Zhang You-Qing, Sarvetnick Nora
Department of Immunology, The Scripps Research Institute, North Torrey Pines Road, La Jolla, CA 92037, USA.
Diabetes Metab Res Rev. 2003 Sep-Oct;19(5):363-74. doi: 10.1002/dmrr.406.
Diabetes mellitus results from the anatomical or functional loss of insulin-producing beta cells of the pancreas. Despite significant advances in current treatment, patients with diabetes still do not maintain optimal glucose levels and therefore face debilitating complications such as hypoglycemia, retinopathy or cardiovascular diseases later in life. Islet transplantation therefore holds great promise as an ultimate cure for diabetes. However, the shortage of availability of donor sources of islets for transplantation has largely hampered this therapy. In this respect, the use of alternative sources of islets such as the ex vivo culture and expansion and differentiation of functional endocrine cells for treating diabetes has been a major focus of diabetes research. The identity of the islet stem/progenitor cells has remained either elusive or at least equivocal because of the lack of cell markers for identification of these cells. Recent successes in studying the organogenesis of pancreas as well as in vitro islet progenitor cell identification studies have provided tremendous insight for the cell markers that are essential in the isolation and characterization of these cells prospectively both in vivo and in vitro. If we can identify the markers that will aid the isolation and purification of islet progenitor cells, or factors that determine pancreatic cell fate, we might be able to coerce them from turning into specific endocrine cells or pancreas in vitro. This article will focus on this subject and will review the latest achievements in the study of cell markers for islet progenitor cells.
糖尿病是由胰腺中产生胰岛素的β细胞在解剖学或功能上的丧失所致。尽管当前治疗取得了显著进展,但糖尿病患者仍无法维持最佳血糖水平,因此在生命后期面临诸如低血糖、视网膜病变或心血管疾病等使人衰弱的并发症。胰岛移植因此作为糖尿病的最终治愈方法具有巨大潜力。然而,用于移植的胰岛供体来源短缺在很大程度上阻碍了这种治疗方法。在这方面,使用替代胰岛来源,如功能性内分泌细胞的体外培养、扩增和分化来治疗糖尿病,一直是糖尿病研究的一个主要重点。由于缺乏用于鉴定这些细胞的细胞标志物,胰岛干/祖细胞的身份一直难以捉摸或至少存在争议。最近在胰腺器官发生研究以及体外胰岛祖细胞鉴定研究方面取得的成功,为在体内和体外前瞻性地分离和表征这些细胞所必需的细胞标志物提供了巨大的见解。如果我们能够鉴定出有助于分离和纯化胰岛祖细胞的标志物,或确定胰腺细胞命运的因子,我们或许就能在体外促使它们转化为特定的内分泌细胞或胰腺。本文将聚焦于这个主题,并回顾胰岛祖细胞细胞标志物研究的最新成果。