Abstract
Background Immunosuppression risks are a major concern with vascularized composite allotransplantation
(VCA). As an emerging strategy, the antirejection role played by mesenchymal stem
cells (MSCs) is receiving attention. However, the current literature reports are inconclusive
regarding the robustness of the MSC monotherapy. Using a rat forelimb VCA model, this
study tested the robustness of the immunomodulation efficacy of gingival-derived MSCs
(GMSCs) and bone marrow–derived MSCs (BMMSCs).
Methods Forelimbs were transplanted on pairs of major histocompatibility complex–incompatible
rats (Wistar-Kyoto donor, Lewis [LEW] recipient). Twenty-four LEW rats were randomly
divided into four groups, including control (no treatment) and three treatment groups:
rapamycin (2 mg/kg/day for 28 days, postoperatively), BMMSC and GMSC, both of which
received donor-derived stem cells administered intravenously on postoperative days
(PODs) 0, 3, 7, and 14. Rejection was considered as 80% skin necrosis of the allograft.
Microcomputed tomography (µCT) was performed to evaluate healing at osteosynthesis
site. On POD 14, limbs from each group underwent histological analysis and rejection
grading using the Banff system.
Results Both BMMSC (15.0 days) and GMSC (14.7 days) treatment failed to prolong VCA survival
in comparison with the control group (13.8 days; p > 0.050), while the rapamycin significantly delayed acute VCA rejection (24.5 days;
p = 0.003). Micro-CT imaging revealed no gross visual difference across all groups.
Histology revealed that the control group was most severely affected (grades III and
IV) followed by MSC (grade II) and rapamycin (grade I).
Conclusion MSC monotherapy, both BMMSC and GMSC, did not inhibit rejection in our VCA model.
Skin immunogenicity is an important issue in promoting rejection, and a concomitant
immunosuppression regimen should be considered to prolong allograft survival.
Keywords
vascularized composite allotransplantation - gingival-derived mesenchymal stem cells
- bone marrow–derived mesenchymal stem cells
