The Differences in the Characteristics of Insulin-producing Cells Using Human Adipose-tissue Derived Mesenchymal Stem Cells from Subcutaneous and Visceral Tissues
The Differences in the Characteristics of Insulin-producing Cells Using Human Adipose-tissue Derived Mesenchymal Stem Cells from Subcutaneous and Visceral Tissues
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DOI：
10.1038/s41598-019-49701-0
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发表时间：
2019-09-13
影响因子：
4.6
通讯作者：
Shimada, Mitsuo
中科院分区：
文献类型：
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作者：
Wada, Yuma;Ikemoto, Tetsuya;Shimada, Mitsuo
本研究的目的是研究从人皮下和内脏脂肪组织中分离的脂肪组织源干细胞(ADSCs)向胰岛素产生细胞(IPC)分化的特性，并寻找适合于分化为高效和功能IPC的ADSCs。皮下和内脏脂肪组织收集自德岛大学(000035546)接受消化手术的四(4)名患者(000035546)。通过荧光激活细胞分选(FACS)分析、细胞因子释放、ADSCs的增殖能力、体外(葡萄糖刺激的胰岛素分泌：GSIS)试验/体内(移植到链脲佐菌素诱导的糖尿病裸鼠体内)检测所生成的IPC的胰岛素分泌。脂肪相关炎性细胞因子分泌较少(P<；0.05)，增殖能力较高(P<；0.05)。皮下IPC的胰岛素表达和GISI较高(P<；0.01和P<；0.05)。从皮下脂肪组织接受IPC的所有小鼠在移植后30(30)天内高血糖状态转变为正常血糖(4/4,100%)。用抗胰岛素和抗人白细胞抗原抗体对移植的IPC进行染色。从新鲜分离的人脂肪组织中分离出的脂肪干细胞在体外和体内都具有足够的胰岛素分泌能力。
The aim of this study was to investigate the characteristics of insulin producing cells (IPCs) differentiated from adipose-tissue derived stem cells (ADSCs) isolated from human subcutaneous and visceral adipose tissues and identify ADSCs suitable for differentiation into efficient and functional IPCs. Subcutaneous and visceral adipose tissues collected from four (4) patients who underwent digestive surgeries at The Tokushima University (000035546) were included in this study. The insulin secretion of the generated IPCs was investigated using surface markers by: fluorescence activated cell sorting (FACS) analysis; cytokine release; proliferation ability of ADSCs; in vitro (glucose-stimulated insulin secretion: (GSIS) test/in vivo (transplantation into streptozotocin-induced diabetic nude mice). The less fat-related inflammatory cytokines secretions were observed (P < 0.05), and the proliferation ability was higher in the subcutaneous ADSCs (P < 0.05). Insulin expression and GISI were higher in the subcutaneous IPCs (P < 0.01 and P < 0.05, respectively). The hyperglycaemic state of all mice that received IPCs from subcutaneous fat tissue converted into normo-glycaemia in thirty (30) days post-transplantation (4/4,100%). Transplanted IPCs were stained using anti-insulin and anti-human leukocyte antigen antibodies. The IPCs generated from the ADSCs freshly isolated from the human fat tissue had sufficient insulin secreting ability in vitro and in vivo.