Developing Humanized Animal Models with Transplantable Human iPSC-Derived Cells
Establishing reliable and reproducible animal models for disease modelling, drug screening and the understanding of disease susceptibility and pathogenesis is critical. However, traditional animal models differ significantly from humans in terms of physiology, immune response, and pathogenesis. As a...
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IMR Press
2024-01-01
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Series: | Frontiers in Bioscience-Landmark |
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Online Access: | https://www.imrpress.com/journal/FBL/29/1/10.31083/j.fbl2901034 |
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author | Min Ma Jian-Yun Ge Yun-Zhong Nie Yu-Mei Li Yun-Wen Zheng |
author_facet | Min Ma Jian-Yun Ge Yun-Zhong Nie Yu-Mei Li Yun-Wen Zheng |
author_sort | Min Ma |
collection | DOAJ |
description | Establishing reliable and reproducible animal models for disease modelling, drug screening and the understanding of disease susceptibility and pathogenesis is critical. However, traditional animal models differ significantly from humans in terms of physiology, immune response, and pathogenesis. As a result, it is difficult to translate laboratory findings into biomedical applications. Although several animal models with human chimeric genes, organs or systems have been developed in the past, their limited engraftment rate and physiological functions are a major obstacle to realize convincing models of humans. The lack of human transplantation resources and insufficient immune tolerance of recipient animals are the main challenges that need to be overcome to generate fully humanized animals. Recent advances in gene editing and pluripotent stem cell-based xenotransplantation technologies offer opportunities to create more accessible human-like models for biomedical research. In this article, we have combined our laboratory expertise to summarize humanized animal models, with a focus on hematopoietic/immune system and liver. We discuss their generation strategies and the potential donor cell sources, with particular attention given to human pluripotent stem cells. In particular, we discuss the advantages, limitations and emerging trends in their clinical and pharmaceutical applications. By providing insights into the current state of humanized animal models and their potential for biomedical applications, this article aims to advance the development of more accurate and reliable animal models for disease modeling and drug screening. |
first_indexed | 2024-03-08T09:37:21Z |
format | Article |
id | doaj.art-f488d97e69c947f5b40a3b3a6bc76011 |
institution | Directory Open Access Journal |
issn | 2768-6701 |
language | English |
last_indexed | 2024-03-08T09:37:21Z |
publishDate | 2024-01-01 |
publisher | IMR Press |
record_format | Article |
series | Frontiers in Bioscience-Landmark |
spelling | doaj.art-f488d97e69c947f5b40a3b3a6bc760112024-01-30T07:44:35ZengIMR PressFrontiers in Bioscience-Landmark2768-67012024-01-012913410.31083/j.fbl2901034S2768-6701(23)01171-1Developing Humanized Animal Models with Transplantable Human iPSC-Derived CellsMin Ma0Jian-Yun Ge1Yun-Zhong Nie2Yu-Mei Li3Yun-Wen Zheng4Institute of Regenerative Medicine, and Department of Dermatology, Affiliated Hospital of Jiangsu University, Jiangsu University, 212001 Zhenjiang, Jiangsu, ChinaGuangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, and South China Institute of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, 529020 Jiangmen, Guangdong, ChinaCenter for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, The University of Tokyo, 108-8639 Tokyo, JapanInstitute of Regenerative Medicine, and Department of Dermatology, Affiliated Hospital of Jiangsu University, Jiangsu University, 212001 Zhenjiang, Jiangsu, ChinaInstitute of Regenerative Medicine, and Department of Dermatology, Affiliated Hospital of Jiangsu University, Jiangsu University, 212001 Zhenjiang, Jiangsu, ChinaEstablishing reliable and reproducible animal models for disease modelling, drug screening and the understanding of disease susceptibility and pathogenesis is critical. However, traditional animal models differ significantly from humans in terms of physiology, immune response, and pathogenesis. As a result, it is difficult to translate laboratory findings into biomedical applications. Although several animal models with human chimeric genes, organs or systems have been developed in the past, their limited engraftment rate and physiological functions are a major obstacle to realize convincing models of humans. The lack of human transplantation resources and insufficient immune tolerance of recipient animals are the main challenges that need to be overcome to generate fully humanized animals. Recent advances in gene editing and pluripotent stem cell-based xenotransplantation technologies offer opportunities to create more accessible human-like models for biomedical research. In this article, we have combined our laboratory expertise to summarize humanized animal models, with a focus on hematopoietic/immune system and liver. We discuss their generation strategies and the potential donor cell sources, with particular attention given to human pluripotent stem cells. In particular, we discuss the advantages, limitations and emerging trends in their clinical and pharmaceutical applications. By providing insights into the current state of humanized animal models and their potential for biomedical applications, this article aims to advance the development of more accurate and reliable animal models for disease modeling and drug screening.https://www.imrpress.com/journal/FBL/29/1/10.31083/j.fbl2901034humanized animalhuman pluripotent stem cellsimmunodeficient animalxenotransplantation |
spellingShingle | Min Ma Jian-Yun Ge Yun-Zhong Nie Yu-Mei Li Yun-Wen Zheng Developing Humanized Animal Models with Transplantable Human iPSC-Derived Cells Frontiers in Bioscience-Landmark humanized animal human pluripotent stem cells immunodeficient animal xenotransplantation |
title | Developing Humanized Animal Models with Transplantable Human iPSC-Derived Cells |
title_full | Developing Humanized Animal Models with Transplantable Human iPSC-Derived Cells |
title_fullStr | Developing Humanized Animal Models with Transplantable Human iPSC-Derived Cells |
title_full_unstemmed | Developing Humanized Animal Models with Transplantable Human iPSC-Derived Cells |
title_short | Developing Humanized Animal Models with Transplantable Human iPSC-Derived Cells |
title_sort | developing humanized animal models with transplantable human ipsc derived cells |
topic | humanized animal human pluripotent stem cells immunodeficient animal xenotransplantation |
url | https://www.imrpress.com/journal/FBL/29/1/10.31083/j.fbl2901034 |
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