Carpenter Ryan, Oh Hye Jeong, Ham In-Hye, Kim Daeyoung, Hur Hoon, Lee Jungwoo
Department of Surgery, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon-si 16499, Gyeonggi-do, Republic of Korea.
Department of Mathematics & Statistics, University of Massachusetts, Amherst, Lederle Graduate Research Tower, 710 North Pleasant Street, Amherst, Massachusetts 01003, United States.
ACS Biomater Sci Eng. 2019 Dec 9;5(12):6667-6678. doi: 10.1021/acsbiomaterials.9b00978. Epub 2019 Nov 13.
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.
将人体组织异种移植到免疫缺陷小鼠体内已成为一种非常有价值的临床前模型，用于研究人类生物学和疾病进展，并预测临床反应。由于手术操作简单，且便于进行大体监测和先进的成像方式，皮下袋是组织移植最常见的解剖部位。然而，皮下植入的组织最初会经历氧气和营养供应的急剧变化以及机械变形的增加。在组织与宿主血管系统整合的这个急性期，会发生大量细胞死亡和组织纤维化，从而限制植入效率。此前，我们证明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，而无典型的异物包囊。在本研究中，我们研究了利用这种独特的宿主反应来改善组织异位移植到皮下部位的情况。与天然组织相比，支架辅助的组织保留了形态特征和血管密度，而无支架的组织则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物反应，以减少Ly6G细胞在移植组织内的定位。将患者来源的胃癌与支架共同移植，其植入水平与传统方法相当；然而，详细的免疫组织学特征显示，在研究结束时，增殖细胞（Ki67）和人类免疫细胞（CD45）的保留情况明显更好。我们设想，利用生物材料界面的免疫调节特性可能是一种有吸引力的策略，可改善异种移植的功能植入，并加速个性化诊断和新型治疗策略的开发。
