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Regenerative medicine and cell-based approaches to restore pancreatic function
Nature Reviews Gastroenterology & Hepatology ( IF 45.9 ) Pub Date : 2017-08-16 , DOI: 10.1038/nrgastro.2017.93
Cara Ellis , Adam Ramzy , Timothy J. Kieffer

The pancreas is a complex organ with exocrine and endocrine components. Many pathologies impair exocrine function, including chronic pancreatitis, cystic fibrosis and pancreatic ductal adenocarcinoma. Conversely, when the endocrine pancreas fails to secrete sufficient insulin, patients develop diabetes mellitus. Pathology in either the endocrine or exocrine pancreas results in devastating economic and personal consequences. The current standard therapy for treating patients with type 1 diabetes mellitus is daily exogenous insulin injections, but cell sources of insulin provide superior glycaemic regulation and research is now focused on the goal of regenerating or replacing β cells. Stem-cell-based models might be useful to study exocrine pancreatic disorders, and mesenchymal stem cells or secreted factors might delay disease progression. Although the standards that bioengineered cells must meet before being considered as a viable therapy are not yet established, any potential therapy must be acceptably safe and functionally superior to current therapies. Here, we describe progress and challenges in cell-based methods to restore pancreatic function, with a focus on optimizing the site for cell delivery and decreasing requirements for immunosuppression through encapsulation. We also discuss the tools and strategies being used to generate exocrine pancreas and insulin-producing β-cell surrogates in situ and highlight obstacles to clinical application.



中文翻译:

再生医学和基于细胞的方法来恢复胰腺功能

胰腺是具有外分泌和内分泌成分的复杂器官。许多病理损害外分泌功能,包括慢性胰腺炎,囊性纤维化和胰腺导管腺癌。相反,当内分泌胰腺无法分泌足够的胰岛素时,患者会患上糖尿病。内分泌或外分泌胰腺的病理学导致毁灭性的经济和个人后果。当前用于治疗1型糖尿病患者的标准疗法是每天外源性胰岛素注射,但是胰岛素的细胞来源可提供出色的血糖调节,并且目前的研究集中在再生或替代β细胞的目标上。基于干细胞的模型可能对研究外分泌型胰腺疾病有用,而间充质干细胞或分泌因子可能会延迟疾病进展。尽管尚未确立生物工程细胞在被视为可行疗法之前必须满足的标准,但是任何潜在疗法都必须在可接受的安全性和功能上优于目前的疗法。在这里,我们描述了基于细胞的方法来恢复胰腺功能的进展和挑战,重点是优化细胞递送位点并通过封装降低免疫抑制的要求。我们还将讨论用于产生外分泌胰腺和产生胰岛素的β细胞替代物的工具和策略 我们描述了基于细胞的方法来恢复胰腺功能的进展和挑战,重点是优化细胞递送位点并通过封装降低免疫抑制的要求。我们还将讨论用于产生外分泌胰腺和产生胰岛素的β细胞替代物的工具和策略 我们描述了基于细胞的方法来恢复胰腺功能的进展和挑战,重点是优化细胞递送位点并通过封装降低免疫抑制的要求。我们还将讨论用于产生外分泌胰腺和产生胰岛素的β细胞替代物的工具和策略原位并突出临床应用的障碍。

更新日期:2017-08-31
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