Age effects on angiogenic properties of adipose tissue mesenchymal stem cells



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Abstract

Мезенхимальные стволовые клетки жировой ткани
(МСК-ЖТ) способны стимулировать ангиогенез посред-
ством продукции факторов роста и стабилизации растущих
сосудов. МСК-ЖТ являются перспективным материалом
для аутологичной клеточной терапии. Однако с возрас-
том пациентов активность их МСК-ЖТ, а, следовательно, и
эффективность клеточной терапии могут снижаться. Целью
нашей работы было оценить ангиогенные свойства МСК-ЖТ
при старении.
Материал и методы. МСК-ЖТ были выделены из под-
кожной жировой ткани мышей линии BalB/с возраста 1-2,
12, 18 и 24 мес., а также 12 доноров трех возрастных
групп (12 (5; 12) лет, 45 (41; 45) лет и 65 (59; 76) лет).
МСК-ЖТ 2-го пассажа помещали на 48 ч в условия 1%
или 20% содержания кислорода. Оценивали способность
клеток стимулировать ангиогенез in vitro и in vivo.
Результаты. Способность МСК-ЖТ мышей стимулиро-
вать формирование капилляроподобных структур in vitro и
васкуляризацию подкожных имплантатов Матригеля in vivo
с возрастом снижалась в среднем на 60%. Содержание
мРНК сосудистого эндотелиального фактора роста (VEGF)
и плацентарного фактора роста (PlGF) в этих клетках сни-
жалось, а фактора роста гепатоцитов (HGF) и компонентов
системы внеклеточного протеолиза (рецептор к урокиназе,
металлопротеиназы 2 и 9 типов, ингибитор активатора
плазминогена-1) - возрастало с возрастом животных. Сти-
муляция экспрессии VEGF, PlGF и HGF в условиях гипоксии
была выражена слабее в случае МСК-ЖТ старых живот-
ных. Экспрессия PlGF и ангиопоэтина-1, а также секреция
VEGF и HGF МСК-ЖТ человека отрицательно коррелирова-
ли с возрастом донора.
Таким образом, при старении способность МСК-ЖТ сти-
мулировать ангиогенез снижается в результате подавления
экспрессии ключевых ангиогенных факторов.

About the authors

A Yu Efimenko,

M.V. Lomonosov Moscow State University, Moscow

M.V. Lomonosov Moscow State University, Moscow

E E Starostina,

M.V. Lomonosov Moscow State University, Moscow

M.V. Lomonosov Moscow State University, Moscow

N I Kalinina,

M.V. Lomonosov Moscow State University, Moscow

M.V. Lomonosov Moscow State University, Moscow

E V Parfyenova

M.V. Lomonosov Moscow State University, Moscow

M.V. Lomonosov Moscow State University, Moscow

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