Kaipe H, Erkers T, Sadeghi B, Ringdén O
Division of Therapeutic Immunology and Centre for Allogeneic Stem Cell Transplantation, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Bone Marrow Transplant. 2014 Jun;49(6):737-43. doi: 10.1038/bmt.2013.237. Epub 2014 Jan 27.
Mesenchymal stromal cells (MSCs) have immunomodulatory effects and are increasingly being used for the treatment of acute and chronic GVHD. Although they seem immuno-privileged, they induce alloresponses, but the risk of immunization is poorly characterized. After infusion, they first reach the lungs, liver and spleen, and are then difficult to trace. Several mechanisms are involved in stromal cells suppressing alloreactivity, such as induction of regulatory T cells, but whether or not this will also affect leukemic relapse or increase infections is not known. Although several encouraging pilot studies have been published, there have been few prospective randomized trials. There may be a bias in the literature, as negative results are seldom published, and there have been few comparative studies with other immunosuppressive regimens. Most animal models have failed to show any effect on GVHD. Several questions remain to be answered for optimization of stromal cell therapy. Which source is optimal-BM, fat, cord or decidua? Can stromal cells be replaced by exosomes, which culture conditions are most appropriate and at what passage and how frequently should cells be administered? More research is required to move stromal cell therapy forward to become an established treatment for acute and chronic GVHD.
间充质基质细胞（MSCs）具有免疫调节作用，越来越多地被用于治疗急性和慢性移植物抗宿主病（GVHD）。尽管它们似乎具有免疫特权，但它们会引发同种异体反应，不过免疫风险的特征尚不明确。输注后，它们首先到达肺、肝和脾，然后难以追踪。基质细胞抑制同种异体反应涉及多种机制，如诱导调节性T细胞，但这是否也会影响白血病复发或增加感染尚不清楚。尽管已经发表了几项令人鼓舞的初步研究，但前瞻性随机试验很少。文献中可能存在偏差，因为阴性结果很少发表，而且与其他免疫抑制方案的比较研究也很少。大多数动物模型未能显示对GVHD有任何影响。为了优化基质细胞治疗，仍有几个问题有待解答。哪种来源最佳——骨髓、脂肪、脐带还是蜕膜？基质细胞能否被外泌体替代，哪种培养条件最合适，在什么传代时以及细胞应该多久给药一次？需要更多的研究来推动基质细胞治疗成为急性和慢性GVHD的既定治疗方法。
