Generation of mature human myelomonocytic cells through expansion and differentiation of pluripotent stem cell-derived lin-CD34+CD43+CD45+ progenitors

Basic research into human mature myelomonocytic cell function, myeloid lineage diversification and leukemic transformation, and assessment of myelotoxicity in preclinical drug development requires a constant supply of donor blood or bone marrow samples and laborious purification of mature myeloid ce...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of clinical investigation 2009-09, Vol.119 (9), p.2818-2829
Main Authors: Choi, Kyung-Dal, Vodyanik, Maxim A, Slukvin, Igor I
Format: Article
Language:English
Subjects:
Antigens, CD34 - metabolism
Cell Differentiation - drug effects
Cells, Cultured
Coculture Techniques
Embryonic Stem Cells - cytology
Embryonic Stem Cells - drug effects
Embryonic Stem Cells - metabolism
Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology
Humans
Leukocyte Common Antigens - metabolism
Leukosialin - metabolism
Myeloid Cells - cytology
Myeloid Cells - drug effects
Myeloid Cells - metabolism
Phenotype
Pluripotent Stem Cells - cytology
Pluripotent Stem Cells - drug effects
Pluripotent Stem Cells - metabolism
Recombinant Proteins
Technical Advance
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Basic research into human mature myelomonocytic cell function, myeloid lineage diversification and leukemic transformation, and assessment of myelotoxicity in preclinical drug development requires a constant supply of donor blood or bone marrow samples and laborious purification of mature myeloid cells or progenitors, which are present in very small quantities. To overcome these limitations, we have developed a protocol for efficient generation of neutrophils, eosinophils, macrophages, osteoclasts, DCs, and Langerhans cells from human embryonic stem cells (hESCs). As a first step, we generated lin-CD34+CD43+CD45+ hematopoietic cells highly enriched in myeloid progenitors through coculture of hESCs with OP9 feeder cells. After expansion in the presence of GM-CSF, these cells were directly differentiated with specific cytokine combinations toward mature cells of particular types. Morphologic, phenotypic, molecular, and functional analyses revealed that hESC-derived myelomonocytic cells were comparable to their corresponding somatic counterparts. In addition, we demonstrated that a similar protocol could be used to generate myelomonocytic cells from induced pluripotent stem cells (iPSCs). This technology offers an opportunity to generate large numbers of patient-specific myelomonocytic cells for in vitro studies of human disease mechanisms as well as for drug screening.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI38591