Suen Po Man, Li Karen, Chan Juliana C N, Leung Po Sing
Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin.
Int J Biochem Cell Biol. 2006;38(5-6):951-60. doi: 10.1016/j.biocel.2005.08.005. Epub 2005 Sep 7.
Fetal pancreatic tissue has been suggested as a possible cell source for islet replacement therapy in type 1 diabetes mellitus. This tissue consists of a small amount of beta-cells, but a raft of immature and/or progenitor cells which nonetheless have the potential to proliferate and differentiate into functional insulin-producing cells. Freshly isolated fetal islet-like cell clusters are poorly responsive to glucose challenge, compared with adult islets. Upon exposure to appropriate growth factors and microenvironments, both the expansion and differentiation of fetal islet-like cell clusters can be enhanced. In this study, we investigated the role of exendin-4, a long-acting analogue of glucagon-like peptide 1 in the promotion of functional maturation of transplanted fetal islet-like cell clusters in vivo. Both blood glucose levels and body weights of transplanted diabetic mice treated with exendin-4 improved significantly compared with the transplanted group not subjected to exendin-4 treatment during the 3-month post-transplantation period. In addition, blood glucose levels on formal glucose challenge were also significantly improved by the end of the experiments. In the exendin-4-treated group, there were revascularization and insulin-producing cells as evidenced by positive immunostaining of the Lectins Bandeiraea simplicifolia and insulin, respectively, in the graft bearing kidney. These data indicate that in vivo exendin-4 treatment may enhance the growth and differentiation of fetal mice islet-like cell clusters, thus promoting the functional maturation of the graft after transplantation.
胎儿胰腺组织被认为是1型糖尿病胰岛替代治疗的一种可能的细胞来源。这种组织由少量的β细胞以及大量未成熟和/或祖细胞组成，这些细胞仍有增殖并分化为功能性胰岛素产生细胞的潜力。与成年胰岛相比，新鲜分离的胎儿胰岛样细胞簇对葡萄糖刺激反应较差。在暴露于适当的生长因子和微环境时，胎儿胰岛样细胞簇的扩增和分化均可得到增强。在本研究中，我们调查了艾塞那肽-4（胰高血糖素样肽1的长效类似物）在促进体内移植的胎儿胰岛样细胞簇功能成熟中的作用。在移植后3个月期间，与未接受艾塞那肽-4治疗的移植组相比，接受艾塞那肽-4治疗的移植糖尿病小鼠的血糖水平和体重均显著改善。此外，在实验结束时，正式葡萄糖刺激后的血糖水平也显著改善。在艾塞那肽-4治疗组中，移植肾脏的移植物中分别通过单叶豆凝集素和胰岛素的阳性免疫染色证明有血管再生和胰岛素产生细胞。这些数据表明，体内艾塞那肽-4治疗可能增强胎儿小鼠胰岛样细胞簇的生长和分化，从而促进移植后移植物的功能成熟。
