Gunawardana Subhadra C, Benninger Richard K P, Piston David W
Dept. of Molecular Physiology and Biophysics, Vanderbilt Univ. School of Medicine, Nashville, TN 37232, USA.
Am J Physiol Endocrinol Metab. 2009 Feb;296(2):E323-32. doi: 10.1152/ajpendo.90544.2008. Epub 2008 Dec 9.
Islet transplantation is a promising therapeutic approach for type 1 diabetes. However, current success rates are low due to progressive graft failure in the long term and inability to monitor graft development in vivo. Other limitations include the necessity of initial invasive surgery and continued immunosuppressive therapy. We report an alternative transplantation strategy with the potential to overcome these problems. This technique involves transplantation of embryonic pancreatic tissue into recipients' subcutaneous space, eliminating the need for invasive surgery and associated risks. Current results in mouse models of type 1 diabetes show that embryonic pancreatic transplants in the subcutaneous space can normalize blood glucose homeostasis and achieve extensive endocrine differentiation and vascularization. Furthermore, modern imaging techniques such as two-photon excitation microscopy (TPEM) can be employed to monitor transplants through the intact skin in a completely noninvasive manner. Thus, this strategy is a convenient alternative to islet transplantation in diabetic mice and has the potential to be translated to human clinical applications with appropriate modifications.
胰岛移植是治疗1型糖尿病的一种有前景的治疗方法。然而,由于长期移植失败以及无法在体内监测移植的发展,目前的成功率较低。其他局限性包括初始侵入性手术的必要性和持续的免疫抑制治疗。我们报告了一种有可能克服这些问题的替代移植策略。该技术涉及将胚胎胰腺组织移植到受体的皮下空间,从而消除了侵入性手术和相关风险。目前在1型糖尿病小鼠模型中的结果表明,皮下空间的胚胎胰腺移植可以使血糖稳态正常化,并实现广泛的内分泌分化和血管化。此外,诸如双光子激发显微镜(TPEM)等现代成像技术可以以完全非侵入性的方式通过完整皮肤监测移植情况。因此,该策略是糖尿病小鼠胰岛移植的一种便捷替代方法,并且有可能经过适当修改后转化为人类临床应用。