Street Cale N, Sipione Simonetta, Helms Lisa, Binette Tanya, Rajotte Ray V, Bleackley R Chris, Korbutt Gregory S
Surgical-Medical Research Institute, University of Alberta, Room 1074, Dentistry/Pharmacy Building, Edmonton, Alta., Canada T6G 2N8.
Int J Biochem Cell Biol. 2004 Apr;36(4):667-83. doi: 10.1016/j.biocel.2003.09.005.
Type 1 diabetes is a debilitating condition, affecting millions worldwide, that is characterized by the autoimmune destruction of insulin-producing pancreatic islets of Langerhans. Although exogenous insulin administration has traditionally been the mode of treatment for this disease, recent advancements in the transplantation of donor-derived insulin-producing cells have provided new hope for a cure. However, in order for islet transplantation to become a widely used technique, an alternative source of cells must be identified to supplement the limited supply currently available from cadaveric donor organs. Stem cells represent a promising solution to this problem, and current research is being aimed at the creation of islet-endocrine tissue from these undifferentiated cells. This review presents a summary of the research to date involving stem cells and cell replacement therapy for type 1 diabetes. The potential for the differentiation of embryonic stem (ES) cells to islet phenotype is discussed, as well as the possibility of identifying and exploiting a pancreatic progenitor/stem cell from the adult pancreas. The possibility of creating new islets from adult stem cells derived from other tissues, or directly form other terminally differentiated cell types is also addressed. Finally, a model for the isolation and maturation of islets from the neonatal porcine pancreas is discussed as evidence for the existence of an islet precursor cell in the pancreas.
1型糖尿病是一种使人衰弱的疾病,影响着全球数百万人,其特征是胰岛β细胞被自身免疫破坏,胰岛β细胞可产生胰岛素。虽然传统上一直采用外源性胰岛素给药来治疗这种疾病,但供体来源的胰岛素生成细胞移植方面的最新进展为治愈该病带来了新希望。然而,为了使胰岛移植成为一种广泛应用的技术,必须找到替代细胞来源,以补充目前来自尸体供体器官的有限供应。干细胞是解决这一问题的一个有前景的办法,目前的研究旨在从这些未分化细胞中培育出胰岛内分泌组织。本综述总结了迄今为止有关1型糖尿病干细胞及细胞替代疗法的研究。讨论了胚胎干细胞分化为胰岛表型的可能性,以及从成年胰腺中识别和利用胰腺祖细胞/干细胞的可能性。还探讨了从其他组织来源的成体干细胞或直接从其他终末分化细胞类型生成新胰岛的可能性。最后,讨论了从新生猪胰腺中分离和成熟胰岛的模型,以此作为胰腺中存在胰岛前体细胞的证据。