人脐带间充质干细胞对猕猴糖尿病治疗效果的研究

doi:10.3877/cma.j.issn.2095-1221.2017.03.002

中华细胞与干细胞杂志(电子版) ›› 2017, Vol. 07 ›› Issue (03) : 131 -135. doi: 10.3877/cma.j.issn.2095-1221.2017.03.002

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人脐带间充质干细胞对猕猴糖尿病治疗效果的研究

阮光萍¹, 刘菊芬¹, 李自安¹, 王金祥¹, 庞荣清¹, 潘兴华¹^,^†(

)

^1. 650032　昆明，成都军区昆明总医院细胞生物治疗中心　干细胞与免疫细胞生物医药技术国家地方联合工程实验室　云南省细胞治疗技术转化医学重点实验室

收稿日期:2016-08-02 出版日期:2017-06-01
通信作者: 潘兴华
基金资助:
国家科技支撑计划(2014BI01B01); 云南省科技计划重点项目(2013CA005); 云南省应用基础研究计划重点项目(2015FA039)

Safety and efficacy of human umbilical cord mesenchymal stem cells for diabetes in macaques

Guangping Ruan¹, Jufen Liu¹, Zi’an Li¹, Jinxiang Wang¹, Rongqing Pang¹, Xinghua Pan¹^,^†()

^1. the Cell Biological Therapy Center of Kunming General Hospital of Chendu Military Commend, the Integrated Engineering laboratory of Cell Biological Medicine of State and Regions, the Transfer Medicine Key Laboratory of Cell Therapy Technology of Yunan Province, the Stem Cell Engineering laboratory of Yunan Province, Kunming 650032, China

Received:2016-08-02 Published:2017-06-01
Corresponding author: Xinghua Pan
About author:
Corresponding author:Pan Xinghua, Email:xinghuapan@aliyun.com

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引用本文：

阮光萍, 刘菊芬, 李自安, 王金祥, 庞荣清, 潘兴华. 人脐带间充质干细胞对猕猴糖尿病治疗效果的研究[J/OL]. 中华细胞与干细胞杂志(电子版), 2017, 07(03): 131-135.

Guangping Ruan, Jufen Liu, Zi’an Li, Jinxiang Wang, Rongqing Pang, Xinghua Pan. Safety and efficacy of human umbilical cord mesenchymal stem cells for diabetes in macaques[J/OL]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2017, 07(03): 131-135.

目的

通过用人脐带间充质干细胞（huMSCs）治疗猕猴糖尿病模型观察其血糖的变化。

方法

猕猴9只，分为对照组3只和模型组6只，模型组通过高糖高脂饮食及静脉注射链尿佐菌素（STZ）诱导成糖尿病模型，两组间比较用t检验。12周时再分为模型对照组3只和治疗组3只，治疗组每只每周静脉回输huMSCs 1×10⁶个/kg，连续3周，每周检测各组血糖变化，三组间比较用方差分析。

结果

两组猕猴高糖高脂饮食喂养第8周时模型组空腹血糖值[（22.00±3.00）mmol/L]与对照组[（4.75±0.20）mmol/L]相比差异有统计学意义（t = 9.94，P < 0.01）。40周时1只猕猴因糖尿病死亡，病理切片证实心、肝、脾、肺、肾和胰腺均有病变，符合糖尿病特征。huMSCs治疗后，3周血糖连续下降，到第4周对照组、模型组、治疗组空腹血糖分别为（4.85±0.35）mmol/L、（18.20±1.00）mmol/L、（4.09±0.50）mmol/L，3组差异有统计学意义（F = 388.10，P < 0.01）。两两比较结果表明对照组和模型组比较差异有统计学意义（t = 24.173，P < 0.01），模型组与治疗组比较差异有统计学意义（t = 25.549，P = 0.014）。

结论

STZ联合高糖高脂饲料能成功诱导出猕猴糖尿病模型，用huMSCs能有效降低血糖，使糖尿病猕猴恢复正常血糖，方法简便。

关键词: 猕猴属, 糖尿病, 病理切片, 血糖, 脐带, 间质干细胞移植

Objective

To evaluate the safety and efficacy of human umbilical cord mesenchymal stem cells (huMSCs) in the macaque model of diabetes.

Methods

Nine macaques were divided into either control group (n = 3) or model group (n = 6) . Diabetes was induced by high-sugar, high-fat diet and intravenous injection of streptozotocin (STZ) . Comparison between the two groups was performed using t test. At 12 weeks diabetic macaques were subdivided into the model control group (n = 3) and the treatment group (n = 3) , and the treatment group was given weekly intravenous transfusion of 1×10⁶ huMSCs per kilogram of body weight for 3 weeks. Blood sugar levels were measured weekly. Comparison among the three groups was performed using variance analysis.

