UM171 Expands Distinct Types of Myeloid and NK Progenitors from Human Pluripotent Stem Cells

Overview

Journal Sci Rep

Specialty Science

Date 2019 May 1

PMID 31036928

Citations 18

Authors

Walatta-Tseyon Mesquitta

Matthew Wandsnider

Hyunjun Kang

James Thomson

Oleg Moskvin

Kran Suknuntha

Igor I Slukvin

Affiliations

Soon will be listed here.

Abstract

Scaling up blood cell production from hPSCs is critical to advancing hPSC technologies for blood transfusion, immunotherapy, and transplantation. Here we explored the potential of the HSC agonist pyrimido-indole derivative UM171, to expand hematopoietic progenitors (HPs) derived from hPSCs in chemically defined conditions. We revealed that culture of hPSC-HPs in HSC expansion conditions (SFEM with added TPO, SCF, FLT3L, IL3 and IL6) in the presence of UM171 predominantly expanded HPs with a unique CD34CD41aCD45 phenotype that were enriched in granulocytic progenitors (G-CFCs). In contrast, in lymphoid cultures on OP9-DLL4, in the presence of SCF, FLT3L, and IL7, UM171 selectively expanded CD34CD45CD7 lymphoid progenitors with NK cell potential, and increased NK cell output up to 10-fold. These studies should improve our understanding of the effect of UM171 on de novo generated HPs, and facilitate development of protocols for robust granulocyte and lymphoid cell production from hPSCs, for adoptive immunotherapies.

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