Abstract
Cartilage is considered to be immune privileged in general. Clinically, live cells are removed from subcutaneously transplanted allogeneic cartilage mainly for preservation and for infection control. However, because maintaining cartilage feature requires live chondrocyte, it would be beneficial to subcutaneously transplant cartilage with live chondrocyte even if it was allogeneic. We harvested femoral head from 3-week-old male C57BL/6 mice, subcutaneously transplanted to 6-week-old male mice, BALB/c, BALB/c nu/nu, or C57BL/6-Tg (enhanced green fluorescent protein [EGFP] under the control of the CMV-IE enhancer, chicken beta-actin promoter, rabbit beta-globin genomic DNA [CAG promoter]), as allogeneic, allogeneic immunodeficient control, or syngeneic transplantation. We also transplanted cartilaginous particles from human induced pluripotent stem cells derived from human leukocyte antigen homozygous donor to 6-week-old male mice either BALB/c and BALB/c nu/nu as xenogeneic or xenogeneic immunodeficient control. The transplantation periods were 1, 2, 3, 4, 8, 12, and 24 weeks. As the result, we did not observe exposure of the transplant or apparent macroscopic inflammatory in all samples. Histological analysis suggested that the femoral head showed focal ossification and thinning in syngeneic transplantation. In allogeneic transplantation, slight invasion of CD3 (+) T cell and the denaturation of the cartilage were observed, suggesting immune reaction against allogeneic cartilage. In xenogeneic transplantation, slight invasion of CD3 (+) cell and CD4 (+) cell and the structure of the perichondrium-like tissue got unclear, suggesting slight immune reaction against xenogeneic cartilage. Our findings suggest that we should carefully investigate for appropriate procedure to control immune reaction against allogeneic cartilage with live chondrocyte and to maintain its cartilage feature for long time.
Impact statement
Clinically, subcutaneous transplantation of allogeneic cartilage is conducted with live cells removed from the tissue. Because live chondrocyte is essential for the maintenance of the cartilage feature, it would be beneficial if cartilage with live chondrocyte could be transplanted subcutaneously without issue even in allogeneic transplantation. We subcutaneously transplanted cartilage with live cells to immunologically normal mouse in syngeneic, allogeneic, and xenogeneic combination. Macroscopically, severe inflammation or exposure of the transplant was not observed. Histologically, signs of immune reaction were observed in allogeneic and xenogeneic transplantations. Taking these, we should carefully investigate for appropriate countermeasures to control immune reaction.
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