Results

At the 8th week, the fasting blood glucose level increased significantly in the model group (22.00±3.00) mmol/L. Compared with the control group (4.89±0.16) mmol/L, the difference was statistically significant (t = 9.94, P < 0.01) . A monkey died due to diabetes at 40 weeks. Pathological examination showed heart, liver, spleen, lungs, kidneys and pancreas had the characteristics of diabetes. After huMSCs therapy, blood sugar continuously declined for 3 weeks. At the fourth week, the fasting blood glucose of the control group, the model group and the treatment group were 4.85±0.35 mmol/L, 18.20±1.00 mmol/L, and 4.09±0.50 mmol/L respectively. There was significant difference between the control group and the model group (t = 24.173, P < 0.01) , and between the model group and the treatment group (t = 25.549, P = 0.014) .

Conclusion

STZ and high-sugar, high-fat diet can induce diabetes in macaques. HuMSCs is simple and effective in treating diabetes.

Key words: Macaca, Diabetes mellitus, Pathological section, Blood glucose, Umbilical cord, Mesenchymal stem cell transplantation

图1 经高糖高脂喂养后两组猕猴空腹血糖结果

表1 经高糖高脂喂养后2组猕猴0 ~ 6周空腹血糖的结果（mmol/L， ± s）

分组	只数	0周	1周	2周	3周	4周	5周	6周
对照组	3	4.80±0.20	4.90±0.30	5.00±0.10	5.10±0.30	4.90±0.10	5.20±0.20	4.95±0.40
模型组	6	4.90±0.40	15.00±1.00	16.00±2.00	17.00±3.00	19.00±2.00	18.00±1.00	20.00±4.00
t值	?	0.39	16.76	9.51	6.84	12.20	21.74	6.48
P值	?	0.72	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01
分组	只数	7周	8周	9周	10周	11周	12周
对照组	3	4.85±0.30	4.75±0.20	4.70±0.10	4.60±0.20	4.90±0.30	4.86±0.25
模型组	6	21.00±5.00	22.00±3.00	21.00±2.00	20.00±4.00	19.00±2.00	18.00±1.00
t值	?	5.58	9.94	14.10	6.66	12.08	22.08
P值	?	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01

表1 经高糖高脂喂养后2组猕猴0 ~ 6周空腹血糖的结果（mmol/L， ± s）

分组	只数	0周	1周	2周	3周	4周	5周	6周
对照组	3	4.80±0.20	4.90±0.30	5.00±0.10	5.10±0.30	4.90±0.10	5.20±0.20	4.95±0.40
模型组	6	4.90±0.40	15.00±1.00	16.00±2.00	17.00±3.00	19.00±2.00	18.00±1.00	20.00±4.00
t值	?	0.39	16.76	9.51	6.84	12.20	21.74	6.48
P值	?	0.72	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01
分组	只数	7周	8周	9周	10周	11周	12周
对照组	3	4.85±0.30	4.75±0.20	4.70±0.10	4.60±0.20	4.90±0.30	4.86±0.25
模型组	6	21.00±5.00	22.00±3.00	21.00±2.00	20.00±4.00	19.00±2.00	18.00±1.00
t值	?	5.58	9.94	14.10	6.66	12.08	22.08
P值	?	<0.01	<0.01	<0.01	<0.01	<0.01	<0.01

图2 经huMSCs治疗后3组猕猴空腹血糖结果比较

表2 经huMSCs治疗后3组猕猴空腹血糖的结果（mmol/L， ± s）

分组	只数	1周	2周	3周	4周
对照组	3	4.65±0.20	4.75±0.30	4.80±0.40	4.85±0.35
模型组	3	22.90±4.00^a	18.90±3.00^a	19.80±2.00^a	18.20±1.00^a
治疗组	3	19.70±1.00^a	13.40±0.8^ab	7.50±0.90^ab	4.09±0.50^b
F值	?	50.16	47.07	115.77	388.10
P值	?	<0.01	<0.01	<0.01	<0.01

表2 经huMSCs治疗后3组猕猴空腹血糖的结果（mmol/L， ± s）

分组	只数	1周	2周	3周	4周
对照组	3	4.65±0.20	4.75±0.30	4.80±0.40	4.85±0.35
模型组	3	22.90±4.00^a	18.90±3.00^a	19.80±2.00^a	18.20±1.00^a
治疗组	3	19.70±1.00^a	13.40±0.8^ab	7.50±0.90^ab	4.09±0.50^b
F值	?	50.16	47.07	115.77	388.10
P值	?	<0.01	<0.01	<0.01	<0.01

图3 光学显微镜下观察两组猕猴肺、肝脏、脾脏、肾脏、心脏、胰腺病理切片（HE染色，×100)

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