脐带间充质干细胞治疗再生障碍性贫血18例临床研究

目的 初步观察脐带间充质干细胞（umbilical cord mesenchymal stem cells,UC-MSC）治疗再生障碍性贫血（aplastic anemia,AA）患者的疗效和安全性.方法 18例AA患者,中位年龄28（7～49）岁,重型AA 10例,非重型AA 8例;7例曾接受免疫抑制治疗,均无效.从正常足月分娩胎儿的脐带分离培养UC-MSC,静脉输注给患者,每次输注细胞数为1×106/kg,每周输注1～2次.观察治疗前、后患者外周血细胞计数、骨髓细胞学、骨髓活检、外周血CD3＋CD4＋、CD3＋CD8＋T淋巴细胞亚群比例及临床症状等,观察治疗相关不良反应.结果 18例患者接受UC-MSC输注中位次数38 （12～96）次,中位治疗时间8（3～16）月,中位随访时间31 （6～36）月.其中3例患者基本治愈,7例缓解,1例明显进步,2例患者贫血和出血症状好转、输血间隔延长,5例无效;总有效率72.2％.7例既往对免疫抑制剂无效的患者中,4例有效.12例患者在治疗前外周血CD4＋/CD8＋细胞比值倒置,治疗后11例不同程度升高（其中7例恢复正常）.所有患者均未出现明显的治疗相关不良反应.结论 UC-MSC治疗有助于改善AA患者的骨髓造血功能,短期观察未发现不良反应,尤其对免疫抑制治疗无效、不适合移植或不能耐受相关副作用的AA患者具有重要的临床价值.

Umbilical cord mesenchymal stem cells in treatment of 18 patients with aplastic anemia

Objective To explore the efficacy and safety of umbilical cord mesenchymal stem cells （UC-MSC） in the treatment of aplastic anemia （AA）. Methods Eighteen patients with AA whose median age was 28 （7~49） were enrolled, including 10 severe AA; 7 of whom received immunosuppression treatment, but didn＇ t got good effect. UC-MSC were isolated from the umbilical cords of healthy fetuses and then cultured. The third to fifth generation ceils were intravenously administered to the patients 1 × 10^6/kg once or twice a week. Before and after the infusion, complete blood cell counting, bone marrow aspiration, bone marrow biopsy, flow cytometry analysis of lymphocyte subsets, and clinical symptoms were observed. And treatment- related adverse reactions were observed. Results After a median of 38-time （12-96 times） infusions of UC-MSC 8-month（3-16 months） treatment, and 31-month （6~36 months） follow-up, 3 cases were almost completely cured, 7 cases relieved, 1 case improved, 2 cases got better in anemia and bleeding and longer transfusion interval, 5 didn＇ t responded to the treatment, with a total response rate of 72.2%. 4 of 7 front- line immunosuppressive-resistant patients responded to the treatment. 7 of 12 patients with inverted CD4＋/ CD8＋ recovered back to normal. No patient occurred adverse reaction. Conslusions UC-MSC in the treatmentof AA is effective and safe and has no short term adverse reactions. It is a good therapy for the patients not responding to immunosuppression treatment, not suitable for transplant, or not able to tolerate the adverse reactions.