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骨髓间充质干细胞与胰岛共移植对受体小鼠骨髓来源树突状细胞成熟及功能的影响

[The effect of co-transplantation of bone marrow-derived mesenchymal stem cells and islet on maturation and function of bone marrow-derived dendritic cells in recipient mice].

作者信息

Li Fu-rong, Deng Chun-yan, Wang Xin-gen, Qi Hui, Ren Li-li, Zhou Han-xin

机构信息

Clinical Medical Research Center, the 2nd Clinical Medical College, Shenzhen Peoples Hospital, Jinan University, Shenzhen 518020, China.

出版信息

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2010 Jul;26(7):646-9.

PMID:20619087
Abstract

AIM

To investigate the effect of transplantation of bone marrow-derived mesenchymal stem cells (MSCs), or co-transplantation of islet and MSCs, on maturation and function of bone marrow-derived dendritic cells (DCs) in recipient mice.

METHODS

Bone marrow MSCs were isolated from BALB/c mice and co-cultured with bone marrow mononuclear cells (BMCs) from C57BL/6 mice at indicated ratios. The co-cultures were treated with recombinant mice granulocyte-macro-phage colony-stimulating factor (rmGM-CSF) and recombinant mice IL-4 (rmIL-4) for 7 days to induce the differentiation of DCs, with lipopolysaccharide (LPS) favoring the maturation of DCs. The differentiation markers and antigen uptake capability of DCs were analyzed by FCM. Production of Interleukin-12 in the supernatants of the DC cultures was quantified by ELISA. BALB/c-derived MSCs and islet were co-transplanted to the capsule of kidney in allogeneic C57BL/c mice. The recipient mice were assayed for their tissue morphology, blood glucose level, and the in vitro differentiation ability of their BMC into mature and functional DCs.

RESULTS

The transplantation of MSCs prevented BMC from differentiating into mature DCs, as shown by down-regulated surface markers of DCs including CD11c, CD83, CD86 and I-Ab; (P<0.05), impaired antigen uptake and decreased IL-12 secretion (P<0.01). Co-transplantation of MSCs and islet inhibited immune rejection in the allogeneic recipient mice.

CONCLUSION

Transplantation of MSCs inhibits maturation and function of monocyte-derived dendritic cells in the recipient mice, resulting in immune tolerance for the allogeneic islet.

摘要

目的

研究骨髓间充质干细胞(MSCs)移植或胰岛与MSCs共移植对受体小鼠骨髓来源树突状细胞(DCs)成熟及功能的影响。

方法

从BALB/c小鼠分离骨髓MSCs,并与C57BL/6小鼠的骨髓单个核细胞(BMCs)按指定比例共培养。共培养物用重组小鼠粒细胞-巨噬细胞集落刺激因子(rmGM-CSF)和重组小鼠白细胞介素-4(rmIL-4)处理7天以诱导DCs分化,脂多糖(LPS)促进DCs成熟。通过流式细胞术分析DCs的分化标志物和抗原摄取能力。用酶联免疫吸附测定法对DC培养上清液中的白细胞介素-12产量进行定量。将BALB/c来源的MSCs和胰岛共移植到同种异体C57BL/c小鼠的肾被膜下。对受体小鼠进行组织形态学、血糖水平以及其BMC体外分化为成熟且有功能的DCs能力的检测。

结果

MSCs移植可阻止BMC分化为成熟DCs,表现为DCs表面标志物包括CD11c、CD83、CD86和I-Ab下调(P<0.05),抗原摄取受损以及白细胞介素-12分泌减少(P<0.01)。MSCs与胰岛共移植可抑制同种异体受体小鼠的免疫排斥反应。

结论

MSCs移植可抑制受体小鼠单核细胞来源树突状细胞的成熟及功能,从而导致对同种异体胰岛的免疫耐受。

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