Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
Stem Cells Transl Med. 2017 Mar;6(3):778-787. doi: 10.5966/sctm.2016-0206. Epub 2016 Oct 26.
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 ) donor mice and BALB/c (H-2 ) 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. Stem Cells Translational Medicine 2017;6:778-787.
子宫内膜再生细胞（ERCs）最近被评估为一种有吸引力的候选来源，可用于新兴的免疫抑制干细胞治疗，但它们在免疫调节中的作用尚不完全清楚。本研究旨在探讨它们的作用，特别是在心脏移植中的 B 细胞反应。在这项研究中，ERC 从月经血中无创获得。C57BL/6（H-2）供体小鼠和 BALB/c（H-2）受体之间进行心脏移植。使用荧光激活细胞分选、酶联免疫吸附试验和 ELISpot 测定 B 细胞激活和抗体水平。在这项研究中，我们证明 ERC 在体外可负调控 B 细胞成熟和激活，而不影响其活力。ERC 治疗延长了小鼠心脏移植物的存活时间，这与 IgM 和 IgG 沉积和循环抗供体抗体减少以及抗供体抗体分泌 CD19 B 细胞频率降低有关。此外，在体外刺激下，来自 ERC 治疗的心脏移植受者的 B 细胞增殖能力受损，产生的 IgM 和 IgG 抗体减少。此外，ERC 处理接受卵清蛋白（OVA）-氢氧化铝疫苗的小鼠导致抗 OVA IgG 抗体分泌脾 B 细胞数量显著减少，抗 OVA 抗体滴度降低。我们的结果表明，ERC 的治疗效果至少部分归因于它们对 B 细胞的抑制和体液反应的抑制，这表明 ERC 有潜力用于减轻抗体介导的同种异体移植排斥反应。《干细胞转化医学》2017 年；6:778-787.
