Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska University Hospital, Stockholm, Sweden.
Stem Cells. 2013 Mar;31(3):592-601. doi: 10.1002/stem.1314.
The placenta protects the fetus from the mother's immune system. We have previously found that fetal membrane cells (FMCs) isolated from term placenta prevent alloreactivity in vitro. FMCs share many features with bone marrow-derived mesenchymal stromal cells (MSCs), which we previously introduced to treat severe acute graft-versus-host disease (GVHD). Here, we tested FMCs for treatment of steroid-refractory acute GVHD. After two passages in culture, approximately 10(9) FMCs were obtained from one single placenta, although not all cells from passage 0 and passage 1 were used for expansion. The FMCs were positive for CD29, CD44, CD73, CD90, CD105, and CD49d but were negative for hematopoietic, endothelial, and epithelial markers. Microsatellite polymorphism analysis showed that FMCs were of maternal origin. All FMCs used showed normal karyotype. Nine patients who had undergone hematopoietic stem cell transplantation (HSCT) and who had developed steroid-refractory grade III-IV acute GVHD were given 0.9-2.8 × 10(6) FMCs per kg at 15 infusions. Median age was 57 years. There was no toxicity from infusion of FMCs in eight patients. One patient had seizures after infusion. Two of eight evaluable patients had a complete response and four had a partial response, giving an overall response rate of 75%. Two patients showed no response at all. Three patients are alive from 6 to 21 months after HSCT. One patient is well and two have chronic GVHD. Thus, FMCs may be successfully used for immune modulation and tissue repair.
胎盘可保护胎儿免受母亲免疫系统的攻击。我们之前发现，从足月胎盘中分离出来的胎膜细胞（FMCs）可在体外防止同种异体反应。FMCs 与骨髓来源的间充质基质细胞（MSCs）具有许多共同特征，我们之前曾用 MSCs 来治疗严重的急性移植物抗宿主病（GVHD）。在这里，我们测试了 FMCs 治疗类固醇难治性急性 GVHD 的效果。经过两次传代培养，大约可从一个胎盘获得 10(9)个 FMCs，尽管并非所有传代 0 和传代 1 的细胞都用于扩增。FMCs 表达 CD29、CD44、CD73、CD90、CD105 和 CD49d，而不表达造血细胞、内皮细胞和上皮细胞标志物。微卫星多态性分析表明 FMCs 来自母体。所有使用的 FMCs 均显示正常核型。9 名接受过造血干细胞移植（HSCT）并出现类固醇难治性 III-IV 级急性 GVHD 的患者，在 15 次输注中每公斤给予 0.9-2.8×10(6)个 FMCs。中位年龄为 57 岁。在 8 名患者中，输注 FMCs 无毒性。1 名患者输注后出现癫痫发作。8 名可评估患者中的 2 名完全缓解，4 名部分缓解，总缓解率为 75%。2 名患者完全没有反应。3 名患者在 HSCT 后 6 至 21 个月时仍存活。1 名患者情况良好，2 名患者患有慢性 GVHD。因此，FMCs 可能成功地用于免疫调节和组织修复。
