1 Ocak 2018 Dergi makalesi Açık Erişim

Cagnan, Ilgin; Gunel-Ozcan, Aysen; Aerts-Kaya, Fatima; Ameziane, Najim; Kuskonmaz, Baris; Dorsman, Josephine; Gumruk, Fatma; Uckan, Duygu

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    <subfield code="a">Bone Marrow Mesenchymal Stem Cells Carrying FANCD2 Mutation Differ from the Other Fanconi Anemia Complementation Groups in Terms of TGF-beta 1 Production</subfield>
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    <subfield code="a">Transforming growth factor beta (TGF-beta) secretion from cells in the bone marrow (BM) niche affects hematopoietic stem cell (HSC) fate and has a cardinal role in HSC quiescence. BM mesenchymal stem cells (BM-MSCs), a component of the BM niche, may produce abnormal levels of TGF-beta in Fanconi anemia (FA) and may play a role in bone marrow failure. Here, we molecularly and cellularly characterized FA BM-MSCs by addressing their immunophenotype, proliferation- and differentiation- capacity, reactive oxygen species (ROS) production, senescence activity as well as expression and secretion levels of TGF-beta isoforms. In ten FA patients, mutations were detected in FANCA (n = 7), FANCG (n = 1) and FANCD2 (n = 2) genes. The immunophenotype, with the exception of CD29, and differentiation capacity of FA BM-MSCs were similar to healthy donors. FA BM-MSCs showed decreased proliferation, increased ROS level and an arrest in G2 following DEB treatment. beta-galactosidase staining indicated elevated senescence of FANCD2-deficient cells. FA BM-MSCs displayed TGF-beta 1 mRNA levels similar to donor BM-MSCs, and was not affected by DEB treatment. However, secretion of TGF-beta was absent in FA-D2 BM-MSCs. Absence of TGF-beta secretion may be related to early onset of senescence of the FANCD2-deficient BM-MSCs. The proliferative response of FA-D2 BM-MSCs to rTGF-beta 1 was not different from FANCA-deficient and donor cells and raises the possibility that rTGF-beta 1 may reverse the senescence of the FANCD2-deficient BM-MSCs which needs to be investigated further.</subfield>
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    <subfield code="u">Hacettepe Univ, Inst Hlth Sci, Dept Stem Cell Sci, Ctr Stem Cell Res &amp; Dev, TR-06100 Ankara, Turkey</subfield>
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