Transplantation of islet-like cell clusters derived from human dental pulp stem cells restores normoglycemia in diabetic mice

Transplantation of islet-like cell clusters derived from human dental pulp stem cells restores normoglycemia in diabetic mice
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DOI:
10.1016/j.jcyt.2013.05.008
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发表时间:
2013-10-01
期刊:
影响因子:
4.5
通讯作者:
Bhonde, Ramesh Ramchandra
Bhonde, Ramesh Ramchandra
中科院分区:
医学3区
文献类型:
--
作者:
Kanafi, Mohammad Mahboob;Rajeshwari, Yajaman Bajjappa;Bhonde, Ramesh Ramchandra

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背景的目标。胰岛移植治疗糖尿病的成功与否取决于是否有足够数量的异体或自体胰岛。现在认为,产后干细胞可以产生具有生理能力的胰岛素生成细胞。我们的研究小组早些时候表明,通过在三步方案中使用无血清鸡尾酒,可以从人类牙髓干细胞中产生功能性胰岛。方法。我们比较了从人脱落乳牙(SHED)和恒牙(DPSCs)的牙髓干细胞中提取的胰岛样细胞团(ICCs)的产量。从SHED中获得的icc被包装在免疫分离的生物相容性大胶囊中,并移植到链脲佐菌素(STZ)诱导的糖尿病小鼠中。非糖尿病和糖尿病对照组分别移植有或没有胰岛的大胶囊。结果。SHED优于DPSCs。单独的STZ糖尿病小鼠和空移植小鼠在整个实验过程中都表现出高血糖,而移植含有icc的大胶囊小鼠在3-4周内恢复到正常血糖,并持续50 - 60天。结论。我们的研究结果首次证明,来自SHED的ICCs在没有免疫抑制的情况下逆转小鼠STZ糖尿病,并提供了一种可用于糖尿病干细胞治疗的自体和无争议的人体组织来源。
Background aims. The success of islet transplantation for diabetes depends on the availability of an adequate number of allogeneic or autologous islets. Postnatal stem cells are now considered for the generation of physiologically competent, insulin-producing cells. Our group showed earlier that it is possible to generate functional islets from human dental pulp stem cells by using a serum-free cocktail in a three-step protocol. Methods. We compared the yield of generated islet-like cell clusters (ICCs) from stem cells from pulps of human exfoliated deciduous teeth (SHED) and dental pulp stem cells from permanent teeth (DPSCs). ICCs derived from SHED were packed in immuno-isolatory biocompatible macro-capsules and transplanted into streptozotocin (STZ)-induced diabetic mice. Non-diabetic and diabetic controls were transplanted with macro-capsules with or without islets. Results. SHED were superior to DPSCs. STZ diabetic mice alone and mice transplanted with empty exhibited hyperglycemia throughout the experiment, whereas mice transplanted with macro-capsules containing ICCs were restored to normoglycemia within 3-4 weeks, which persisted for >60 days. Conclusions. Our results demonstrate for the first time that ICCs derived from SHED reverse STZ diabetes in mice without immunosuppression and offer an autologous and non-controversial source of human tissue that could be used for stem cell therapy in diabetes.