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...

Full description

Bibliographic Details
Main Authors: Min Ma, Jian-Yun Ge, Yun-Zhong Nie, Yu-Mei Li, Yun-Wen Zheng
Format: Article
Language:English
Published: IMR Press 2024-01-01
Series:Frontiers in Bioscience-Landmark
Subjects:
Online Access:https://www.imrpress.com/journal/FBL/29/1/10.31083/j.fbl2901034
_version_ 1797338851732094976
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
work_keys_str_mv AT minma developinghumanizedanimalmodelswithtransplantablehumanipscderivedcells
AT jianyunge developinghumanizedanimalmodelswithtransplantablehumanipscderivedcells
AT yunzhongnie developinghumanizedanimalmodelswithtransplantablehumanipscderivedcells
AT yumeili developinghumanizedanimalmodelswithtransplantablehumanipscderivedcells
AT yunwenzheng developinghumanizedanimalmodelswithtransplantablehumanipscderivedcells