Abstract
Cartilage regeneration treatments using stem cells are associated with problems due to the cell source and the difficulty of delivering the cells to the cartilage defect. We consider labeled induced pluripotent stem (iPS) cells to be an ideal source of cells for tissue regeneration, and if iPS cells could be delivered only into cartilage defects, it would be possible to repair articular cartilage. Consequently, we investigated the effect of magnetically labeled iPS (m-iPS) cells delivered into an osteochondral defect by magnetic field on the repair of articular cartilage. iPS cells were labeled magnetically and assessed for maintenance of pluripotency by their ability to form embryoid bodies in vitro and to form teratomas when injected subcutaneously into nude rats. These cells were delivered specifically into cartilage defects in nude rats using a magnetic field. The samples were graded according to the histologic grading score for cartilage regeneration. m-iPS cells differentiated into three embryonic germ layers and formed teratomas in the subcutaneous tissue. The histologic grading score was significantly better in the treatment group compared to the control group. m-iPS cells maintained pluripotency, and the magnetic delivery system proved useful and safe for cartilage repair using iPS cells.
Highlights
Articular cartilage is known for its poor regenerative and reparative ability, making repair difficult after injury due to insults such as trauma, osteoarthritis, or rheumatoid arthritis
Cell counts revealed that m-induced pluripotent stem (iPS) cells made up 93.1 ± 2.2% of the population while non-miPS cells made up 6.9 ± 2.2% (P < 0001)
These findings suggest that they have the ability to differentiate into three embryonic germ layers and that magnetically labeled iPS (m-iPS) cells maintain pluripotency
Summary
Articular cartilage is known for its poor regenerative and reparative ability, making repair difficult after injury due to insults such as trauma, osteoarthritis, or rheumatoid arthritis. Current treatments for cartilage injury include conservative treatments such as rehabilitation, anti-inflammatory analgesic medication, and intra-articular injection or operative treatments such as bone marrow stimulating techniques (drilling and microfracture) and autologous osteochondral grafting [1, 2]. Bone marrow stimulating techniques and autologous osteochondral grafting are unable to completely restore hyaline cartilage. There have been many reports of cartilage regeneration treatment using stem cells. Reported studies on cartilage regeneration have used MSCs, as well as stem cells derived from adipose tissue, synovial tissue, and peripheral blood [4,5,6]. Vega and collaborators reported significantly better function and cartilage quality in osteoarthritis patients treated with MSCs by intra-articular injection [7]. Major disadvantages of MSCs include limitations in vitro proliferative potential, and their proliferative capacity and synthetic capacity decline with age [8]
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