Alloimmune Responses of Humanized Mice to Human Pluripotent Stem Cell Therapeutics
| Autor: | Veronica Sanchez-Freire, Rutger-Jan Swijnenburg, Sebastian Diecke, Jaap F. Hamming, Chun Liu, Patrícia de Almeida, Raman Nelakanti, Dale L. Greiner, Andrew J. Connolly, Michael A. Brehm, Elena Matsa, Jonathan P. Stack, Joseph C. Wu, Nigel G. Kooreman, Leonard D. Shultz, Paul H.A. Quax, Ning-Yi Shao |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
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Graft Rejection 0301 basic medicine allograft Transplantation Conditioning chemical and pharmacologic phenomena immunogenicity Biology General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences 0302 clinical medicine Immune system Cancer stem cell stem cell therapeutics Animals Humans Induced pluripotent stem cell lcsh:QH301-705.5 T cell exhaustion Induced stem cells Innate immune system Alloimmunity Hematopoietic Stem Cell Transplantation Embryonic stem cell Immunity Innate 3. Good health Cell biology Disease Models Animal humanized mice 030104 developmental biology lcsh:Biology (General) 030220 oncology & carcinogenesis wasting disease Immunology pluripotent stem cells Technology Platforms Stem cell |
| Zdroj: | Cell Reports, 20(8), 1978-1990 Cell Reports Cell Reports, Vol 20, Iss 8, Pp 1978-1990 (2017) |
| Popis: | Summary 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. Graphical Abstract Highlights • Innate immunity is crucial in rejection of minor HA mismatched grafts • Stem cell alloimmune responses modeled with an “allogenized mouse” • Humanized mice are unable to fully model immune responses to stem cell allografts • Splenocytes and graft-infiltrating lymphocytes display an exhausted phenotype Kooreman et al. use various types of humanized mice for the modeling of pluripotent stem cell alloimmunity. They report the development of a wasting disease-like syndrome within these mice over time, limiting their functionality, and provide ways to address this by using an immune reconstituted “allogenized” mouse model. |
| Databáze: | OpenAIRE |
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