Pileggi Antonello, Molano R Damaris, Ricordi Camillo, Zahr Elsie, Collins Jill, Valdes Rafael, Inverardi Luca
Diabetes Research Institute, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA, and Hospital Infantil de México Federico Gómez, Departamento de Cirugía y Trasplantes, Facultad de Medicina UNAM, México DF, México.
Transplantation. 2006 May 15;81(9):1318-24. doi: 10.1097/01.tp.0000203858.41105.88.
Transplantation of pancreatic islets for the treatment of type 1 diabetes allows for physiologic glycemic control and insulin-independence when sufficient islets are implanted via the portal vein into the liver. Intrahepatic islet implantation requires specific infrastructure and expertise, and risks inherent to the procedure include bleeding, thrombosis, and elevation of portal pressure. Additionally, the relatively higher drug metabolite concentrations in the liver may contribute to the delayed loss of graft function of recent clinical trials. Identification of alternative implantation sites using biocompatible devices may be of assistance improving graft outcome. A desirable bioartificial pancreas should be easy to implant, biopsy, and retrieve, while allowing for sustained graft function. The subcutaneous (SC) site may require a minimally invasive procedure performed under local anesthesia, but its use has been hampered so far by lack of early vascularization, induction of local inflammation, and mechanical stress on the graft.
Chemically diabetic rats received syngeneic islets into the liver or SC into a novel biocompatible device consisting of a cylindrical stainless-steel mesh. The device was implanted 40 days prior to islet transplantation to allow embedding by connective tissue and neovascularization. Reversal of diabetes and glycemic control was monitored after islet transplantation.
Syngeneic islets transplanted into a SC, neovascularized device restored euglycemia and sustained function long-term. Removal of graft-bearing devices resulted in hyperglycemia. Explanted grafts showed preserved islets and intense vascular networks.
Ease of implantation, biocompatibility, and ability to maintain long-term graft function support the potential of our implantable device for cellular-based reparative therapies.
对于1型糖尿病的治疗而言，当通过门静脉将足够数量的胰岛植入肝脏时，胰岛移植可实现生理性血糖控制并使患者不再依赖胰岛素。肝内胰岛植入需要特定的基础设施和专业技术，该手术固有的风险包括出血、血栓形成以及门静脉压力升高。此外，肝脏中相对较高的药物代谢物浓度可能导致近期临床试验中移植功能延迟丧失。使用生物相容性装置确定替代植入部位可能有助于改善移植结果。理想的生物人工胰腺应易于植入、活检和取出，同时具备持续的移植功能。皮下（SC）部位可能需要在局部麻醉下进行微创手术，但其应用目前因缺乏早期血管化、局部炎症诱导以及移植体受到机械应力而受到阻碍。
化学诱导糖尿病大鼠接受同基因胰岛移植到肝脏中，或通过皮下植入到一种新型生物相容性装置中，该装置由圆柱形不锈钢网组成。该装置在胰岛移植前40天植入，以使结缔组织能够包埋并实现新血管形成。胰岛移植后监测糖尿病的逆转和血糖控制情况。
移植到皮下且已形成新血管的装置中的同基因胰岛恢复了正常血糖水平，并长期维持功能。移除带有移植体的装置会导致血糖升高。取出的移植体显示胰岛保存完好且血管网络密集。
易于植入、生物相容性以及维持长期移植功能的能力，支持了我们的可植入装置在基于细胞的修复治疗中的潜力。
