Exploring immune response toward transplanted human kidney tissues assembled from organoid building blocks

Thiago J. Borges; Yoshikazu Ganchiku; Jeffrey O. Aceves; Ronald van Gaal; Sebastien G.M. Uzel; Ivy A. Rosales; Jonathan E. Rubins; Kenichi Kobayashi; Ken Hiratsuka; Murat Tekguc; Guilherme T. Ribas; Karina Lima; Rodrigo B. Gassen; Ryuji Morizane; Jennifer A. Lewis; Leonardo V. Riella

iScience (Oct 2024)

Exploring immune response toward transplanted human kidney tissues assembled from organoid building blocks

Thiago J. Borges,
Yoshikazu Ganchiku,
Jeffrey O. Aceves,
Ronald van Gaal,
Sebastien G.M. Uzel,
Ivy A. Rosales,
Jonathan E. Rubins,
Kenichi Kobayashi,
Ken Hiratsuka,
Murat Tekguc,
Guilherme T. Ribas,
Karina Lima,
Rodrigo B. Gassen,
Ryuji Morizane,
Jennifer A. Lewis,
Leonardo V. Riella

Affiliations

Thiago J. Borges: Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United states
Yoshikazu Ganchiku: Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United states
Jeffrey O. Aceves: Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, United states
Ronald van Gaal: Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, United states
Sebastien G.M. Uzel: Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, United states; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United states
Ivy A. Rosales: Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United states; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United states
Jonathan E. Rubins: Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, United states
Kenichi Kobayashi: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United states; Nephrology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United states
Ken Hiratsuka: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United states; Nephrology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United states
Murat Tekguc: Nephrology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United states; Harvard Stem Cell Institute (HSCI), Cambridge, MA, United states
Guilherme T. Ribas: Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United states
Karina Lima: Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United states
Rodrigo B. Gassen: Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United states
Ryuji Morizane: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United states; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United states; Nephrology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United states
Jennifer A. Lewis: Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, United states; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, United states; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United states
Leonardo V. Riella: Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United states; Corresponding author

Journal volume & issue: Vol. 27, no. 10
p. 110957

Abstract

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

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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