Articular cartilage repair using an intra‐articular magnet and synovium‐derived cells

Abstract

The purpose of this study was to investigate the chondrogenic potential of magnetically labeled synovium-derived cells (M-SDCs) and examine whether M-SDCs could repair the articular cartilage using an intra-articular magnet after delivery to the lesion. Synovium-derived cells (SDCs) were cultured from the synovium of a rat knee, and were magnetically labeled with ferumoxides. M-SDCs were examined with a transmission electron microscope. A pellet culture system was used to evaluate the chondrogenic potential of M-SDCs in a magnetic field. In a rat model, allogeneic M-SDCs were injected into the knee after we made an osteochondral defect on the patellar groove and implanted an intra-articular magnet at the bottom of the defect. We histologically examined the defects at 48 h, 4 weeks, 8 weeks, and 12 weeks after treatment. Electron microscopy showed the transfection of ferumoxides into SDCs. The pellet cultures revealed the chondrogenic potential of M-SDCs in a magnetic field. M-SDCs accumulated in the osteochondral defect at 48 h after treatment, and we confirmed the regeneration of the articular cartilage at 4 weeks, 8 weeks, and 12 weeks after treatment using an intra-articular magnet. We demonstrated that articular cartilage defects could be repaired using an intra-articular magnet and M-SDCs. We believe that this system will be useful to repair human articular cartilage defects. Keywords: cell delivery system; magnet; synovium; intra-articular injection; cartilage repair Articular cartilage is well known to have very limited self-healing potential. There are many procedures, including drilling, abrasion, microfracture, and distraction, for repairing the articular cartilage.1-7 However, the defects are repaired by fibrous tissues during those procedures, 6,8 and a routine procedure for articular cartilage defect repair has not yet been established.Currently, engineered cartilage tissues are in widespread clinical use, and good clinical results have been achieved with these tissues.9,10 However, this procedure requires the harvesting of a small amount of cartilage tissues from the patient prior to cartilage transplantation. It is therefore necessary to implement a lessinvasive procedure.Recently, synovium-derived cells (SDCs) have been found to have a high potential for both proliferation and differentiation.11-15 Synovial tissues are easy to harvest and may be collected from any joint without damaging the articular cartilage. We therefore evaluated the method of transplanting SDCs for repairing articular cartilage defects.Previous studies have suggested that intra-articular injected mesenchymal stem cells (MSCs) mobilize to the injured tissues. 16 This transplantation was less invasive, but was inefficient because the injected cells spread throughout the joint space. Consequently, we created an intra-articular magnet which had a strong magnetic force, for efficient transplantation. The delivered cells were magnetically labeled with ferumoxides, which is approved by the United States Food and Drug Admi...

Synovia-Derived Mesenchymal Stem Cell Application in Musculoskeletal Injuries: A Review

“…The unique matrix structure, rich in collagen fibers, proteoglycans, and interstitial fiber, provides a viscoelastic environment that allows the AC to support its biomechanical functions [8]. It has been well established that the AC has limited self-healing capacities [3][4][5][7][8][9][10][11][12][13][14][15] due to its intrinsic characteristics, namely its avascular nature, limited number of resident stem cells, and unique matrix organization [4]. Partial defects on mature cartilage do not heal spontaneously.…”

“…Surgical procedures that stimulate the bone marrow (BM), such as abrasion, distraction, drilling, and microfractures, are said to promote chondrogenesis phenomena, by inducing the BM mesenchymal stem cells (MSCs) from the subchondral bone. However, in most cases, these techniques lead to the formation of fibrocartilaginous tissue, instead of hyaline cartilage, probably due to an overloading of the BM and a small number of MSCs available, and the repaired cartilage often degenerates in the long term [3][4][5]11]. Alternative regenerative approaches, regarding cartilage tissue engineering, are being developed, in order to overcome these disadvantages.…”

“…They present a high self-renewal ability [31,40], superior potential for chondrogenic differentiation [3,4,10,12,30,32,37], and a high proliferative capacity [3,4,10,12,29,32,37,40], both compared to nonjoint (bone marrow, adipose tissue, and umbilical cord) and joint tissues (AC and synovial fluid) [4]. SM-MSCs have been successfully differentiated into osteogenesis, chondrogenesis, and adipogenesis [31,35], as well as toward myogenesis, but at a minor extent.…”

“…The SM is easy to harvest [40] and can be collected from any joint, without impairing the AC tissue [3]. It can be obtained arthroscopically, with a minor degree of invasiveness [10] through a small biopsy [31] and with minor complications at the donor site [12].…”

“…In osteoarticular and skeletal muscle clinical injuries, tissue self-healing mechanisms are often insufficient and associated to scar tissue formation and long-term healing processes [2][3][4][5]. Different treatment techniques have been developed in the past years, but until now, no ideal regenerative treatment approach has yet been established [2,4].…”