Recipient bone marrow‐derived stromal cells prolong graft survival in a rat hind limb allotransplantation model

Abstract

BMSCs induce T cell hyporesponsiveness and prolong graft survival in the rat vascularized composite allotransplantation model. BMSCs exhibit immunomodulatory properties against acute rejection that can be realized without the need for significant recipient immunosuppression.

Induced pluripotent stem cell‐derived mesenchymal stem cells prolong hind limb survival in a rat vascularized composite allotransplantation model

“…When considering clinical settings, donor‐derived MSCs face the potential problem of their future applicability, in terms of the associated invasive procedure and the brain‐dead donor. On the other hand, recipient‐derived MSCs provide the distinct advantage of easy access, nonimmunogenicity, and cell preparation or even pretreatment ahead of transplantation (Cheng et al, ; Ikeguchi et al, ). In animal experiments in this study, we used human iMSCs to investigate their immunomodulatory effects in the rat VCA model for future clinical situations.…”

“…Plasma samples from each recipient rat were taken within 2 days before transplantation, and at 10, 14, and 17 days after transplantation. Approximately, 250 μl of blood was obtained from each recipient's caudal vein at each time point, and separated plasma samples were stored at −80°C for later ELISA analysis, as described elsewhere (Ikeguchi et al, ; Oda et al, ). Plasma concentrations of IL‐2, IL‐10, TNFα, and IFN‐γ were determined using standard rat ELISA kits (R&D Systems, Minneapolis, MN).…”

“…To reduce the doses of conventional immunosuppressive drugs, the administration of mesenchymal stem cells (MSCs) has emerged as a novel cell therapy for immunomoduration (Ikeguchi et al, 2017;Plock et al, 2015). Bone marrow-derived MSCs (BMMSCs) and adipose-derived MSCs (ADMSCs) are both capable of inhibiting activated T cells, B cells, natural killer (NK) cells, and dendritic cells (Rasmusson, Ringden, Sundberg, & Blank, 2003;Tse, Pendleton, Beyer, Egalka, & Guinan, 2003).…”

“…Bone marrow-derived MSCs (BMMSCs) and adipose-derived MSCs (ADMSCs) are both capable of inhibiting activated T cells, B cells, natural killer (NK) cells, and dendritic cells (Rasmusson, Ringden, Sundberg, & Blank, 2003;Tse, Pendleton, Beyer, Egalka, & Guinan, 2003). BMMSCs and ADMSCs, whether harvested from donors or recipients, have demonstrated improvement of allograft survival time (Ikeguchi et al, 2017;Plock et al, 2015;Ramirez et al, 2014). However, their accessibility, limited source, and the associated invasive procedure have been a matter of concern.…”

Relative antigenicity of components in vascularized composite allotransplants: An experimental study of microRNAs expression in rat hind limb transplantation model

“…However, they also reported that whole‐limb allografts demonstrated different antigenicity from grafts transplanted as individual components. VCAs sometimes include bone marrow, which contains bone marrow‐derived stromal cells and induces mixed chimerism to some extent (Ikeguchi et al, ). This might reduce the antigenicity when a VCA is transplanted in a whole limb.…”