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FGF-2 expands murine hematopoietic stem and progenitor cells via proliferation of stromal cells, c-Kit activation, and CXCL12 down-regulationстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 21 мая 2019 г.
- Авторы: Itkin T., Ludin A., Gradus B., Gur-Cohen S., Kalinkovich A., Schajnovitz A., Ovadya Y., Kollet O., Canaani J., Shezen E., Coffin D.J., Enikolopov G.N., Berg T., Piacibello W., Hornstein E., Lapidot T.
- Журнал: Blood
- Том: 120
- Номер: 9
- Год издания: 2012
- Издательство: American Society of Hematology
- Местоположение издательства: United States
- Первая страница: 1843
- Последняя страница: 1855
- DOI: 10.1182/blood-2011-11-394692
- Аннотация: Cytokine-induced expansion of hematopoietic stem and progenitor cells (HSPCs) is not fully understood. In the present study, we show that whereas steady-state hematopoiesis is normal in basic fibroblast growth factor (FGF-2)-knockout mice, parathyroid hormone stimulation and myeloablative treatments failed to induce normal HSPC proliferation and recovery. In vivo FGF-2 treatment expanded stromal cells, including perivascular Nestin + supportive stromal cells, which may facilitate HSPC expansion by increasing SCF and reducing CXCL12 via mir-31 up-regulation. FGF-2 predominantly expanded a heterogeneous population of undifferentiated HSPCs, preserving and increasing durable short- and long-term repopulation potential. Mechanistically, these effects were mediated by c-Kit receptor activation, STAT5 phosphorylation, and reduction of reactive oxygen species levels. Mice harboring defective c-Kit signaling exhibited abrogated HSPC expansion in response to FGF-2 treatment, which was accompanied by elevated reactive oxygen species levels. The results of the present study reveal a novel mechanism underlying FGF-2-mediated in vivo expansion of both HSPCs and their supportive stromal cells, which may be used to improve stem cell engraftment after clinical transplantation. © 2012 by The American Society of Hematology.
- Добавил в систему: Ениколопов Григорий Николаевич