Sundin M, Orvell C, Rasmusson I, Sundberg B, Ringdén O, Le Blanc K
Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden.
Bone Marrow Transplant. 2006 Jun;37(11):1051-9. doi: 10.1038/sj.bmt.1705368.
Allogeneic stem cell transplantation is often complicated by reactivation of herpesviruses. Mesenchymal stem cells (MSC) are immunomodulatory and may be used to treat graft-versus-host disease. We investigated if herpesviruses infect and can be transmitted by MSC, and if MSC suppress immune responses to various infectious agents. Mesenchymal stem cells from healthy seropositive donors were evaluated with polymerase chain reaction for the most common herpesviruses: cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2, Epstein-Barr virus (EBV) and varicella zoster virus. The cytopathological effect (CPE) was investigated and viral antigens analyzed by immunofluorescence after in vitro exposure to CMV, HSV-1 and EBV. We also studied MSC effect on lymphocyte stimulation induced by various infectious agents. No viral DNA could be detected in MSC isolated from healthy seropositive individuals. However, a CPE was noted and intracellular viral antigens detected after infection in vitro by CMV and HSV-1, but not by EBV. The CMV and HSV-1 infections were productive. Lymphocyte proliferation by herpesviruses, candida mannan and protein A from Staphylococcus aureus was suppressed by MSC. The data indicate that the risk of herpesvirus transmission by transplantation of MSC from healthy seropositive donors is low. However, MSC may be susceptible to infection if infused in a patient with CMV or HSV-1 viremia. MSC transplantation may compromise the host's defense against infectious agents.
异基因干细胞移植常因疱疹病毒再激活而复杂化。间充质干细胞（MSC）具有免疫调节作用，可用于治疗移植物抗宿主病。我们研究了疱疹病毒是否感染MSC并可通过其传播，以及MSC是否抑制对各种感染因子的免疫反应。对来自健康血清学阳性供体的间充质干细胞进行聚合酶链反应评估，检测最常见的疱疹病毒：巨细胞病毒（CMV）、单纯疱疹病毒1型（HSV-1）、单纯疱疹病毒2型、爱泼斯坦-巴尔病毒（EBV）和水痘带状疱疹病毒。在体外暴露于CMV、HSV-1和EBV后，研究细胞病变效应（CPE）并通过免疫荧光分析病毒抗原。我们还研究了MSC对各种感染因子诱导的淋巴细胞刺激的影响。从健康血清学阳性个体分离的MSC中未检测到病毒DNA。然而，在体外感染CMV和HSV-1后观察到CPE并检测到细胞内病毒抗原，但EBV感染后未出现此情况。CMV和HSV-1感染具有增殖性。MSC抑制了疱疹病毒、白色念珠菌甘露聚糖和金黄色葡萄球菌蛋白A诱导的淋巴细胞增殖。数据表明，来自健康血清学阳性供体的MSC移植传播疱疹病毒的风险较低。然而，如果将MSC输注给患有CMV或HSV-1病毒血症的患者，MSC可能易受感染。MSC移植可能会损害宿主对感染因子的防御能力。
