient, it was feasible to manufacture cartilaginous grafts with nasal chondrocytes embedded in an extracellular matrix rich in glycosaminoglycan and type II collagen. Engineered tissues were stable through handling with forceps and could be secured in the injured joints. No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months after surgery. Radiological assessments indicated variable degrees of defect filling and development of repair tissue approaching the composition of native cartilage.

INTERPRETATION

Hyaline-like cartilage tissues, engineered from autologous nasal chondrocytes, can be used clinically for repair of articular cartilage defects in the knee. Future studies are warranted to assess efficacy in large controlled trials and to investigate an extension of indications to early degenerative states or to other joints.

FUNDING

Deutsche Arthrose-Hilfe.

Authors+Show Affiliations

Department of Surgery and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.Department of Surgery and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.Department of Surgery and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.Department of Surgery and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.Department of Surgery and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.Department of Surgery and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.Department of Surgery and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.Department of Institute of Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.Department of Radiology, University Hospital Basel, University of Basel, Basel, Switzerland.Department of Radiology, University Hospital Basel, University of Basel, Basel, Switzerland.Department of Surgery and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.Department of Surgery and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.Department of Surgery and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.Department of Surgery and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland. Electronic address: ivan.martin@usb.ch.Department of Surgery and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.

Pub Type(s)

Journal Article
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27789021

Citation

Mumme, Marcus, et al. "Nasal Chondrocyte-based Engineered Autologous Cartilage Tissue for Repair of Articular Cartilage Defects: an Observational First-in-human Trial." Lancet (London, England), vol. 388, no. 10055, 2016, pp. 1985-1994.
Mumme M, Barbero A, Miot S, et al. Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial. Lancet. 2016;388(10055):1985-1994.
Mumme, M., Barbero, A., Miot, S., Wixmerten, A., Feliciano, S., Wolf, F., ... Jakob, M. (2016). Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial. Lancet (London, England), 388(10055), pp. 1985-1994. doi:10.1016/S0140-6736(16)31658-0.
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 PMID: 27789021.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial. AU - Mumme,Marcus, AU - Barbero,Andrea, AU - Miot,Sylvie, AU - Wixmerten,Anke, AU - Feliciano,Sandra, AU - Wolf,Francine, AU - Asnaghi,Adelaide M, AU - Baumhoer,Daniel, AU - Bieri,Oliver, AU - Kretzschmar,Martin, AU - Pagenstert,Geert, AU - Haug,Martin, AU - Schaefer,Dirk J, AU - Martin,Ivan, AU - Jakob,Marcel, PY - 2016/08/16/received PY - 2016/08/24/revised PY - 2016/08/25/accepted PY - 2016/10/30/pubmed PY - 2016/11/11/medline PY - 2016/10/30/entrez SP - 1985 EP - 1994 JF - Lancet (London, England) JO - Lancet VL - 388 IS - 10055 N2 - BACKGROUND: Articular cartilage injuries have poor repair capacity, leading to progressive joint damage, and cannot be restored predictably by either conventional treatments or advanced therapies based on implantation of articular chondrocytes. 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. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects. METHODS: In a first-in-human trial, ten patients with symptomatic, post-traumatic, full-thickness cartilage lesions (2-6 cm2) on the femoral condyle or trochlea were treated at University Hospital Basel in Switzerland. Chondrocytes isolated from a 6 mm nasal septum biopsy specimen were expanded and cultured onto collagen membranes to engineer cartilage grafts (30 × 40 × 2 mm). The engineered tissues were implanted into the femoral defects via mini-arthrotomy and assessed up to 24 months after surgery. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes included self-assessed clinical scores and MRI-based estimation of morphological and compositional quality of the repair tissue. This study is registered with ClinicalTrials.gov, number NCT01605201. The study is ongoing, with an approved extension to 25 patients. FINDINGS: For every patient, it was feasible to manufacture cartilaginous grafts with nasal chondrocytes embedded in an extracellular matrix rich in glycosaminoglycan and type II collagen. Engineered tissues were stable through handling with forceps and could be secured in the injured joints. No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months after surgery. Radiological assessments indicated variable degrees of defect filling and development of repair tissue approaching the composition of native cartilage. INTERPRETATION: Hyaline-like cartilage tissues, engineered from autologous nasal chondrocytes, can be used clinically for repair of articular cartilage defects in the knee. Future studies are warranted to assess efficacy in large controlled trials and to investigate an extension of indications to early degenerative states or to other joints. FUNDING: Deutsche Arthrose-Hilfe. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/27789021/Nasal_chondrocyte_based_engineered_autologous_cartilage_tissue_for_repair_of_articular_cartilage_defects:_an_observational_first_in_human_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(16)31658-0 DB - PRIME DP - Unbound Medicine ER -