一项多中心临床研究：脐带间充质干细胞移植治疗系统性红斑狼疮

坤明

来源：生物谷 2014-6-16 9:22:34 m" d# i, X8 y0 g

8 F! G  T: M, ?0 y7 a近日，国际学术期刊Arthritis Research & Therapy在线发表了南京大学附属医院鼓楼医院、江苏大学附属医院以及苏北人民医院、江苏省人民医院等多家研究中心署名的题为Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus： a multicenter clinical study的研究论文，报道了一项用脐带间充干细胞移植治疗严重系统性红斑狼疮的多中心临床试验。6 E9 L0 X0 z* R4 v( J
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系统性红斑狼疮（SLE）是一种常见的和潜在致命的自身免疫性疾病。其特征在于机体产生大量抗体，并与体内相应的自身抗原结合形成相应的免疫复合物，对肾、心血管、神经、肌肉骨骼和皮肤产生系统损害。
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+ {) `- k+ s/ T% Y5 |该研究中的四个临床中心入选了40例严重的SLE患者。在第1天和第7天，采用同种异体的脐带间充质干细胞静脉注射进行治疗。主要考察的是安全性方面，其他考察还包括主要临床响应、部分临床响应以及复发率。临床反应指数包括SLEDAI分值、BILAG分值、以及肾功能指标。患者总的生存率为92.5％（37/40），脐带间充质干细胞移植后患者的耐受性良好，且无观察到与移植相关的不良事件。13例和11例病人分别在之后12个月的随访中完成了MCR(13/40， 32.5%)和PCR （13/40，32.5％）的统计。) ]( J. w" z  p, d/ U$ p
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在最初的临床反应之后，有3例和4例病人分别在随访的第9个月和12个月时疾病复发。在随访的3、6、9和12个月时，患者SLEDAI评分显着减少。在随访的3个月时，患者总BILAG分值显着降低并在此之后的随访过程中持续减少，肾脏、造血和皮肤系统的BILAG分值显着改善。对于那些有系统性红斑狼疮肾炎的患者，24小时蛋白尿在移植之后下降，与随访9月与12月时具有统计学差异。在第6个月时，血清肌酐和尿素氮下降到最低水平，由于有7例复发的病人，这些数值在9月和12月时略微上升。此外，移植之后血清白蛋白和补体3有所增加，在随访的第6个月达到顶峰，然后在第9和12月随访时，略有下降。血清抗核抗体、抗双链DNA抗体在MSCT之后下降，与随访的第3个月时有统计学差异。, k0 |. n+ |$ L0 C3 q( R  ~) _

$ K$ Y  }; Q# d总之，本试验显示脐带间充质干细胞移植能够对SLE患者产生满意的临床疗效，然而，一些病例在6个月后产生疾病的复发，说明有必要在移植治疗6个月后再次进行移植治疗。) P6 X2 I. ?% ~5 Y7 ]9 R

4 o% I" z/ S! p1 v该研究得到了国家自然科学基金委及江苏省卫生厅的资助。

坤明

Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus： a multicenter clinical study
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$ W" U$ i/ f* R7 U0 F- w- u% ^Systemic lupus erythematosus (SLE) is a common and potentially fatal autoimmune disease characterized by autoantibodies associated with multiorgan injury， including the renal， cardiovascular， neural， musculoskeletal， and cutaneous systems ./ S3 Q0 S2 G8 E$ _
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Forty patients with active SLE were enrolled from 4 clinical centers in China. Allogenic UCMSCs were infused intravenously on days 0 and 7. Primary endpoints were safety profiles.Second endpoints included major clinical response (MCR)， partial clinical response (PCR)and relapse. Clinical index including SLEDAI score， BILAG score， renal functional indices were also determined.6 Y2 f; ~" s  R: x/ A2 P& q

5 }; c5 p$ g9 ?0 _- [/ ]The overall survival rate was 92.5% (37/40). UC-MSCT was well tolerated， and no transplantation-related adverse event was observed. Thirteen and eleven patients achieved MCR (13/40， 32.5%) and PCR (11/40， 27.5%) during 12 months follow-up， respectively. Then three and four patients experienced disease relapse at 9 (12.5%) and 12 (16.7%) months follow-up， after a prior clinical response. SLEDAI score significantly decreased at 3， 6， 9 and 12 months follow-up.
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Total BILAG score markedly decreased at 3 months and continued to decrease at subsequent follow-up visits. BILAG scores for renal， hematopoietic and cutaneous systems significantly improved. For those with lupus nephritis， 24-hour proteinuria declined after transplantation， with statistical differences at 9 and 12 months. Serum creatinine and urea nitrogen decreased to the lowest level at 6 months， while these values slightly increased at 9 and 12 months as a result of 7 relapsed cases. In addition， serum levels of albumin and complement 3 increased after MSCT， peaked at 6 months and then slightly declined at 9 and 12 months follow-up. Serum antinuclear antibody and anti-double-strand DNA antibody decreased after MSCT， with statistical differences at 3 months follow-up.9 \3 I" t  A& s  n* I( e
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UC-MSCT results in satisfactory clinical response in SLE patients. However， several cases experienced disease relapse after 6 months， indicating the necessity to repeat MSCT after 6 months.