Prolongation of Cardiac Allograft Survival by Endometrial Regenerative Cells: Focusing on B‐Cell Responses

Abstract : Endometrial regenerative cells (ERCs) have been recently evaluated as an attractive candidate source for emerging stem cell therapies in immunosuppression, but their role in immunoregulation is not fully understood. The present study was designed to investigate their effects, especially on B-cell responses in heart transplantation. In this study, ERCs were noninvasively obtained from menstrual blood. Heart transplantation was performed between C57BL/6 (H-2(b)) donor mice and BALB/c (H-2(d)) recipients. B-cell activation and antibody levels were determined using fluorescence-activated cell sorting, enzyme-linked immunosorbent assay and ELISpot. In this study, we demonstrated that ERCs negatively regulated B-cell maturation and activation in vitro without affecting their viability. ERC treatment prolonged cardiac allograft survival in mice, which was correlated with a decrease in IgM and IgG deposition and circulating antidonor antibodies, as well as with reduction in frequencies of antidonor antibody-secreting CD19(+) B cells. In addition, upon ex vivo stimulation, B cells from ERC-treated heart transplant recipients had impaired proliferation capacity and produced less IgM and IgG antibody. Moreover, ERC treatment of mice receiving ovalbumin (OVA)-aluminum hydroxide vaccine resulted in significant lower numbers of anti-OVA IgG antibody-secreting splenic B cells and lower anti-OVA antibody titres. Our results indicate that therapeutic effects of ERCs may be attributed at least in part by their B-cell suppression and humoral response inhibition, suggesting the potential use of ERCs for attenuating antibody-mediated allograft rejection. The alloantibody-associated episodes of acute and chronic allograft rejection are still prevalent in clinic. This study demonstrates that endometrial regenerative cells (ERCs), a novel source of adult mesenchymal stem cells noninvasively obtained from menstrual blood, inhibit B-cell activation and differentiation with reduced antibody production in a mouse cardiac transplant model. The unique features of the ease of collection, relatively unlimited source, immunomodulatory effect, and hypoimmunogenicity could make ERCs an attractive candidate source for stem cell therapies for the prevention and/or treatment of acute and chronic humoral rejection following transplantation.