The influence of adipose mesenchymal stem cell on immune status and transplantation effect when co-transplanted with allogenic islet

doi:10.3877/cma.j.issn.1674-3903.2019.02.012

Abstract

Abstract:

Objective

To investigate the influence of adipose mesenchymal stem cell (AMSC) on immune status and transplantation effect when co-transplanted with allogenic islets.

Methods

The streptozotocin induced diabetic Lewis rats were selected as islet transplantation recipients. The diabetic rats which were co-transplanted with islets from Wistar rats and AMSC from Lewis rats were set as the AMSC+ islet transplantation group. The rats in islet transplantation group were transplanted with islets from Wistar rats. The rats in AMSC transplantation group were transplanted with AMSC from Lewis rats. All the islets and AMSC were transplanted through subrenal capsular of left kidney. The rats in positive control group were diabetic Lewis rats. The rats in negtive control group were normal Lewis rats. The concentrations of IFN-γ, IL-2, IL-4 and IL-10 in peripheraI blood serum was detected with ELISA, the average percentage of CD4⁺ T and CD8⁺ T cells in peripheral blood was tested with flow cytometry, the infiltration of lymphocytes in the islets grafts was observed by HE staining. Blood glucose and serum insulin levels of the rats and survival time of the islet grafts were observed.

Results

The mean survival time of the islet grafts was longer in AMSC+ islet transplantation group [(26.8±3.0) days] than in islet transplantation group [(19.0±1.3) days], and statistical differences was also found for survival curve of islets grafts between the two groups (χ²=4.494, P<0.05). The blood glucose and serum insulin levels of the diabetic rats in the AMSC+ islet transplantation group were better than those in the islet transplantation group at different time points after transplantation (P all <0.05). Before islets transplantation, there were no statistical differences for the indexes including the average percentage of peripheral blood CD4⁺ T, CD8⁺ T cells and serum concentrations of IFN-γ, IL-2, IL-4 and IL-10 among the 5 groups (F=0.425, 0.476, 0.256, 0.418, 0.281, 0.313, P all >0.05). On the 7th, 14th and 28th days after transplantation, the serum concentrations of IFN-γ and IL-2 in the AMSC+ islet transplantation group were significantly lower than those in the islet transplantation group (P all <0.05), and the serum concentrations of IL-4 and IL-10 significantly higher than those in the islet transplantation group (P all <0.05), the average percentage of peripheral blood CD4⁺ T and CD8⁺ T cells less than those in the islet transplantation group (P all <0.05). On the 7th day after transplantation, the infiltrating lymphocyte counts of islet grafts in the AMSC+ islet transplantation group were significantly lower than those in the islet transplantation group (t=8.245, P<0.05).

Conclusions

In diabetic rats, AMSC could improve the effects of islets transplantation, regulate the expression of IFN-γ, IL-2, IL-4 and IL-10, suppress the T lymphocyte proliferation, and reduce islet grafts immune injury.

Key words: Adipose mesenchymal stem cell, Islet transplantation, Rejection, Diabetes mellitus, Co-transplant, Rats

Zizhao Jiao, Wujun Xue, Fenglou Li, Yang Li, Zuohua Zhang, xiu Li, Maozhu An. The influence of adipose mesenchymal stem cell on immune status and transplantation effect when co-transplanted with allogenic islet[J]. Chinese Journal of Transplantation(Electronic Edition), 2019, 13(02): 135-140.

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Figures/Tables 6

References 24

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组别	例数	CD4^＋T细胞比例				CD8^＋T细胞比例
		移植前	移植后			移植前	移植后
		移植前	第7天	第14天	第28天	移植前	第7天	第14天	第28天
AMSC＋胰岛移植组	6	36.6±4.0	42.3±4.2^a	43.2±4.3^a	42.9±4.1^a	28.6±2.7	32.3±4.0^a	33.4±3.6^a	32.9±3.8^a
单纯胰岛移植组	6	38.4±4.0	56.5±6.1	57.0±5.8	56.9±5.8	29.7±2.5	45.6±5.1	47.8±5.3	47.0±5.2
单纯AMSC移植组	6	37.3±3.3	37.8±4.2^a	38.1±3.6^a	37.6±4.3^a	28.3±2.7	27.3±2.9^a	28.7±2.8^a	29.0±3.2^a
阳性对照组	6	37.4±3.7	36.7±4.2^a	38.1±3.8^a	37.2±4.1^a	28.1±2.8	28.3±2.7^a	29.2±3.0^a	28.4±3.1^a
阴性对照组	6	36.9±3.9	38.4±4.0^a	37.0±4.2^a	38.4±4.3^a	29.2±3.1	28.7±3.2^a	29.5±3.5^a	28.9±3.8^a

