Scaffold-Assisted Ectopic Transplantation of Internal Organs and Patient-Derived Tumors.
Scaffold-Assisted Ectopic Transplantation of Internal Organs and Patient-Derived Tumors.
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DOI：
10.1021/acsbiomaterials.9b00978
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发表时间：
2019-12-09
影响因子：
5.8
通讯作者：
Lee J
中科院分区：
文献类型：
--
作者：
Carpenter R;Oh HJ;Ham IH;Kim D;Hur H;Lee J
人体组织异种移植到免疫缺陷小鼠体内已经成为研究人类生物学和疾病进展以及预测临床反应的宝贵临床前模型。组织移植最常见的解剖部位是皮下袋，因为手术操作简单，便于大体监测和先进的成像方式。然而，皮下植入组织最初经历氧气和营养供应的急剧变化和增加的机械变形。在组织与宿主血管整合的急性阶段，大量细胞死亡和组织纤维化发生，限制了植入效率。先前，我们证明了倒置胶体晶体水凝胶支架的植入可触发促血管生成和免疫调节功能，而没有特征性的异物包裹。在这项研究中，我们研究了使用这种独特的宿主反应来改善组织异位移植到皮下部位。与天然组织相比，支架辅助组织保留了形态特征和血管密度，而无支架组织塌陷且血管化程度较低。值得注意的是，支撑生物材料支架调节了异体反应，减少了移植组织中Ly6G+细胞的定位。患者源性胃癌与支架的联合移植与传统方法的移植水平相当；然而，详细的免疫组织学表征显示，在研究结束时，增殖细胞（Ki67+）和人类免疫细胞（CD45+）的保留率显著提高。我们设想利用生物材料界面的免疫调节特性可以成为一种有吸引力的策略，以改善异种移植的功能植入，加速个体化诊断和新治疗策略的发展。
Xenotransplantation of human tissues into immunodeficient mice has emerged as an invaluable preclinical model to study human biology and disease progression and predict clinical response. The most common anatomical site for tissue transplantation is the subcutaneous pocket due to simple surgical procedures and accessibility for gross monitoring and advanced imaging modalities. However, subcutaneously implanted tissues initially experience a sharp change in oxygen and nutrient supply and increased mechanical deformation. During this acute phase of tissue integration to the host vasculature, substantial cell death and tissue fibrosis occur limiting engraftment efficiency. Previously, we demonstrated that the implantation of inverted colloidal crystal hydrogel scaffolds triggers proangiogenic and immunomodulatory functions without characteristic foreign body encapsulation. In this study, we examine the use of this unique host response to improve the ectopic transplantation of tissues to the subcutaneous site. Scaffold-assisted tissues preserved morphological features and blood vessel density compared to native tissues, whereas scaffold-free tissues collapsed and were less vascularized. Notably, the supporting biomaterial scaffold modulated the foreign body response to reduce the localization of Ly6G+ cells within the transplanted tissues. Cotransplantation of patient-derived gastric cancer with a scaffold resulted in a comparable level of engraftment to conventional methods; however, detailed immunohistological characterization revealed significantly better retention of proliferative cells (Ki67+) and human immune cells (CD45+) by the end of the study. We envision that leveraging the immunomodulatory properties of biomaterial interfaces can be an attractive strategy to improve the functional engraftment of xenotransplants and accelerate individualized diagnostics and the development of novel therapeutic strategies.
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影响因子：
14
作者：
Chen, Sulin;Jones, Jacqueline A.;Xu, Yongan;Low, Hong-Yee;Anderson, James M.;Leong, Kam W.
通讯作者：
Leong, Kam W.
影响因子：
20.3
作者：
Christoffersson, Gustaf;Vagesjo, Evelina;Phillipson, Mia
通讯作者：
Phillipson, Mia
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
28.1
作者：
Carpenter, Ryan A.;Kwak, Jun-Goo;Lee, Jungwoo
通讯作者：
Lee, Jungwoo
影响因子：
30.8
作者：
Ben-David U;Ha G;Tseng YY;Greenwald NF;Oh C;Shih J;McFarland JM;Wong B;Boehm JS;Beroukhim R;Golub TR
通讯作者：
Golub TR