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Production of Humanized Mouse via Thymic Renal Capsule Grafting, CD34+ Cells Injection, and Cytokine Delivery

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Building the Next Generation of Humanized Hemato-Lymphoid System Mice.

Tijana Martinov¹, Kelly M McKenna^1,2,3, Wei Hong Tan¹

¹Clinical Research Division, Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.

Frontiers in Immunology

|March 11, 2021

Summary

Humanized mice, engrafted with human hematopoietic cells, are crucial for studying human diseases and immunity. Current models show promise but face challenges in immune development and host tolerance.

Keywords:

cancer hematopoiesis humanized mice immunity immunotherapies infectious diseases

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Area of Science:

Immunology
Hematology
In vivo disease modeling

Background:

Mice repopulated with human hematopoietic cells since the 1980s.
Used to study human hematopoiesis, immunity, and diseases in vivo.
Multiple mouse strains and protocols developed for efficient generation of humanized mice.

Purpose of the Study:

Review guiding principles in developing humanized mouse models.
Discuss remaining challenges and limitations in current models.
Highlight the utility of existing models for clinical research.

Main Methods:

Review of established principles for creating humanized mice.
Analysis of challenges in human hematopoietic lineage development and immune function.
Evaluation of host-engraftment tolerance and immune system interactions.

Main Results:

Three key principles: host tolerance, niche availability, and hematopoietic support.
Four challenges: poor lineage development, limited adaptive immunity, absent host tolerance, and functional deficits.
Current models can address specific clinical questions.

Conclusions:

Humanized mice are valuable tools for biomedical research.
Further advances are needed to overcome current limitations.
Existing models can inform the development of novel therapies.