z-logo
Premium
Ex vivo expansion of human mobilized peripheral blood stem cells using epigenetic modifiers
Author(s) -
Saraf Santosh,
Araki Hiroto,
Petro Benjamin,
Park Youngmin,
Taioli Simona,
Yoshinaga Kazumi G.,
Koca Emre,
Rondelli Damiano,
Mahmud Nadim
Publication year - 2015
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.12904
Subject(s) - trichostatin a , haematopoiesis , stem cell , ex vivo , biology , microbiology and biotechnology , in vivo , immunology , chemistry , cancer research , histone deacetylase , biochemistry , histone , genetics , gene
Background Epigenetic modifications likely control the fate of hematopoietic stem cells ( HSCs ). The chromatin‐modifying agents ( CMAs ), 5‐aza‐2′‐deoxycytidine (5aza D ) and trichostatin A ( TSA ), have previously been shown to expand HSCs from cord blood and marrow. Here we assessed whether CMA can also expand HSC s present in growth factor–mobilized human peripheral blood ( MPB ). Study Design and Methods 5aza D and TSA were sequentially added to CD 34+ MPB cells in the presence of cytokines, and the cells were cultured for 9 days. Results After culture, a 3.6 ± 0.5‐fold expansion of CD 34+ CD 90+ cells, a 10.1 ± 0.5‐fold expansion of primitive colony‐forming unit ( CFU )‐mix, and a 2.2 ± 0.5‐fold expansion of long‐term cobblestone‐area–forming cells ( CAFCs ) was observed in 5aza D / TSA ‐expanded cells. By contrast, cells cultured in cytokines without 5aza D / TSA displayed no expansion; rather, a reduction in CD 34+ CD 90+ cells (0.7 ± 0.1‐fold) and CAFC s (0.3 ± 0.1‐fold) from their initial numbers was observed. Global hypomethylation corresponding with increased transcript levels of several genes implicated in HSC self‐renewal, including HOXB4 , GATA2 , and EZH2 , was observed in 5aza D / TSA ‐expanded MPB cells in contrast to controls. 5aza D / TSA ‐expanded MPB cells retained in vivo hematopoietic engraftment capacity. Conclusion MPB CD 34+ cells from donors can be expanded using 5aza D / TSA , and these expanded cells retain in vivo hematopoietic reconstitution capacity. This strategy may prove to be potentially useful to augment HSC numbers for patients who fail to mobilize.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here