Human Umbilical Cord Blood Mesenchymal Stem Cell-Derived PGE2 and TGF-β1 Alleviate Atopic Dermatitis by Reducing Mast Cell Degranulation
Human Umbilical Cord Blood Mesenchymal Stem Cell-Derived PGE2 and TGF-β1 Alleviate Atopic Dermatitis by Reducing Mast Cell Degranulation
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DOI：
10.1002/stem.1913
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发表时间：
2015-04-01
期刊：
影响因子：
5.2
通讯作者：
Kang, Kyung-Sun
中科院分区：
文献类型：
--
作者：
Kim, Hyung-Sik;Yun, Jun-Won;Kang, Kyung-Sun
间充质干细胞（MSC）是治疗免疫性疾病的一种有前途的工具。然而，它们在治疗过敏性皮肤疾病中的功效和机制较少被证实。我们试图研究人脐带血来源的间充质干细胞（hUCB-MSCs）对小鼠特应性皮炎（AD）的治疗效果，并探索调节其疗效的不同机制。通过局部应用粉尘螨在小鼠中诱导AD。向小鼠施用未处理或活化的hUCB-MSC，并确定临床严重程度。皮下注射核苷酸结合寡聚化结构域2（NOD 2）激活的hUCB-MSCs对AD表现出显著的保护作用，并抑制肥大细胞（MC）的浸润和脱粒。进行α-氨基己糖苷酶测定以评估hUCB-MSC对MC脱粒的影响。NOD 2激活的MSC通过NOD 2-环氧合酶-2信号转导减少MC脱颗粒。与骨髓来源的MSC相比，hUCB-MSC通过更高的前列腺素E-2（PGE（2））产生对MC脱粒产生细胞-细胞接触非依赖性抑制作用。此外，hUCB-MSC对白细胞介素-4的反应产生转化生长因子（TGF）-1，通过下调MC中Fc β RI的表达，有助于MC脱粒的减弱。结论：NOD 2激活的hUCB-MSCs皮下应用可有效改善AD，MSCs来源的PGE（2）和TGF-1是抑制MC脱颗粒的必要条件。干细胞2015;33：1254-1266
Mesenchymal stem cell (MSC) is a promising tool for the therapy of immune disorders. However, their efficacy and mechanisms in treating allergic skin disorders are less verified. We sought to investigate the therapeutic efficacy of human umbilical cord blood-derived MSCs (hUCB-MSCs) against murine atopic dermatitis (AD) and to explore distinct mechanisms that regulate their efficacy. AD was induced in mice by the topical application of Dermatophagoides farinae. Naive or activated-hUCB-MSCs were administered to mice, and clinical severity was determined. The subcutaneous administration of nucleotide-binding oligomerization domain 2 (NOD2)-activated hUCB-MSCs exhibited prominent protective effects against AD, and suppressed the infiltration and degranulation of mast cells (MCs). A -hexosaminidase assay was performed to evaluate the effect of hUCB-MSCs on MC degranulation. NOD2-activated MSCs reduced the MC degranulation via NOD2-cyclooxygenase-2 signaling. In contrast to bone marrow-derived MSCs, hUCB-MSCs exerted a cell-to-cell contact-independent suppressive effect on MC degranulation through the higher production of prostaglandin E-2 (PGE(2)). Additionally, transforming growth factor (TGF)-1 production from hUCB-MSCs in response to interleukin-4 contributed to the attenuation of MC degranulation by downregulating Fc epsilon RI expression in MCs. In conclusion, the subcutaneous application of NOD2-activated hUCB-MSCs can efficiently ameliorate AD, and MSC-derived PGE(2) and TGF-1 are required for the inhibition of MC degranulation. Stem Cells2015;33:1254-1266