Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium
Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium
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DOI：
10.1038/bmt.2008.316
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发表时间：
2009-02-01
影响因子：
4.8
通讯作者：
Bornhaeuser, M.
中科院分区：
文献类型：
--
作者：
von Bonin, M.;Stoelzel, F.;Bornhaeuser, M.
间充质干细胞已被证明介导免疫调节作用。它们已用于类固醇难治性急性GVHD（aGVHD）患者，但其作为靶向aGVHD治疗剂的相关性仍有待确定。在这个病例系列中，我们报告了13例类固醇难治性aGVHD患者，他们接受了来自无关HLA不同供体的骨髓来源MSC在含血小板裂解物的培养基中扩增。MSC的特征在于其形态，表型和功能特性。所有测试的制剂抑制体外活化的CD 4 + T细胞的增殖。MSC以0.9 × 10（6）/kg（范围0.6-1.1）的中位剂量输注。MSC申请的中位数为2（范围1-5）。只有两名患者（15%）反应，不需要任何进一步的免疫抑制治疗的升级。11例患者接受了额外的补救免疫抑制治疗，伴随着进一步的MSC输注，28天后，其中5例（45%）显示出反应。4名患者（31%）在中位随访257天后存活，其中1名患者最初对MSC治疗有反应。在我们的患者队列中，对MSC输注的反应低于先前报道的系列。然而，我们的经验支持MSC治疗类固醇难治性aGVHD的潜在疗效。
Mesenchymal stem cells have been shown to mediate immunomodulatory effects. They have been used in patients with steroid-refractory acute GVHD (aGVHD), but their relevance as a therapeutic agent targeting aGVHD has still to be defined. In this case series, we report 13 patients with steroid-refractory aGVHD who received BM-derived MSC expanded in platelet lysate-containing medium from unrelated HLA disparate donors. MSC were characterized by their morphological, phenotypical and functional properties. All tested preparations suppressed the proliferation of in vitro activated CD4+ T cells. MSC were transfused at a median dosage of 0.9 x 10(6)/kg (range 0.6-1.1). The median number of MSC applications was 2 (range 1-5). Only two patients (15%) responded and did not require any further escalation of immunosuppressive therapy. Eleven patients received additional salvage immunosuppressive therapy concomitant to further MSC transfusions, and after 28 days,five of them (45%) showed a response. Four patients (31%) are alive after a median follow-up of 257 days, including one patient who initially responded to MSC treatment. In our patient cohort, response to MSC transfusion was lower than in the series reported earlier. However, our experience supports the potential efficacy of MSC in the treatment of steroid-refractory aGVHD.