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
Rok vydání: 2017
Předmět:
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