Tissue-Engineered Microvasculature to Reperfuse Isolated Renal Glomeruli.
Tissue-Engineered Microvasculature to Reperfuse Isolated Renal Glomeruli.
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组织工程微血管再灌注离体肾小球。
DOI：
10.1089/ten.tea.2015.0060
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发表时间：
2015
影响因子：
--
通讯作者：
Pober,JordanS
中科院分区：
文献类型：
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作者：
Chang,WilliamGee;Fornoni,Alessia;Tietjen,Gregory;Mendez,JulioJ;Niklason,LauraE;Saltzman,WMark;Pober,JordanS
肾移植通常是终末期肾病最有效的治疗方法，但没有足够的供体器官来满足不断增长的需求。肾脏的组织工程是解决这一器官短缺的潜在方案。实现微血管灌注一直是工程组织超越薄肌肉化片如膀胱壁的主要障碍。我们的实验室以前曾报道，人脐静脉内皮细胞（ECs）转导抗凋亡蛋白Bcl-2将自发组织成灌注的微血管内的I型胶原凝胶植入免疫缺陷小鼠。为了测试该系统是否可用于灌注更复杂的结构，我们将Bcl-2转导的EC（Bcl-2-EC）与肾小球（肾脏的专门血管过滤单位）组合。将悬浮在I型胶原凝胶中的表达绿色荧光蛋白的大鼠肾小球显微切割后植入免疫缺陷小鼠体内，加入或不加入Bcl-2-EC。Bcl-2-ECs共植入可提高大鼠肾小球的存活率。活体罗丹明葡聚糖注射表明，存活的肾小球通过Bcl-2-EC衍生的微血管灌注。灌流的肾小球维持podocin染色，但透射电子显微镜显示内皮肿胀和足细胞足突消失。来自Bcl-2-EC的微血管与肾小球毛细血管的吻合提供了自组装微血管可以灌注专门的器官结构如肾小球的概念的证据，但是单独的灌注可能不足以维持正常的结构。
Kidney transplantation is often the most effective therapy for end-stage renal disease, but there are not enough donor organs to meet the rising demand. Tissue engineering of kidneys is a potential solution to this organ shortage. Achieving microvascular perfusion has been a major barrier to engineering tissues beyond thin muscularized sheets such as the bladder wall. Our laboratory has previously reported that human umbilical vein endothelial cells (ECs) transduced with the antiapoptotic protein Bcl-2 will spontaneously organize into perfused microvessels within type I collagen gels when implanted in immunodeficient mice. To test if this system can be used to perfuse more complex structures, we combined Bcl-2-transduced ECs (Bcl-2-ECs) with renal glomeruli, the specialized vascular filtration units of the kidney. Microdissected green fluorescent protein-expressing rat glomeruli suspended in type I collagen gels were implanted within immunodeficient mice with or without the inclusion of Bcl-2-ECs. Survival of rat glomeruli was enhanced by coimplantation with Bcl-2-ECs. Intravital rhodamine dextran injections demonstrated that surviving glomeruli were perfused through Bcl-2-EC-derived microvessels. Perfused glomeruli maintained podocin staining, but transmission electron microscopy revealed endothelial swelling and podocyte foot process effacement. Anastomosis of microvessels derived from Bcl-2-ECs with glomerular capillaries provides proof of concept that self-assembled microvessels can perfuse specialized organ structures such as glomeruli, but that perfusion alone may be insufficient to maintain normal structure.