Brown David L, Meagher Peter J, Knight Kenneth R, Keramidaris Effie, Romeo-Meeuw Rosalind, Penington Anthony J, Morrison Wayne A
Bernard O'Brien Institute of Microsurgery and the Department of Surgery, University of Melbourne, St. Vincent's Hospital, Melbourne, Australia.
Cell Transplant. 2006;15(4):319-24.
As in vivo tissue engineering of complex tissues and organs progresses, there is a need for an independently vascularized, alterable, and recoverable model. Current models of islet cell transplantation (release into the portal venous system, placement under the renal capsule, and microencapsulation) lack these qualities. We have developed a model of angiogenesis and spontaneous tissue generation in the rat that lends itself as a potential platform for tissue engineering. In this experiment, we examined the effectiveness of such a model in addressing some of the shortcomings of endocrine pancreatic transplantation. An arteriovenous loop was created in the groins of five adult inbred Sprague-Dawley rats, and placed within polycarbonate chambers. Isolated pancreatic islet cell clusters were placed within the chambers, suspended in a matrix of Matrigel. The chambers were recovered at 3 weeks, and the newly generated tissue was processed for histologic and immunohistochemical analysis. By 3 weeks, spontaneous generation of angiogenesis and collagen matrix and deposition of a collagen matrix was observed. Surviving islet cells were identified by histology and their viability was confirmed via immunohistochemistry for insulin and glucagon. This study demonstrates the ability to maintain viability and functionality of transplanted islet cells on a tissue-engineered platform with an independent vascular supply. The model provides the ability to alter the graft environment via matrix substitution, cellular coculture, and administration of growth factors. The transplanted tissues are recoverable without animal sacrifice and are microsurgically transferable. This model may provide an in vivo culture platform for the study of islet transplantation.
随着复杂组织和器官的体内组织工程不断发展,需要一种具有独立血管化、可改变且可恢复的模型。目前的胰岛细胞移植模型(释放到门静脉系统、置于肾被膜下以及微囊化)缺乏这些特性。我们已经开发出一种大鼠血管生成和自发组织生成模型,它有望成为组织工程的潜在平台。在本实验中,我们检验了该模型在解决内分泌胰腺移植某些缺点方面的有效性。在五只成年近交系斯普拉格 - 道利大鼠的腹股沟区构建动静脉环,并将其置于聚碳酸酯小室中。将分离的胰岛细胞团置于小室内,悬浮于基质胶基质中。3周后回收小室,对新生成的组织进行组织学和免疫组织化学分析。到3周时,观察到血管生成和胶原基质的自发形成以及胶原基质的沉积。通过组织学鉴定存活的胰岛细胞,并通过胰岛素和胰高血糖素的免疫组织化学确认其活力。本研究证明了在具有独立血管供应的组织工程平台上维持移植胰岛细胞活力和功能的能力。该模型能够通过基质替代、细胞共培养和生长因子给药来改变移植环境。移植组织可在不牺牲动物的情况下回收,并且可通过显微手术进行转移。该模型可能为胰岛移植研究提供一个体内培养平台。