Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics

Nigel G. Kooreman; Patricia E. de Almeida; Jonathan P. Stack; Raman V. Nelakanti; Sebastian Diecke; Ning-Yi Shao; Rutger-Jan Swijnenburg; Veronica Sanchez-Freire; Elena Matsa; Chun Liu; Andrew J. Connolly; Jaap F. Hamming; Paul H.A. Quax; Michael A. Brehm; Dale L. Greiner; Leonard D. Shultz; Joseph C. Wu

doi:10.1016/j.celrep.2017.08.003

Cell Reports (Aug 2017)

Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics

Nigel G. Kooreman,
Patricia E. de Almeida,
Jonathan P. Stack,
Raman V. Nelakanti,
Sebastian Diecke,
Ning-Yi Shao,
Rutger-Jan Swijnenburg,
Veronica Sanchez-Freire,
Elena Matsa,
Chun Liu,
Andrew J. Connolly,
Jaap F. Hamming,
Paul H.A. Quax,
Michael A. Brehm,
Dale L. Greiner,
Leonard D. Shultz,
Joseph C. Wu

Affiliations

Nigel G. Kooreman: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA
Patricia E. de Almeida: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA
Jonathan P. Stack: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA
Raman V. Nelakanti: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA
Sebastian Diecke: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA
Ning-Yi Shao: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA
Rutger-Jan Swijnenburg: Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
Veronica Sanchez-Freire: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA
Elena Matsa: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA
Chun Liu: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA
Andrew J. Connolly: Department of Pathology, Stanford University School of Medicine, Stanford, California, USA
Jaap F. Hamming: Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
Paul H.A. Quax: Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
Michael A. Brehm: Diabetes Center of Excellence, Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA
Dale L. Greiner: Diabetes Center of Excellence, Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA
Leonard D. Shultz: The Jackson Laboratory, Bar Harbor, ME, USA
Joseph C. Wu: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA

DOI: https://doi.org/10.1016/j.celrep.2017.08.003
Journal volume & issue: Vol. 20, no. 8
pp. 1978 – 1990

Abstract

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There is growing interest in using embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) derivatives for tissue regeneration. However, an increased understanding of human immune responses to stem cell-derived allografts is necessary for maintaining long-term graft persistence. To model this alloimmunity, humanized mice engrafted with human hematopoietic and immune cells could prove to be useful. In this study, an in-depth analysis of graft-infiltrating human lymphocytes and splenocytes revealed that humanized mice incompletely model human immune responses toward allogeneic stem cells and their derivatives. Furthermore, using an “allogenized” mouse model, we show the feasibility of reconstituting immunodeficient mice with a functional mouse immune system and describe a key role of innate immune cells in the rejection of mouse stem cell allografts.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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