Acellular allogeneic nerve grafting combined with bone marrow mesenchymal stem cell transplantation for the repair of long-segment sciatic nerve defects:biomechanics and validation of mathematical models

We hypothesized that a chemically extracted acellular allogeneic nerve graft used in combination with bone marrow mesenchymal stem cell transplantation would be an effective treatment for long-segment sciatic nerve defects.To test this,we established rabbit models of 30 mm sciatic nerve defects,and treated them using either an autograft or a chemically decellularized allogeneic nerve graft with or without simultaneous transplantation of bone marrow mesenchymal stem cells.We compared the tensile properties,electrophysiological function and morphology of the damaged nerve in each group.Sciatic nerves repaired by the allogeneic nerve graft combined with stem cell transplantation showed better recovery than those repaired by the acellular allogeneic nerve graft alone,and produced similar results to those observed with the autograft.These findings confirm that a chemically extracted acellular allogeneic nerve graft combined with transplantation of bone marrow mesenchymal stem cells is an effective method of repairing long-segment sciatic nerve defects.

Delayed allogeneic skin graft rejection in CD26-deficient mice

Organ transplantation is an effective therapeutic tool for treating many terminal diseases.However,one of the biggest challenges of transplantation is determining how to achieve the long-term survival of the allogeneic or xenogeneic transplant by,for example,preventing transplant rejection.In the current study,CD26 gene-knockout mice were used to investigate the potential role of CD26/dipeptidyl peptidase-4(DPPIV)in allogeneic skin graft rejection by tail-skin transplantation.Compared with wild-type(CD26^(+/+))counterparts,CD26^(-/-)mice showed reduced necrosis of grafts and delayed graft rejection after skin transplantation.Concentrations of serum IgG,including its subclasses IgG1 and IgG2a,were significantly reduced in CD26^(-/-)mice during graft rejection.Moreover,after allogeneic skin transplantation,the secretion levels of the cytokines IFN-γ,IL-2,IL-6,IL-4,and IL-13 were significantly reduced,whereas the level of the cytokine IL-10 was increased in the serum of CD26^(-/-)mice compared with that in the serum of CD26^(+/+)mice.Additionally,the concentration of IL-17 in serum and the percentage of cells secreting IL-17 in mouse peripheral blood lymphocytes(MPBLs)were both significantly lower,while the percentage of regulatory T cells(Tregs)was significantly higher in MPBLs of CD26^(-/-)mice than in those of CD26^(+/+)mice.Furthermore,a lower percentage of CD8^(+)T cells in MPBLs and fewer infiltrated macrophages and T cells in graft tissues of CD26^(-/-)mice were detected during graft rejection.These results indicate that CD26 is involved in allogeneic skin graft rejection and provides another hint that CD26 deficiency leads to less rejection due to lower activation and proliferation of host immune cells.