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Cell Rep. 2017 Aug 22;20(8):1978-1990. doi: 10.1016/j.celrep.2017.08.003.

Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics.

Author information

1
Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA; Department of Medicine, Stanford University School of Medicine, Stanford, California, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA; Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
2
Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA; Department of Medicine, Stanford University School of Medicine, Stanford, California, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA.
3
Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA; Department of Medicine, Stanford University School of Medicine, Stanford, California, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA; Department of Comparative Medicine, Stanford University School of Medicine, Stanford, California, USA.
4
Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
5
Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
6
Diabetes Center of Excellence, Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
7
Diabetes Center of Excellence, Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA. Electronic address: dale.greiner@umassmed.edu.
8
The Jackson Laboratory, Bar Harbor, ME, USA. Electronic address: lenny.shultz@jax.org.
9
Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, USA; Department of Medicine, Stanford University School of Medicine, Stanford, California, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, USA. Electronic address: joewu@stanford.edu.

Abstract

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.

KEYWORDS:

T cell exhaustion; allograft; humanized mice; immunogenicity; pluripotent stem cells; stem cell therapeutics; wasting disease

PMID:
28834758
PMCID:
PMC5573767
DOI:
10.1016/j.celrep.2017.08.003
[Indexed for MEDLINE]
Free PMC Article

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