Tissue repair and donor-dependent immune responses after allogeneic skeletal muscle-derived cell sheet transplantation in a rat gastric ulcer model.

Cell transplantation using cell sheet technology is a promising regenerative approach that enables the delivery of a large number of viable cells while preserving cell-cell interactions and extracellular matrix. However, the clinical application of autologous cell sheets is limited by donor-site invasiveness, prolonged preparation time, and high manufacturing costs. Allogeneic cell sheets may overcome these limitations, but their therapeutic effects and immunological profiles require further clarification. In this study, we investigated the tissue-repair effects and immune responses associated with allogeneic skeletal muscle-derived cell (SMDC) sheet transplantation. In vitro analyses showed that human SMDCs suppressed activated T-cell proliferation in a cell number-dependent manner, lacked co-stimulatory molecules, and expressed immune checkpoint ligands, suggesting a potentially low-immunogenic and immunomodulatory phenotype. For in vivo evaluation, L8-derived syngeneic comparator sheets and allogeneic SMDC sheets derived from different rat strains were transplanted onto the serosal surface in a rat gastric ulcer model. SMDC sheet transplantation promoted early ulcer repair without increasing systemic inflammatory responses, as assessed by serum C-reactive protein levels. Histological analyses revealed limited macrophage and T-cell infiltration at the transplantation sites, although the extent of local immune responses varied depending on donor-recipient strain combinations. Transcriptomic analysis of ulcer tissues showed that the L8-derived syngeneic comparator and selected allogeneic groups shared downregulation of inflammation-related pathways, whereas another allogeneic donor strain induced a distinct transcriptional profile. These findings suggest that allogeneic SMDC sheets can promote early tissue repair without inducing overt systemic inflammatory activation. However, donor-recipient strain compatibility may influence local immunological and transcriptional responses after transplantation. The observed effects are consistent with early paracrine and immunomodulatory mechanisms, although direct cell tracking and more detailed immunological analyses are required. Allogeneic SMDC sheets may represent a potential ready-to-use strategy for gastrointestinal tissue repair, provided that appropriate donor selection and further preclinical validation are performed.