Cell Magnetic Targeting System for Repair of Severe Chronic Osteochondral Defect in a Rabbit Model

Abstract

The aim of this study was to investigate a cell delivery system for repair of severe chronic osteochondral defects using magnetically labeled mesenchymal stem cells (m-MSCs), with the aid of an external magnetic device, through the accumulation of a small number of m-MSCs into a desired area and to detect the suitable number of autologous m-MSCs needed for repair of the defect. Twenty-six male Japanese white rabbits aged 6 months were used. An osteochondral defect was created bilaterally at the weight-bearing surface of the medial femoral condyle of the rabbits' knees (3 mm diameter; 4 mm depth). At 4 weeks after creation of the defect, autogenic transplantation of the m-MSCs into the defect area was performed, followed by 10-min exposure to an external magnetic device, where animals were divided into four groups: high (1 × 10 6 m-MSCs), medium (2 × 10 5 m-MSCs), low (4 × 10 4 m-MSCs), and control (PBS injection). At 4 and 12 weeks posttransplantation of m-MSCs, repaired tissue was assessed histologically using the Fortier score with toluidine blue staining. Transplantation of a low number of m-MSCs was not enough to improve osteogenesis and chondrogenesis, but the medium and high groups improved repair of the chronic defect with chondrogenic tissues and showed histologically significantly better results than the control and low groups. The use of a magnetic targeting system for delivering m-MSCs has the potential to overcome the clinical hurdles for repair of the severe chronic osteochondral defect. Furthermore, this system is predicted to produce good clinical outcomes for humans, not only to repair osteochondral defects but also to repair a variety of damaged tissues.

Adaptive Materials Based on Iron Oxide Nanoparticles for Bone Regeneration

“…This technique significantly facilitated the infiltration of ferumoxide‐labelled cells into porous hydroxyapatite ceramic implanted in a rabbit ulnar defect and significantly contributed to the enhancement of bone formation even in the chronic phase. In another study, a magnetic targeting system for repair of severe chronic osteochondral defects using magnetically labeled mesenchymal stem cells (MSCs), with the aid of an external magnetic device, was investigated . Complete repair of the severe chronic defect including cartilage and subchondral bone was confirmed with transplantation of 2×10 5 MSCs.…”

Magnetic targeting as a strategy to enhance therapeutic effects of mesenchymal stromal cells

“…MT of MSCs has been trialed most often for the repair of articular cartilages which have limited healing potential [10, 24] (Table 1). Intra-articular MSC injections into cartilage defect regions resulted in poor engraftment, suggesting the need for inoculation of additional cell volumes.…”

A Magnetically Actuated Microscaffold Containing Mesenchymal Stem Cells for Articular Cartilage Repair

“…To overcome the shortcomings of cell‐based cartilage repair, cells, or scaffolds with the capability of magnetic actuation have been studied for active targeting and fixation to the lesions . For cells or scaffolds with magnetic behavior, magnetic nanoparticles (MNPs) under 50 nm were adopted, where MNPs have high effective surface areas for easier attachment of ligands and can label specific biomolecules or living cells .…”

“…However, the proposed MNP‐loaded cells or scaffolds can have drawbacks, such as inaccurate targeting by the control limit of the external magnetic field generation system or invasive surgery from the transplantation of the magnetic generation device. For example, Mahmoud et al proposed MNP‐loaded MSCs, which were guided to medial patella lesions in a rabbit model using external magnetic fields generated in a superconducting magnet system . However, because the MSCs are propelled along only one magnet orientation, it is difficult for them to be accurately guided to cartilaginous defects located in the patellofemoral groove.…”