组别	例数	CD4^＋T细胞比例				CD8^＋T细胞比例
		移植前	移植后			移植前	移植后
		移植前	第7天	第14天	第28天	移植前	第7天	第14天	第28天
AMSC＋胰岛移植组	6	36.6±4.0	42.3±4.2^a	43.2±4.3^a	42.9±4.1^a	28.6±2.7	32.3±4.0^a	33.4±3.6^a	32.9±3.8^a
单纯胰岛移植组	6	38.4±4.0	56.5±6.1	57.0±5.8	56.9±5.8	29.7±2.5	45.6±5.1	47.8±5.3	47.0±5.2
单纯AMSC移植组	6	37.3±3.3	37.8±4.2^a	38.1±3.6^a	37.6±4.3^a	28.3±2.7	27.3±2.9^a	28.7±2.8^a	29.0±3.2^a
阳性对照组	6	37.4±3.7	36.7±4.2^a	38.1±3.8^a	37.2±4.1^a	28.1±2.8	28.3±2.7^a	29.2±3.0^a	28.4±3.1^a
阴性对照组	6	36.9±3.9	38.4±4.0^a	37.0±4.2^a	38.4±4.3^a	29.2±3.1	28.7±3.2^a	29.5±3.5^a	28.9±3.8^a

组别	例数	IFN-γ				IL-2
		移植前	移植后			移植前	移植后
		移植前	第7天	第14天	第28天	移植前	第7天	第14天	第28天
AMSC＋胰岛移植组	6	78±7	103±10^a	115±14^a	108±12^a	108±19	341±27^a	358±30^a	349±28^a
单纯胰岛移植组	6	80±8	342±16	362±15	356±16	118±22	868±39	1160±43	1088±42
单纯AMSC移植组	6	79±9	80±10^a	80± 9^a	79±11^a	109±17	107±21^a	110±20^a	108±18^a
阳性对照组	6	78±8	79± 7^a	77± 8^a	79± 9^a	105±18	109±20^a	108±19^a	107±18^a
阴性对照组	6	80±9	80± 6^a	81± 7^a	80± 8^a	113±21	119±19^a	109±22^a	118±21^a
组别	例数	IL-4				IL-10
		移植前	移植后			移植前	移植后
		移植前	第7天	第14天	第28天	移植前	第7天	第14天	第28天
AMSC＋胰岛移植组	6	19.3±1.9	32.8±2.9	48.2±3.7	73.5±4.7	24.6±2.5	47.3±3.8	71.2±4.0	75.8±4.6
单纯胰岛移植组	6	20.0±1.7	26.4±2.1^b	28.3±1.8^b	32.4±2.1^b	22.8±2.3	27.2±2.0^b	28.8±2.0^b	34.8±2.0^b
单纯AMSC移植组	6	20.4±2.0	19.7±1.9^b	21.4±2.2^b	24.2±1.9^b	23.6±2.3	24.8±2.8^b	24.9±3.0^b	23.8±2.8^b
阳性对照组	6	20.6±1.9	20.6±2.1^b	21.1±2.3^b	21.9±2.1^b	23.9±2.2	25.3±2.6^b	24.9±2.4^b	24.0±2.7^b
阴性对照组	6	19.8±1.8	21.5±1.7^b	22.3±2.0^b	21.6±1.8^b	22.8±2.2	23.4±2.1^b	24.0±2.2^b	22.3±2.3^b

组别	例数	IFN-γ				IL-2
		移植前	移植后			移植前	移植后
		移植前	第7天	第14天	第28天	移植前	第7天	第14天	第28天
AMSC＋胰岛移植组	6	78±7	103±10^a	115±14^a	108±12^a	108±19	341±27^a	358±30^a	349±28^a
单纯胰岛移植组	6	80±8	342±16	362±15	356±16	118±22	868±39	1160±43	1088±42
单纯AMSC移植组	6	79±9	80±10^a	80± 9^a	79±11^a	109±17	107±21^a	110±20^a	108±18^a
阳性对照组	6	78±8	79± 7^a	77± 8^a	79± 9^a	105±18	109±20^a	108±19^a	107±18^a
阴性对照组	6	80±9	80± 6^a	81± 7^a	80± 8^a	113±21	119±19^a	109±22^a	118±21^a
组别	例数	IL-4				IL-10
		移植前	移植后			移植前	移植后
		移植前	第7天	第14天	第28天	移植前	第7天	第14天	第28天
AMSC＋胰岛移植组	6	19.3±1.9	32.8±2.9	48.2±3.7	73.5±4.7	24.6±2.5	47.3±3.8	71.2±4.0	75.8±4.6
单纯胰岛移植组	6	20.0±1.7	26.4±2.1^b	28.3±1.8^b	32.4±2.1^b	22.8±2.3	27.2±2.0^b	28.8±2.0^b	34.8±2.0^b
单纯AMSC移植组	6	20.4±2.0	19.7±1.9^b	21.4±2.2^b	24.2±1.9^b	23.6±2.3	24.8±2.8^b	24.9±3.0^b	23.8±2.8^b
阳性对照组	6	20.6±1.9	20.6±2.1^b	21.1±2.3^b	21.9±2.1^b	23.9±2.2	25.3±2.6^b	24.9±2.4^b	24.0±2.7^b
阴性对照组	6	19.8±1.8	21.5±1.7^b	22.3±2.0^b	21.6±1.8^b	22.8±2.2	23.4±2.1^b	24.0±2.2^b	22.3±2.3^b

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