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Scaffold-Assisted Ectopic Transplantation of Internal Organs and Patient-Derived Tumors

Authors
Carpenter, R; Oh, HJ; Ham, IH; Kim, D; Hur, H; Lee, J
Citation
ACS biomaterials science & engineering, 5(12). : 6667-6678, 2019
Journal Title
ACS biomaterials science & engineering
ISSN
2373-9878
Abstract
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.
Keywords
tissue transplantationbiomaterialimmune modulationpatient-derived xenografttissue engineeringgastric cancer
DOI
10.1021/acsbiomaterials.9b00978
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Surgery
AJOU Authors
함, 인혜허, 훈
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