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Humanized immune system animal models and their recent applications
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Nicolas Skuli1, Rudra B. Amin1, A'ishah Bakayoko2, Marisa Kruidenier2, Sahara Aqui2, Sarah J. Skuli3, Terence P. Gade1
Animal Models and Experimental Medicine | 2026, 9(7) : 1310 - 1324
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Animal Models and Experimental Medicine | 2026, 9(7): 1310-1324
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Humanized immune system animal models and their recent applications
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Nicolas Skuli1, Rudra B. Amin1, A'ishah Bakayoko2, Marisa Kruidenier2, Sahara Aqui2, Sarah J. Skuli3, Terence P. Gade1
Affiliations
  • 1PIGI Lab, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  • 2Stem Cell and Xenograft Core, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  • 3Skuli Lab, Division of Hematology/Oncology, University of Cincinnati, College of Medicine, Department of Medicine, Cincinnati, Ohio, USA
Published: 2026-07-28 doi: 10.1002/ame2.70212
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Human or humanized immune system (HIS) animal models have emerged as indispensable tools for studying human biology and disease in vivo. By engrafting human hematopoietic and hematopoietic stem cells (HSC) into immunodeficient hosts, these models have enabled the development of a functional HIS, allowing the study of immune responses, disease mechanisms, and therapeutic interventions in a physiologically relevant setting. HIS models have broad applications across cancer research, infectious disease, regenerative medicine, and immunotherapy development. This review provides a comprehensive overview of the current landscape of HIS model generation, including HSC-based approaches, host strain selection, and recent advances involving genetically engineered mouse models expressing human cytokines and human leukocyte antigen molecules. We evaluated the strengths and limitations of these models, including issues with incomplete immune reconstitution and species-specific incompatibilities. We also discuss their increasing role in preclinical drug development and explore emerging innovations such as multitissue humanization and genome-editing strategies. As HIS models continue to evolve, they provide strong opportunities to bridge basic research and clinical translation.

animal science  /  humanized mice  /  immunotherapy  /  patient-derived xenografts  /  vaccines
Nicolas Skuli, Rudra B. Amin, A'ishah Bakayoko, Marisa Kruidenier, Sahara Aqui, Sarah J. Skuli, Terence P. Gade. Humanized immune system animal models and their recent applications[J]. Animal Models and Experimental Medicine, 2026 , 9 (7) : 1310 -1324 . DOI: 10.1002/ame2.70212
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Article Info
doi: 10.1002/ame2.70212
  • Receive Date：2025-12-08
  • Online Date：2026-08-06
  • Published：2026-07-28
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History
  • Received：2025-12-08
  • Revised：2026-03-12
  • Accepted：2026-04-02
Affiliations
    1PIGI Lab, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    2Stem Cell and Xenograft Core, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    3Skuli Lab, Division of Hematology/Oncology, University of Cincinnati, College of Medicine, Department of Medicine, Cincinnati, Ohio, USA

Corresponding:

Nicolas Skuli, PIGI Lab, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, 646 BRB Ⅱ/Ⅲ, 421 Curie Boulevard, Philadelphia, PA 19104-6160, USA. Email:
Terence P. Gade,
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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