Regeneration of insulin-producing pancreatic cells using a volatile bioactive compound and human teeth
Regeneration of insulin-producing pancreatic cells using a volatile bioactive compound and human teeth
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使用挥发性生物活性化合物和人类牙齿再生产生胰岛素的胰腺细胞
DOI：
10.1088/1752-7155/8/4/046004
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Tanaka T
中科院分区：
文献类型：
--
作者：
Okada M;Imai T;Yaegaki K;Ishkitiev N;Tanaka T
从干细胞体外分化的胰岛素分泌细胞的移植有望更安全和更容易地治疗严重的糖尿病。一种挥发性的生物活性化合物，硫化氢（H2S），促进细胞分化;人类牙髓干细胞经历肝分化。本研究的目的是开发一种新的方案，使用H2S，以促进胰腺分化的CD 117+细胞的人牙髓部分。在分化过程中，将细胞暴露于0.1 ng ml− 1 H2 S。采用免疫细胞化学、RT-PCR、INS C肽含量测定和流式细胞术检测胰腺相关标志物。PCR芯片检测WNT和PI 3 K/AKT信号通路的表达。分化后免疫荧光检测INS、胰高血糖素（GCG）、生长抑素（SST）和胰多肽（PPY）均为阳性。INS和GCG也通过流式细胞术测定。H2S暴露后，只有INS表达增加.表达GCG的细胞数量显著减少。典型WNT和WNT/钙通道相关基因在H2S暴露后高度表达。H2S可促进人牙INS产生细胞合成和分泌INS。H2S暴露后，PI 3 K-AKT通路的所有信号通路功能均被激活。利用H2S刺激人牙齿中成熟的INS分泌细胞，以达到控制血糖的目的。
Transplantation of insulin (INS)-secreting cells differentiated in vitro from stem cells promises a safer and easier treatment of severe diabetes mellitus. A volatile bioactive compound, hydrogen sulfide (H 2 S), promotes cell differentiation; human tooth-pulp stem cells undergo hepatic differentiation. The aim of this study is to develop a novel protocol using H 2 S to enhance pancreatic differentiation from the CD117+ cell fraction of human tooth pulp. During the differentiation, the cells were exposed to 0.1 ng ml− 1 H 2 S. Immunocytochemistry, RT-PCR, determination of INS c-peptide content and flow cytometry of pancreatically related markers were carried out. Expression of WNT and the PI3K/AKT signaling pathway were also determined by PCR array. After differentiation, INS, glucagon (GCG), somatostatin (SST) and pancreatic polypeptide (PPY) were positive when examined by immunofluorescence. INS and GCG were also determined flow-cytometrically. Only the cells expressing INS increased after H 2 S exposure. The number of cells expressing GCG was significantly decreased. Genes involved in canonical WNT and the WNT/calcium pathways were highly expressed after H 2 S exposure. H 2 S accelerated INS synthesis and secretion by regenerated INS-producing cells from human teeth. All signaling pathway functions of the PI3K-AKT pathway were extremely activated by H 2 S exposure. The matured INS-producing cells originating in human teeth were increased by H 2 S in order to control blood-glucose level.
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