TGFβ Inhibitor A83-01 Enhances Murine HSPC Expansion for Gene Therapy.

ABSTRACT: Murine hematopoietic stem and progenitor cells (HSPCs) are commonly used as model systems during gene therapeutic retroviral vector development and preclinical biosafety assessment. Here, we developed cell culture conditions to maintain stemness and prevent differentiation during HSPC culture. We used the small compounds A83-01, pomalidomide, and UM171 (APU). Highly purified LSK SLAM cells expanded in medium containing SCF, IL-3, FLT3-L, and IL-11 but rapidly differentiated to myeloid progenitors and mast cells. The supplementation of APU attenuated the differentiation and preserved the stemness of HSPCs. The TGFβ inhibitor A83-01 was identified as the major effector. It significantly inhibited the mast-cell-associated expression of FcεR1α and the transcription of genes regulating the form

SUBMITTER: Fleischauer J 

PROVIDER: S-EPMC10416825 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature