Ex Vivo Expansion of CD34
Autor: | Sudipto, Bari, Qixing, Zhong, Xiubo, Fan, Zhiyong, Poon, Alvin Soon Tiong, Lim, Tse Hui, Lim, Niraja, Dighe, Shang, Li, Gigi Ngar Chee, Chiu, Christina Li Lin, Chai, William Ying Khee, Hwang |
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Rok vydání: | 2017 |
Předmět: |
Azoles
Pyridines Cord Blood Azole‐based small molecules Hematopoietic stem and progenitor cells Ex vivo expansion Antigens CD34 Hematopoietic stem cell transplantation Mice SCID Xenotransplantation with immunodeficient mouse model Integrin alpha6 Small Molecule Libraries Mice Structure-Activity Relationship Umbilical cord blood Translational Research Articles and Reviews Animals Cells Cultured Stem Cells Imidazoles Cord / Cord Blood Stem Cells (WJ-MSCs) Fetal Blood Hematopoietic Stem Cells Small Molecule Based Reprograming Hematopoietic Stem/Progenitor Cells Thy-1 Antigens Hematopoietic Regeneration Cell Culture Advances |
Zdroj: | Stem Cells Translational Medicine |
ISSN: | 2157-6564 |
Popis: | Umbilical cord blood (UCB) transplants in adults have slower hematopoietic recovery compared to bone marrow (BM) or peripheral blood (PB) stem cells mainly due to low number of total nucleated cells and hematopoietic stem and progenitor cells (HSPC). As such in this study, we aimed to perform ex vivo expansion of UCB HSPC from non‐enriched mononucleated cells (MNC) using novel azole‐based small molecules. Freshly‐thawed UCB–MNC were cultured in expansion medium supplemented with small molecules and basal cytokine cocktail. The effects of the expansion protocol were measured based on in vitro and in vivo assays. The proprietary library of >50 small molecules were developed using structure‐activity‐relationship studies of SB203580, a known p38‐MAPK inhibitor. A particular analog, C7, resulted in 1,554.1 ± 27.8‐fold increase of absolute viable CD45+CD34+CD38–CD45RA– progenitors which was at least 3.7‐fold higher than control cultures (p 600‐fold expansion of CD34+/CD90+/CD49f+ rare HSPCs coupled with significant (p |
Databáze: | OpenAIRE |
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