
(AGENPARL) – lun 15 luglio 2024 Cari tutti,
so che siamo tutti sommersi con il Vertice NATO ma vi segnalo il lavoro di questo scienziato italiano, Prof. Paolo Casali, un “top Italian scientist”, immunologo, che lavora in Texas. Casali ha pubblicato su Nature uno studio davvero innovativo su “topi umanizzati”. In poche parole, i topi di laboratorio vengono “modificati” affinché diventino quanto più’ simili al corpo umano. In questo modo i vari test su di essi possono diventare ancora più affidabili.
Credo sia la prima volta in assoluto su questo tema. E il fatto che ci sia un italiano alla guida di tale progetto ci fa onore.
Il prof. Casali vorrebbe far arrivare la notizia alla stampa italiana.
Lo trovate a questo link:
Scientists create first mouse model with complete, functional human immune system
Qui il link della sua BIO:
Qui sotto altre informazioni sulla sua ricerca:
About our paper reporting the generation of a new and advanced humanized mouse and related invited Nature Portfolio commentary, to be published in July (vol 25:6) issue of Nature Immunology, on Tuesday, June 25.
Mice have been widely used as in vivo mammalian models due to their small size, ease of maintenance and handling, short reproductive cycle, sharing of genomic and physiological properties with humans and ability to be readily manipulated genetically. Many of the more the 1600 immune response mouse genes, however, are incongruent with their human equivalents, resulting in divergencies or deficiencies of mice as predictors of human immune responses, making availability of a “humanized” mouse model that faithfully reproduces human immune responses a high priority.
There has been a long quest for a humanized mouse capable of mounting specific, fully mature immune, particularly antibody responses. Yet, such a humanized mouse has yet to be established. Maturation of the antibody response entails B cell somatic hypermutation (SHM), class-switch DNA recombination (CSR), differentiation of plasma cells (PCs) making high-affinity antibodies and generation of specific memory B cells (MBCs). The National Institutes of Health, National Institute of Allergy and Infectious Diseases emphasized the need for a novel and more advanced human immune system mouse model (Allen et al., Humanized immune system mouse models: progress, challenges and opportunities. Nature Immunol 20, 770-774, 2019), a recommendation, however, that has gone essentially unheeded.
We constructed humanized THX mice by grafting intracardiacally newborn immunodeficient c-KitW41 mutant mice with human CD34+ cord blood hematopoietic stem cells (HSCs) and submitted the grafted mice to a regimen of hormonal conditioning. Adult THX mice develop a 100% human immune system with well-formed secondary lymphoid organs, including well-developed thymus (containing human thymic epithelial cells), peripheral lymph nodes, Peyer’s patches, etc., maturing human T cells, B cells, marginal zone B cells, memory B cells, NK cells, dendric cells, monocytes/macrophages and granulocytes. THX mice mount class-switched and somatically hypermutated mature antibody responses to T-dependent and T-independent conjugated haptens, and vigorous mature and neutralizing human antibody responses to Salmonella and SARS-CoV-2 RBD upon vaccination with purified S. flagellin and Pfizer COVID-19 mRNA, as accompanied by blood incretion of human cytokines, including APRIL, BAFF, TGF-•• IL-4 and IFN-•, at physiological levels, and generation of specific memory B cells and plasma cells. Finally, they develop lupus autoimmunity after pristane injection. TruHuX (THX) mice (US, CA, EU patent pending) are the very first truly humanized mice.
Thus, by critically leveraging estrogen activity to support human HSC and human immune cell differentiation and maturation of antibody responses, THX mice provide a platform for human immune system studies, development of human vaccines and testing of therapeutics.
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