Получение, характеристика и генетическая модификация индуцированных плюрипотентных стволовых клеток крысы для применения в целях тканезаместительной терапии
Диссертация
Полученные иПС клетки крысы, при использовании вирусных векторов с последующим их удалением, обладают нормальным кариотипом и плюрипотентными свойствами. О плюрипотентности полученных иПС клеток свидетельствуют экспрессия в них известных маркеров плюрипотентности (Nanog, Oct4, SSEA1, щелочной фосфатазы), а также способность этих клеток образовать тератомы и участвовать в формировании химерного… Читать ещё >
Содержание
- I. Обзор литературы
- 1. 1. Эмбриональные стволовые клетки
- 1. 1. 1. Основные сигнальные пути, обеспечивающие самообновление клеток и поддержание плюрипотентного состояния в ЭС клетках
- 1. 1. 1. 1. LIF/gpl30/STAT3 — сигнальный путь
- 1. 1. 1. 2. BMP/Smad каскад
- 1. 1. 1. 3. Wnt/p-Catenin/TCF
- 1. 1. 1. 4. Фосфотидилинозитол-3 (PI3) киназный сигнальный путь
- 1. 1. 1. 5. Ras/Raf/ERK сигнальный путь
- 1. 1. 1. 6. Перекрещивание и совместное действие сигнальных путей
- 1. 1. 2. Ключевые транскрипционные факторы, характерные для ЭС клеток, обеспечивающие контроль самоподдержания и плюрипотентного состояния
- 1. 1. 2. 1. Oct
- 1. 1. 2. 2. Nanog
- 1. 1. 2. 3. Sox
- 1. 1. 2. 4. Klf
- 1. 1. 2. 5. сМус
- 1. 1. 3. Эпигенетический статус ЭС клеток
- 1. 1. 4. Влияние химически-синтезированных веществ на ЭС клетки
- 1. 1. 1. Основные сигнальные пути, обеспечивающие самообновление клеток и поддержание плюрипотентного состояния в ЭС клетках
- 1. 2. Индуцированные плюрипотентные стволовые клетки
- 1. 2. 1. Предпосылки открытия феномена индуцированной плюрипотентности
- 1. 2. 2. Открытие феномена индуцированной плюрипотентности
- 1. 2. 3. Необходимые характеристики иПС клеток
- 1. 2. 3. 1. Способы доставки репрограммирующих факторов в клетки: интегрирующие системы
- 1. 2. 3. 2. Способы доставки репрограммирующих факторов в клетки: неинтеграрующие системы
- 1. 2. 3. 3. Идентификация иПС клонов
- 1. 2. 4. Механизмы, лежащие в основе формирования иПС клеток
- 1. 2. 4. 1. Детерминистическая и стохастическая гипотезы перехода соматических клеток в плюрипотентное состояние
- 1. 2. 4. 2. Предполагаемая последовательность событий при переходе клеток в плюрипотентное состояние
- 1. 2. 5. Роль репрограммирующих транскрипционных факторов в процессе перестройки хроматина
- 1. 2. 6. Перспективы использования иПС клеток в терапевтических целях
- 1. 1. Эмбриональные стволовые клетки
- II. 1. Работа с клетками эукариот в культуре
- 1. 2. Обработка МЭФ митомицином
- 1. 10. Получение иПС клеток мыши
- II. 2. Молекулярно-биологические методы
- 11. 2. 1. Генотипирование клонов ЭС (иПС) клеток
- 11. 2. 2. Кариотипирование ЭС (иПС) клеток
- 11. 2. 3. Иммунофлуоресцентное окрашивание клеток, находящихся в культуре
- 11. 2. 4. Реакция обратной транскрипции
- 11. 2. 5. Полимеразная цепная реакция
- 11. 2. 6. LacZ-окрашивание
- 11. 2. 7. Проточная цитофлуореметрия (FACS)
- III. 1. Получение иПС клеток крысы
- 111. 1. 3. Особенности условий культивирования иПС клеток крысы
- III. 2. Метод генетической сенсибилизации
- 111. 2. 1. Создание ДНК конструкций для генетической сенсибилизации
- 111. 2. 2. Генетическая сенсибилизация через введение «маркера-самоубийцы»
- 111. 2. 3. Мечение ТК-ЭС/иПС клеток
- 111. 2. 4. Пример использования генетической сенсибилизации в терапевтических целях
- 111. 2. 4. 1. Участие суицидальных ТК-ЭС клеток в восстановлении функций повреждённой поджелудочной железы
- 111. 2. 4. 2. Участие суицидальных ТК-ЭС клеток в восстановлении гематопоэза у летально облучённых мышей
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