Scientists at the University of Wisconsin-Madison report that they were able to transform human embryonic stem cells (hESCs) into progenitors of white blood cells and into six types of mature white blood and immune cells. They say that the technique works equally well with stem cells grown from an embryo and with adult pluripotent stem cells that have been converted until they resemble embryonic stem cells.
The study is detailed in a paper titled “Generation of mature human myelomonocytic cells through expansion and differentiation of pluripotent stem cell–derived lin–CD34+CD43+CD45+ progenitors,” appearing in The Journal of Clinical Investigation.
Typically such research 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, the researchers explain. To overcome these limitations, they developed a protocol for generation of neutrophils, eosinophils, macrophages, osteoclasts, dendritic cells, and Langerhans cells from hESCs.
First they generated lin–CD34+CD43+CD45+ hematopoietic cells highly enriched in myeloid progenitors through co-culture of hESCs. 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. Additionally, the team says that a similar protocol could be used to generate myelomonocytic cells from induced pluripotent stem cells.
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, the investigators note.
“While we now can make almost all types of blood cells from embryonic and adult pluripotent stem cells, the next major challenge is to produce blood stem cells that might be used in a bone marrow transplant,” says study leader Igor Slukvin, M.D., Ph.D., an assistant professor in the university's department of pathology and laboratory medicine.
Additionally, Dr. Slukvin expects the new technique to produce cells that model a variety of medical conditions. “We can take cells from patients with a disease of the blood system and explore the cause and treatment of that specific disease. We can generate blood cells which are normal or abnormal and study the mechanisms and treatments of blood cancers.”