Abstract
Research laboratories in various countries are constantly endeavouring to improve the existing and to create new biological objects to simulate various human diseases. Immunodefi cient mice with transplanted human functional cells and tissues, as well as transgenic animals with the relevant human genes integrated in their genome — i. e. humanized mice — are increasingly used as test systems in biomedical studies. Humanized mouse models are constantly being improved to fi nd application in studies investigating human biological reactions and identifying the pathogenetic mechanisms behind a wide range of diseases, or as preclinical tools for medicine testing. In particular, such animals play an increasingly important role both in studies of human-specifi c infectious agents, cancer biology research and in the development of new antitumour agents. In addition, humanized mice are increasingly used as translational models in many areas of clinical research, including transplantology, immunology and oncology. Ultimately, the use of humanized animals can lead to the introduction of a truly personalized medicine into clinical practice. In this review, we discuss modern advances in the creation and use of humanized mice, emphasizing their usefulness for the pathogenesis study, as well as the development of new methods for human cancer treatment.
Highlights
В лабораториях разных стран ведется постоянная работа по улучшению существующих, а также созданию новых биологических объектов, моделирующих различные заболевания человека
Immunodeficient mice with transplanted human functional cells and tissues, as well as transgenic animals with the relevant human genes integrated in their genome — i. e. humanized mice — are increasingly used as test systems in biomedical studies
Humanized mice are increasingly used as translational models in many areas of clinical research, including transplantology, immunology and oncology
Summary
Процесс трансплантации донорского материала обычно включает следующие этапы. 1. Авторами проведенного исследования было заявлено о перспективности применения моделей Balb/c Rag-2-/-Jak3-/и их преимуществах перед иммунодефицитами NOD/scid-мышей [23]. При выборе возрастной категории животных для гуманизации — новорожденных (1–5, в крайнем случае 7 сут) или взрослых (от 5 нед.) — исследователи, как правило, руководствуются следующими практическими соображениями: 1. Важнейшим из этих условий является иммуносупрессия, необходимая для предупреждения реакции трансплантата против хозяина, или отторжения иммунной системой реципиента клеток или тканей, поступивших из донорского организма. Для кондиционирования новорожденных мышат BALB/c используют дозы γ-облучения от 3до 4 Гр, тогда как взрослых (8–10 недель) — 5 Гр соответственно. Описан режим кондиционирования новорожденных мышей BALB/c-Rag-2 /IL2rγnull суммарной дозой 4 Гр (по 2 Гр с интервалом 3–4 ч) и с последующим ожиданием в течение 4–12 ч до инокуляции человеческих ГСК [40]
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