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Arthroscopic, histological and MRI analyses of cartilage repair after a minimally invasive method of transplantation of allogeneic synovial mesenchymal stromal cells into cartilage defects in pigs.

ABSTRACT: Transplantation of synovial mesenchymal stromal cells (MSCs) may induce repair of cartilage defects. We transplanted synovial MSCs into cartilage defects using a simple method and investigated its usefulness and repair process in a pig model.The chondrogenic potential of the porcine MSCs was compared in vitro. Cartilage defects were created in both knees of seven pigs, and divided into MSCs treated and non-treated control knees. Synovial MSCs were injected into the defect, and the knee was kept immobilized for 10 min before wound closure. To visualize the actual delivery and adhesion of the cells, fluorescence-labeled synovial MSCs from transgenic green fluorescent protein (GFP) pig were injected into the defect in a subgroup of two pigs. In these two animals, the wounds were closed before MSCs were injected and observed for 10 min under arthroscopic control. The defects were analyzed sequentially arthroscopically, histologically and by magnetic resonance imaging (MRI) for 3 months.Synovial MSCs had a higher chondrogenic potential in vitro than the other MSCs examined. Arthroscopic observations showed adhesion of synovial MSCs and membrane formation on the cartilage defects before cartilage repair. Quantification analyses for arthroscopy, histology and MRI revealed a better outcome in the MSC-treated knees than in the non-treated control knees.Leaving a synovial MSC suspension in cartilage defects for 10 min made it possible for cells to adhere in the defect in a porcine cartilage defect model. The cartilage defect was first covered with membrane, then the cartilage matrix emerged after transplantation of synovial MSCs.

SUBMITTER: Nakamura T

PROVIDER: S-EPMC3296518 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Arthroscopic, histological and MRI analyses of cartilage repair after a minimally invasive method of transplantation of allogeneic synovial mesenchymal stromal cells into cartilage defects in pigs.

Nakamura Tomomasa T Sekiya Ichiro I Muneta Takeshi T Hatsushika Daisuke D Horie Masafumi M Tsuji Kunikazu K Kawarasaki Tatsuo T Watanabe Atsuya A Hishikawa Shuji S Fujimoto Yasuhiro Y Tanaka Hozumi H Kobayashi Eiji E

Cytotherapy 20120301 3

<h4>Background aims</h4>Transplantation of synovial mesenchymal stromal cells (MSCs) may induce repair of cartilage defects. We transplanted synovial MSCs into cartilage defects using a simple method and investigated its usefulness and repair process in a pig model.<h4>Methods</h4>The chondrogenic potential of the porcine MSCs was compared in vitro. Cartilage defects were created in both knees of seven pigs, and divided into MSCs treated and non-treated control knees. Synovial MSCs were injected ...[more]

PMID: 22309371

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Project description:BackgroundFocal lesions to the articular cartilage in the knee might have demolishing consequences to the knee. There exists a wide range of possible surgical procedures targeting these injuries, however no significant differences have been found between these procedures. This may support that the improvement is a result of rehabilitation, and not the surgery itself. Arthroscopic microfracture (MF) treatment has gained popularity, and has become the treatment of choice in patients with knee cartilage defects globally. In this study we want to increase knowledge, both clinical and economic, about arthroscopic microfracture (AF) compared to arthroscopic debridement (AD) and physical rehabilitation both in the short run, and in the long run.Methods/designTo compare arthroscopic microfracture with arthroscopic debridement and physiotherapy for the treatment of focal cartilage lesions in the knee, a long-term, double-blinded, randomized controlled multicenter trial will be conducted. A total of 114 men and non-pregnant women with a symptomatic focal full thickness cartilage lesion in the knee less than 2 cm2 will be included in the study. The two treatment allocations will receive identical rehabilitation, which is made up of 3 phases: accommodation, rehabilitation and return to activity. Follow up is 24 months, where all will be invited to participate in late follow ups after 5 and 10 years. The Knee Injury and Osteoarthritis Outcome Score (KOOS) knee-related quality of life (QoL) subscore is the primary endpoint. Clinical parameters, questionnaires and radiologic modalities (Magnetic Resonance Imaging (MRI) and x-ray) will be used as secondary endpoints.DiscussionThis is an ongoing multicenter study with a high level of evidence to compare arthroscopic microfracture with arthroscopic debridement and physiotherapy for the treatment of isolated symptomatic full thickness cartilage lesions in the knee joint.Trial registrationClinicalTrials.gov ID: NCT02637505 (December 15, 2015).

Project description:Advanced tools for the in situ treatment of articular cartilage lesions are attracting a growing interest in both surgery and bioengineering communities. The interest is particularly high concerning the delivery of cell-laden hydrogels. The tools currently available in the state-of-the-art hardly find an effective compromise between treatment accuracy and invasiveness. This paper presents a novel arthroscopic device provided with a bendable tip for the controlled extrusion of cell-laden hydrogels. The device consists of a handheld extruder and a supply unit that allows the extrusion of hydrogels. The extruder is equipped with a disposable, bendable nitinol tip (diameter: 4 mm, length: 92 mm, maximum bending angle: 90°) that guarantees access to hard-to-reach areas of the joint, which are difficult to get to, with conventional arthroscopic instruments. The tip accommodates a biocompatible polymer tube that is directly connected to the cartridge containing the hydrogel, whose plunger is actuated by a volumetric or pneumatic supply unit (both tested, in this study). Three different chondrocyte-laden hydrogels (RGD-modified Vitrogel®, methacrylated gellan gum, and an alginate-gelatine blend) were considered. First, the performance of the device in terms of resolution in hydrogel delivery was assessed, finding values in the range between 4 and 102 µL, with better performance found for the pneumatic supply unit and no significant differences between straight tip and bent tip conditions. Finite element simulations suggested that the shear stresses and pressure levels generated during the extrusion process were compatible with a safe deposition of the hydrogels. Biological analyses confirmed a high chondrocyte viability over a 7-day period after the extrusion of the three cell-laden hydrogel types, with no differences between the two supply units. The arthroscopic device was finally tested ex vivo by nine orthopedic surgeons on human cadaver knees. The device allowed surgeons to easily deliver hydrogels even in hard-to-reach cartilage areas. The outcomes of a questionnaire completed by the surgeons demonstrated a high usability of the device, with an overall preference for the pneumatic supply unit. Our findings provide evidence supporting the future arthroscopic device translation in pre-clinical and clinical scenarios, dealing with osteoarticular treatments.

Dataset Information

Arthroscopic, histological and MRI analyses of cartilage repair after a minimally invasive method of transplantation of allogeneic synovial mesenchymal stromal cells into cartilage defects in pigs.

Publications

Arthroscopic, histological and MRI analyses of cartilage repair after a minimally invasive method of transplantation of allogeneic synovial mesenchymal stromal cells into cartilage defects in pigs.

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