Building the Next Generation of Humanized Hemato-Lymphoid System Mice.
Front Immunol
; 12: 643852, 2021.
Article
en En
| MEDLINE
| ID: mdl-33692812
ABSTRACT
Since the late 1980s, mice have been repopulated with human hematopoietic cells to study the fundamental biology of human hematopoiesis and immunity, as well as a broad range of human diseases in vivo. Multiple mouse recipient strains have been developed and protocols optimized to efficiently generate these "humanized" mice. Here, we review three guiding principles that have been applied to the development of the currently available models (1) establishing tolerance of the mouse host for the human graft; (2) opening hematopoietic niches so that they can be occupied by human cells; and (3) providing necessary support for human hematopoiesis. We then discuss four remaining challenges (1) human hematopoietic lineages that poorly develop in mice; (2) limited antigen-specific adaptive immunity; (3) absent tolerance of the human immune system for its mouse host; and (4) sub-functional interactions between human immune effectors and target mouse tissues. While major advances are still needed, the current models can already be used to answer specific, clinically-relevant questions and hopefully inform the development of new, life-saving therapies.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Madre Hematopoyéticas
/
Trasplante de Células Madre Hematopoyéticas
/
Modelos Animales de Enfermedad
/
Inmunidad Adaptativa
/
Hematopoyesis
Tipo de estudio:
Guideline
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Front Immunol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos