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在毛里求斯食蟹猴主要组织相容性复合体定义的移植模型中,主要组织相容性复合体匹配的动脉与自体动脉具有相似的通畅率。

Major Histocompatibility Complex-Matched Arteries Have Similar Patency to Autologous Arteries in a Mauritian Cynomolgus Macaque Major Histocompatibility Complex-Defined Transplant Model.

机构信息

Department of Regenerative Biology Morgridge Institute for Research Madison WI.

Wisconsin National Primate Research Center University of Wisconsin-Madison WI.

出版信息

J Am Heart Assoc. 2019 Aug 6;8(15):e012135. doi: 10.1161/JAHA.119.012135. Epub 2019 Jul 17.

Abstract

Background Arterial bypass and interposition grafts are used routinely across multiple surgical subspecialties. Current options include both autologous and synthetic materials; however, each graft presents specific limitations. Engineering artificial small-diameter arteries with vascular cells derived from induced pluripotent stem cells could provide a useful therapeutic solution. Banking induced pluripotent stem cells from rare individuals who are homozygous for human leukocyte antigen alleles has been proposed as a strategy to facilitate economy of scale while reducing the potential for rejection of induced pluripotent stem cell-derived transplanted tissues. Currently, there is no standardized model to study transplantation of small-diameter arteries in major histocompatibility complex-defined backgrounds. Methods and Results In this study, we developed a limb-sparing nonhuman primate model to study arterial allotransplantation in the absence of immunosuppression. Our model was used to compare degrees of major histocompatibility complex matching between arterial grafts and recipient animals with long-term maintenance of patency and function. Unexpectedly, we (1) found that major histocompatibility complex partial haplomatched allografts perform as well as autologous control grafts; (2) detected little long-term immune response in even completely major histocompatibility complex mismatched allografts; and (3) observed that arterial grafts become almost completely replaced over time with recipient cells. Conclusions Given these findings, induced pluripotent stem cell-derived tissue-engineered blood vessels may prove to be promising and customizable grafts for future use by cardiac, vascular, and plastic surgeons.

摘要

背景 动脉旁路和间置移植物在多个外科亚专业中常规使用。目前的选择包括自体和合成材料;然而,每种移植物都有特定的局限性。使用源自诱导多能干细胞的血管细胞来工程人工小直径动脉,可以提供一种有用的治疗解决方案。从纯合人白细胞抗原等位基因的罕见个体中储存诱导多能干细胞,被提议作为一种策略,以促进规模经济,同时减少诱导多能干细胞衍生的移植组织排斥的可能性。目前,还没有标准化的模型来研究主要组织相容性复合体定义背景下的小直径动脉移植。 方法和结果 在这项研究中,我们开发了一种肢体保留的非人类灵长类动物模型,以在不使用免疫抑制的情况下研究动脉同种异体移植。我们的模型用于比较动脉移植物和受体动物之间主要组织相容性复合体匹配程度,以长期保持通畅和功能。出乎意料的是,我们发现(1)主要组织相容性复合体部分单倍型匹配的同种异体移植物的性能与自体对照移植物一样好;(2)在完全主要组织相容性复合体不匹配的同种异体移植物中,检测到很少的长期免疫反应;(3)观察到随着时间的推移,动脉移植物逐渐被受体细胞完全替代。 结论 鉴于这些发现,诱导多能干细胞衍生的组织工程血管可能被证明是有前途的、可定制的移植物,可用于未来的心脏、血管和整形外科医生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44e1/6761673/8eb17c4eb084/JAH3-8-e012135-g001.jpg

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