Treating Diet-InducedDiabetes and Obesity with Human Embryonic Stem Cell-Derived PancreaticProgenitor Cells and Antidiabetic Drugs
Human embryonicstem cell (hESC)-derived pancreatic progenitor cells effectively reversehyperglycemia in rodent models of type 1 diabetes, but their capacity to treattype 2 diabetes has not been reported. An immunodeficient model of type 2diabetes was generated by high-fat diet (HFD) feeding in SCID-beige mice.Exposure to HFDs did not impact the maturation of macroencapsulated pancreaticprogenitor cells into glucose-responsive insulin-secreting cells followingtransplantation, and the cell therapy improved glucose tolerance in HFD-fedtransplant recipients after 24 weeks. However, since diet-induced hyperglycemiaand obesity were not fully ameliorated by transplantation alone, a secondcohort of HFD-fed mice was treated with pancreatic progenitor cells combinedwith one of three antidiabetic drugs. All combination therapies rapidlyimproved body weight and co-treatment with either sitagliptin or metforminimproved hyperglycemia after only 12 weeks. Therefore, a stem cell-basedtherapy may be effective for treating type 2 diabetes, particularly incombination with antidiabetic drugs.
基于干细胞移植的新型2型糖尿病疗法
发布时间：2015-03-24 00:00 文章来源： 作者：
关键词：2型糖尿病 干细胞移植
近日，来自加拿大不列颠哥伦比亚大学的研究团队试验了一种针对2型糖尿病的新治疗方案，通过结合干细胞移植技术同时给予抗糖尿病药物，对于治疗患有2型糖尿病实验鼠呈现了显著的治疗效果。该文章发表在Stem Cell Reports上。
2型糖尿病是由于人体无法产生足够量的胰岛素并且有效地利用它们，从而导致血糖水平升高。对此，为了控制血糖，病人往往需要口服药物，如二甲双胍，或者注射胰岛素，又或者两者兼用。“然而，这样的治疗方法常常会导致病人胃肠问题的发生，体重增加并导致血糖含量比正常水平还要偏低。”主持该研究的Timothy Kieffer教授说到。
图注：这张图显示的是被移植到实验鼠体内的源于人体胚胎干细胞的胰腺β细胞。（图片来源：Jennifer Bruin，不列颠哥伦比亚大学）
通过β-细胞移植提高血糖新陈代谢水平及胰岛素敏感指数
研究人员首先利用实验鼠建立了2型糖尿病疾病模型，即通过给老鼠食喂高脂肪的食物使其呈现肥胖、胰岛素低敏感性以及高血糖等症状。紧接着，研究人员将来源于人体胚胎干细胞，同时被包入胶囊的胰腺祖细胞移植到实验鼠中。胰腺祖细胞分化成为β细胞——一类在胰腺中产生胰岛素的细胞——使得实验鼠的血糖新陈代谢及对于胰岛素的敏感度同时提高。
此外，对于那些同时进行了干细胞移植并给予了抗糖尿病药物的实验鼠，其体重会迅速下降，而相较于两种治疗方法（干细胞移植、抗糖尿病药物）中的任何一种，这种双管齐下的治疗方式能够更加显著地提高血糖的新陈代谢。
如今，Kieffer教授及其团队在此基础上提出了进一步的假设，即如果将更低剂量但更成熟的β细胞（而非胰腺祖细胞）直接注射到患有2型糖尿病的实验鼠中，各个病症将得到更加快速而显著的消除。
研究人员相信，这项方法最终能够被应用到对于人体的临床试验中。值得注意的是，针对1型糖尿病，来自美国食品药品监督管理局以及加拿大卫生部的科研人员最近证实并通过了一项类似的技术，并可被应用到人体1型糖尿病治疗中。
“这些研究项目的临床意义是巨大的。我们希望基于干细胞的治疗方法将最终有助于那些患有1型或2型糖尿病的患者都能够有效地控制体内的血糖。”Kieffer教授说。
原文摘要：
Treating Diet-InducedDiabetes and Obesity with Human Embryonic Stem Cell-Derived PancreaticProgenitor Cells and Antidiabetic Drugs
Human embryonicstem cell (hESC)-derived pancreatic progenitor cells effectively reversehyperglycemia in rodent models of type 1 diabetes, but their capacity to treattype 2 diabetes has not been reported. An immunodeficient model of type 2diabetes was generated by high-fat diet (HFD) feeding in SCID-beige mice.Exposure to HFDs did not impact the maturation of macroencapsulated pancreaticprogenitor cells into glucose-responsive insulin-secreting cells followingtransplantation, and the cell therapy improved glucose tolerance in HFD-fedtransplant recipients after 24 weeks. However, since diet-induced hyperglycemiaand obesity were not fully ameliorated by transplantation alone, a secondcohort of HFD-fed mice was treated with pancreatic progenitor cells combinedwith one of three antidiabetic drugs. All combination therapies rapidlyimproved body weight and co-treatment with either sitagliptin or metforminimproved hyperglycemia after only 12 weeks. Therefore, a stem cell-basedtherapy may be effective for treating type 2 diabetes, particularly incombination with antidiabetic drugs.
（来源：Medical Research）
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