Характеристика ckit позитивных резидентных стволовых клеток миокарда у больных ишемической болезнью сердца тема диссертации и автореферата по ВАК РФ 03.01.04, кандидат медицинских наук Дергилев, Константин Владимирович

• Дергилев, Константин Владимирович
• кандидат медицинских наук
• 2011

Оглавление диссертации кандидат медицинских наук Дергилев, Константин Владимирович

СПИСОК СОКРАЩЕНИЙ

АКТУАЛЬНОСТЬ ПРОБЛЕМЫ

НАУЧНАЯ НОВИЗНА

ПРАКТИЧЕСКАЯ ЗНАЧИМОСТЬ

ВНЕДРЕНИЕ В ПРАКТИКУ

ОБЗОР ЛИТЕРАТУРЫ

Регенеративный потенциал сердца

Применение стволовых клеток для лечения болезней сердечнососудистой системы

Клеточная терапия инфаркта миокарда

Клеточная терапия хронической ИБС и постинфарктной сердечной недостаточности

Резидентные стволовые клетки сердца

Islet-1 клетки

Sp-популяция

С—kit позитивные клетки

Клетки, образующие кардиосферы

Sca-1 клетки

Клеточная ниша

Активация стволовых клеток сердца

Перспективы примения стволовых клеток сердца для регенерации миокарда

Стволовые клетки сердца при патологии миокарда и старении

Стволовые клетки сердца при остром инфаркте миокарда и отдаленном постинфарктном периоде

Стволовые клетки сердца при диабетической кардиомиопатии

Старение миокарда и стволовые клетки сердца

Заключение диссертации по теме «Биохимия», Дергилев, Константин Владимирович

выводы

1. В миокарде ушка ПП, аневризмы у больных ИБС и в неповрежденном миокарде присутствуют с—кк+ клетки, характеризующиеся экспрессией маркеров стволовых клеток (ШЖ1, С-те!;, ЮБ-Ш, 1Ч-кадгерин) и отсутствием гематопоэтических маркеров (СБ34, СБ45); количество этих клеток в неповрежденном миокарде обратно коррелирует с возрастом (г — 0,78; р<0,0001).

2. В миокарде ушка ПП больных ИБС и в неповрежденном миокарде часть с-кй+ стволовых клеток сердца пролиферирует и дифференцируется в клетки-предшественники кардиомиоцитов и гладкомышечных клеток; в ткани аневризмы ЛЖ с-кй+ клетки не пролиферируют, не экспрессируют маркеров дифференцировки в кардиомиоциты и клетки сосудов и экспрессируют ингибитор клеточного цикла р21 С1рА¥аГ1.

3. Количество с-кй+ клеток в миокарде ушка ПП наибольшее у женщин моложе 60 лет, оно положительно коррелирует с выраженностью атеросклероза коронарных артерий и дилатации ЛП, но не зависит от наличия факторов риска сердечно-сосудистых заболеваний (артериальной гипертонии, сахарного диабета, гиперлипидемии, ожирения, курения) и ИМ в анамнезе.

4. Разработанная методика, сочетающая использование метода эксплантной культуры и последующей иммуномагнитной селекции, позволяет получить обогащенную культуру с-кй+ СКС из операционных образцов миокарда человека.

5. Пролиферативный потенциал культивируемых c-kit+ клеток, получаемых из ткани ушка ПП выше, чем у клеток, получаемых из ткани аневризмы; культивируемые c-kit+ клетки ушка ПП обладают клоногенностью и экспрессируют гены плюрипотентности (Oct4, Sox2, Klf4, C-myc, Nanog).

6. Культивируемые c-kit+ клетки ушка ПП могут быть индуцированы к начальным этапам кардиомиоцитарной дифференцировки и к эндотелиальной дифференцировке, способны формировать капилляроподобные структуры in vitro и секретируют ангиогенные факторы роста (VEGF и HGF); c-kit+ клетки, полученные из аневризмы, способны только к начальным этапам кардиомиоцитарной дифференцировки.

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