Immune Response of Transplanted Kidney Tissues Assembled from Organoid Building Blocks

• DOI: 10.1101/2023.08.26.551822
• Publication Date: 2023-08-28T10:16:19Z
• Authors: Thiago J. Borges; Yoshikazu Ganchiku; Jeffrey O. Aceves; Ronald van Gaal; Sebastien G. M. Uzel; Jonathan E. Rubins; Kenichi Kobayashi; Ken Hiratsuka; Murat Tekguc; Ivy A. Rosales; Guilherme T. Ribas; Karina Lima; Rodrigo B. Gassen; Ryuji Morizane; Jennifer A. Lewis; Leonardo V. Riella
• Keywords: Organoid

Summary The increasing scarcity of organs and the significant morbidity linked to dialysis requires development engineered kidney tissues from human-induced pluripotent stem cells. To accomplish this, integrative approaches that synergize scalable organoid differentiation, tissue biomanufacturing, comprehensive assessment their immune response host integration are essential. Here, we create human composed building blocks (OBBs) transplant them into mice reconstituted with allogeneic We assess vascular integration, in vivo maturation, ability trigger responses. Tissue-infiltrating cells effector T innate This infiltration leads injury characterized by reduced microvasculature, enhanced cell apoptosis, a unique inflammatory gene signature comparable organ rejection humans. Upon treatment immunosuppressive agent Rapamycin, induced is greatly suppressed. Our model serves as translational platform study immunogenicity develop novel therapeutic targets for rejection.