Human adipose-derived stromal/stem cells protect against STZ-induced hyperglycemia: analysis of hASC-derived paracrine effectors.
Human adipose-derived stromal/stem cells protect against STZ-induced hyperglycemia: analysis of hASC-derived paracrine effectors.
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人脂肪衍生的基质/干细胞可预防STZ诱导的高血糖：HASC衍生的旁分泌效应子的分析。
DOI：
10.1002/stem.1676
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发表时间：
2014-07
期刊：
影响因子：
5.2
通讯作者：
Evans-Molina, Carmella
中科院分区：
文献类型：
--
作者：
Kono, Tatsuyoshi M.;Sims, Emily K.;Moss, Dan R.;Yamamoto, Wataru;Ahn, Geonyoung;Diamond, Julie;Tong, Xin;Day, Kathleen H.;Territo, Paul R.;Hanenberg, Helmut;Traktuev, Dmitry O.;March, Keith L.;Evans-Molina, Carmella
脂肪源性基质/干细胞 (ASC) 可改善胰岛移植和自身免疫性糖尿病啮齿动物模型中的高血糖，但导致这些作用的精确人类 ASC (hASC) 衍生因子在很大程度上仍未被探索。在这里，我们表明，全身给予 hASC 可改善 STZ 治疗的 NOD-SCID 小鼠的葡萄糖耐量、保留 β 细胞质量并增加 β 细胞增殖。小鼠或人胰岛与 hASC 的共培养实验表明，经过长时间培养或用促炎细胞因子处理后，hASC 可以改善胰岛的活力和功能。对 hASC 衍生因子的分析表明 VEGF 和 TIMP-1 是 hASC 分泌的高度丰富的因子。值得注意的是，在细胞因子治疗产生的胰岛应激下，TIMP-1 分泌增加，而 TIMP-1 阻断能够消除 hASC 的体外促生存作用。通过尾静脉注射全身给药后，在胰腺中检测到 hASC，并且注射小鼠血清中的人 TIMP-1 增加，而重组 TIMP-1 增加了用 IL-1β、IFN-γ 和 TNF-α 处理的 INS-1 细胞的活力。总的来说，我们的数据支持一个模型，即 hASC 分泌的因子（例如 TIMP-1）能够通过局部旁分泌和全身效应的结合，减轻啮齿动物和 1 型糖尿病体外模型中的 β 细胞死亡。
Adipose-derived stromal/stem cells (ASCs) ameliorate hyperglycemia in rodent models of islet transplantation and autoimmune diabetes, yet the precise human ASC (hASC)-derived factors responsible for these effects remain largely unexplored. Here, we show that systemic administration of hASCs improved glucose tolerance, preserved β cell mass, and increased β cell proliferation in STZ-treated NOD-SCID mice. Co-culture experiments combining mouse or human islets with hASCs demonstrated that islet viability and function were improved by hASCs following prolonged culture or treatment with pro-inflammatory cytokines. Analysis of hASC-derived factors revealed VEGF and TIMP-1 to be highly abundant factors secreted by hASCs. Notably, TIMP-1 secretion increased in the presence of islet stress from cytokine treatment, while TIMP-1 blockade was able to abrogate in vitro pro-survival effects of hASCs. Following systemic administration by tail vein injection, hASCs were detected in the pancreas and human TIMP-1 was increased in the serum of injected mice, while recombinant TIMP-1 increased viability in INS-1 cells treated with IL-1β, IFN-γ and TNF-α. In aggregate, our data support a model whereby factors secreted by hASCs, such as TIMP-1, are able to mitigate against β cell death in rodent and in vitro models of Type 1 diabetes through a combination of local paracrine as well as systemic effects.
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影响因子：
3.7
作者：
Chandra V;Swetha G;Muthyala S;Jaiswal AK;Bellare JR;Nair PD;Bhonde RR
通讯作者：
Bhonde RR
影响因子：
3.7
作者：
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通讯作者：
Xiong L
DOI：
10.1073/pnas.0608249103
发表时间：
2006-11-14
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
4.8
作者：
Kang, Soojeong;Park, Eun-Jin;Lee, Hye-Jeong
通讯作者：
Lee, Hye-Jeong