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中华细胞与干细胞杂志(电子版)

中华细胞与干细胞杂志(电子版) ›› 2019, Vol. 09 ›› Issue (01) : 29 -34. doi: 10.3877/cma.j.issn.2095-1221.2019.01.006

所属专题： 文献；

论著

白细胞介素4降低脐带间充质干细胞对造血干细胞分化潜能的维持能力
郭冬阳1, 卢艳2, 岳影星1, 杨舟鑫1,†()   
  1. 1. 310030　杭州，浙江医院重症医学实验室
    2. 310030　杭州，浙江医院放射科
  • 收稿日期:2018-11-13 出版日期:2019-02-01
  • 通信作者: 杨舟鑫
  • 基金资助:
    国家自然科学基金(81801902，81801903); 浙江省医药卫生科技计划(2017KY001)

Interleukin-4 reduces the supportive ability of umbilical cord mesenchymal stem cells on differentiation potentialof hematopoietic stem cells

Dongyang Guo1, Yan Lu2, Yingxing Yue1, Zhouxin Yang1,†()   

  1. 1. Laboratory of Critical Care Medicine, 2Department of Radiology, Zhejiang Hospital, Hangzhou 310013, China
  • Received:2018-11-13 Published:2019-02-01
  • Corresponding author: Zhouxin Yang
  • About author:
    Corresponding author: Yang Zhouxin, Email:
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引用本文：

郭冬阳, 卢艳, 岳影星, 杨舟鑫. 白细胞介素4降低脐带间充质干细胞对造血干细胞分化潜能的维持能力[J]. 中华细胞与干细胞杂志(电子版), 2019, 09(01): 29-34.

Dongyang Guo, Yan Lu, Yingxing Yue, Zhouxin Yang. Interleukin-4 reduces the supportive ability of umbilical cord mesenchymal stem cells on differentiation potentialof hematopoietic stem cells[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2019, 09(01): 29-34.

目的

探讨白细胞介素4（IL-4）对脐带间充质干细胞（UC-MSC）维持造血干细胞分化的影响。

方法

将UC-MSC与脐带血CD34+造血干细胞按照造血支持能力常用的方案共培养，实验分为对照组和IL-4组，IL-4处理组加入IL-4（20 ng/ml）培养14 d。收集细胞并计数，使用流式细胞仪检测表达CD34的细胞比例。取3×103个细胞，加入到半固体培养基，培养14 d后，通过倒置显微镜观察比较各种集落的形成，并使用流式细胞仪分析其中巨噬细胞和粒细胞表面特异性蛋白CD11b、CD14和CD15的表达。对两独立样本进行t检验统计学分析。

结果

加入IL-4后，共培养体系中细胞数量（1.31±0.05）×105个/孔与对照组（2.80±0.28）×105?个/孔相比下降，差异有统计学意义（t = 7.31，P < 0.05），并且流式细胞分析显示其中的CD34+细胞比例也有降低。3×103个IL-4组得到的细胞形成巨噬细胞集落形成单位的能力（9.33±1.53）?个/孔较对照组（17.67±0.58）个/孔有明显下降，差异有统计学意义（t = 8.84，P?< 0.001）；形成粒-巨噬集落形成单位的能力（15.67±3.22）个/孔较对照组（29.33±4.04）?个/?孔有明显下降，差异有统计学意义（t = 4.58，P < 0.05）；形成总集落单位的能力（39.33±9.07）个/?孔较对照组（62.67±6.66）?个/?孔也有下降，差异有统计学意义（t = 3.59，P < 0.05）。IL-4组得到的细胞分化出的细胞总数（3.67±1.71）×105个/孔与对照组（9.50± 3.13）×105个/孔相比也明显下降，差异有统计学意义（t = 2.83，P < 0.05），而流式细胞术分析发现分化成的细胞中CD14+细胞比例也下降。

结论

IL-4可以降低UC-MSC对造血干细胞分化潜能的维持能力，提示在Ⅱ型辅助T细胞相关体液免疫疾病中使用间充质干细胞治疗时，也需要兼顾机体造血相关功能。

关键词: 脐带间充质干细胞, 造血干细胞, 分化潜能, 白细胞介素4
Objective

Umbilical cord mesenchymal stem cells (UC-MSC) are a hot research field because of its unique advantages. UC-MSC possess the ability of maintaince the differentiation potential of hematopoietic stem cells, and we studied the effect of interleukin-4 on this ability.

Methods

Umbilical cord mesenchymal stem cells were co-cultured with cord blood CD34+ cells with or without IL-4. CD34+ cells were counted after 14 days. Moreover, colony forming ability of cells was evaluated. CD11b, CD14 and CD15 expression of cells from colony forming assay was assayed by flow cytometry. Statistical analysis was performed by unpaired t-test. After IL-4 was added, the number of cells (1.31±0.05) ×105 cells/well decreased significantly compared with the control group (2.80±0.28) ×105 cells/well (t = 7.31, P < 0.05) , and flow cytometry analysis showed that the proportion of CD34+ cells in the co-culture system also decreased. The ability of IL-?4-treated cells to form colony forming unit-macrophage (9.33±1.53 per well) was significantly lower than that of the control group (17.67±0.58 per well, t = 8.84, P < 0.001) ; The ability to form colony forming unit-granulocyte/macrophage (15.67±3.22 per well) was significantly lower than that of the control group (29.33±4.04 per well, t = 4.58, P < 0.05) . The ability to form total colony forming units (39.33±9.07 per well) was also lower than that of the control group (62.67±6.66 per well, t = 3.59, P < 0.05) . The total number of cells differentiated from IL-4 group (3.67±1.71) ×105 cells/well was also significantly lower than that of the control group (9.50±3.13) ×105 cells/?well, (t = 2.83, P < 0.05) , and flow cytometry analysis showed that the ratio of CD14+ cells in differentiated cells was also lower.

Conclusion

IL-4 can reduce the maintenance ability of umbilical cord mesenchymal stem cells on hematopoietic stem cells differentiation, suggesting that when mesenchymal stem cells are used in treatment of type II helper T cell-related humoral immune diseases, the hematopoietic related functions should also be considered.

Key words: Umbilical cordmesenchymal stem cells, Hematopoietic stem cells, Differentiation potential, Interleukin-4
图1 IL-4处理后UC-MSC与造血干细胞共培养体系细胞状态
图2 IL-4处理后UC-MSC与造血干细胞共培养体系细胞数量的影响
图3 IL-4处理对共培养体系中CD34+细胞比例的影响
表1 IL-4处理后共培养体系中细胞集落形成能力的变化（ ± s）
分组 样本数 BFU-E CFU-G CFU-M CFU-GM CFU- GEMM 总集落形成单位 总细胞数（×105）
对照组 3 1.00±1.00 13.33±3.22 17.67±0.58 29.33±4.04 1.33±1.53 62.67±6.66 9.50±3.13
IL-4组 3 1.00±1.73 12.33±2.52 9.33±1.53 15.67±3.22 1.00±1.00 39.33±9.07 3.67±1.71
t值 ? 0.00 0.42 8.84 4.58 0.32 3.59 2.83
P值 ? 0.99 0.69 < 0.01 < 0.05 0.77 < 0.05 < 0.05
图4 IL-4处理对共培养体系中细胞分化成CD11b+、CD14+和CD15+细胞能力的影响
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