Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853, USA.
Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853, USA.
Acta Biomater. 2019 Sep 1;95:131-151. doi: 10.1016/j.actbio.2019.05.051. Epub 2019 May 23.
The microvasculature in the pancreatic islet is highly specialized for glucose sensing and insulin secretion. Although pancreatic islet transplantation is a potentially life-changing treatment for patients with insulin-dependent diabetes, a lack of blood perfusion reduces viability and function of newly transplanted tissues. Functional vasculature around an implant is not only necessary for the supply of oxygen and nutrients but also required for rapid insulin release kinetics and removal of metabolic waste. Inadequate vascularization is particularly a challenge in islet encapsulation. Selectively permeable membranes increase the barrier to diffusion and often elicit a foreign body reaction including a fibrotic capsule that is not well vascularized. Therefore, approaches that aid in the rapid formation of a mature and robust vasculature in close proximity to the transplanted cells are crucial for successful islet transplantation or other cellular therapies. In this paper, we review various strategies to engineer vasculature for islet transplantation. We consider properties of materials (both synthetic and naturally derived), prevascularization, local release of proangiogenic factors, and co-transplantation of vascular cells that have all been harnessed to increase vasculature. We then discuss the various other challenges in engineering mature, long-term functional and clinically viable vasculature as well as some emerging technologies developed to address them. The benefits of physiological glucose control for patients and the healthcare system demand vigorous pursuit of solutions to cell transplant challenges. STATEMENT OF SIGNIFICANCE: Insulin-dependent diabetes affects more than 1.25 million people in the United States alone. Pancreatic islets secrete insulin and other endocrine hormones that control glucose to normal levels. During preparation for transplantation, the specialized islet blood vessel supply is lost. Furthermore, in the case of cell encapsulation, cells are protected within a device, further limiting delivery of nutrients and absorption of hormones. To overcome these issues, this review considers methods to rapidly vascularize sites and implants through material properties, pre-vascularization, delivery of growth factors, or co-transplantation of vessel supporting cells. Other challenges and emerging technologies are also discussed. Proper vascular growth is a significant component of successful islet transplantation, a treatment that can provide life-changing benefits to patients.
胰岛中的微血管对于葡萄糖感应和胰岛素分泌具有高度特异性。虽然胰岛移植是治疗胰岛素依赖型糖尿病患者的一种潜在改变生活的治疗方法，但缺乏血液灌注会降低新移植组织的活力和功能。植入物周围的功能性脉管系统不仅对于氧气和营养物质的供应是必要的，而且对于快速胰岛素释放动力学和代谢废物的清除也是必需的。血管生成不足在胰岛包封中尤其具有挑战性。选择性渗透膜增加了扩散的障碍，并且经常引起异物反应，包括血管化不良的纤维囊。因此，促进在接近移植细胞的位置快速形成成熟且强健的脉管系统的方法对于成功的胰岛移植或其他细胞疗法至关重要。在本文中，我们综述了用于胰岛移植的脉管工程的各种策略。我们考虑了材料（合成和天然衍生的）的特性、预先血管化、促血管生成因子的局部释放以及血管细胞的共移植，这些方法都被用于增加脉管系统。然后，我们讨论了在构建成熟、长期功能和临床可行的脉管系统方面的各种其他挑战，以及为解决这些问题而开发的一些新兴技术。为了患者和医疗保健系统的利益，需要积极寻求解决细胞移植挑战的方法。
胰岛素依赖型糖尿病仅在美国就影响了超过 125 万人。胰岛分泌胰岛素和其他内分泌激素，将葡萄糖控制在正常水平。在移植准备过程中，特殊的胰岛血管供应会丧失。此外，在细胞包封的情况下，细胞被保护在设备内，进一步限制了营养物质的输送和激素的吸收。为了克服这些问题，本综述考虑了通过材料特性、预先血管化、生长因子的递送或血管支持细胞的共移植来快速血管化部位和植入物的方法。还讨论了其他挑战和新兴技术。适当的血管生成是胰岛移植成功的重要组成部分，这种治疗方法可以为患者带来改变生活的益处。
