Development of hematopoietic stem cells from human ES and iPS cells

• Applicant: Dr. Katharina Hartmann
• Subject Area: Hematology, Oncology
• Term: from 2011 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 207511694

The ability to generate hematopoietic stem cells (HSCs) in vitro from embryonic stem (ES) and induced pluripotent stem (iPS) cells would allow replacement of defective hematopoietic cells without the need of human leukocyte antigen (HLA)-matching donors. Several studies have shown that mature hematopoietic cells can be successfully developed in vitro from ES and iPS cells. However, the in vitro generation and maintenance of HSCs, which can reconstitute the whole hematopoietic system in vivo, remains still challenging.The aim of the proposed project is to find optimal culture conditions in order to develop HSCs rather than mature hematopoietic cells in vitro from human ES and iPS cells in a system using stromal cell lines. It has been shown that the microenvironment and the time frame influence the development of HSCs in vitro. Hence, different stromal cell lines and time plans will be applied. Surface marker analyses and subsequent cell sorting of the differentiating cells will allow to enrich HSCs and to deplete undifferentiated cells with teratogenic potential in the culture.Recently, the group of Prof. Weissman identified genes that are differentially expressed in reconstituting HSCs versus non-reconstituting hematopoietic progenitors. Those candidate genes, which may favor the development of HSCs from ES and iPS cells, will be overexpressed using retroviral vectors carrying cDNA. Alternatively, mRNA of the candidate genes will be administered. The influence of these genes will be analyzed by in vitro differentiation and in vivo reconstitution assays. Finally, upon successful hematopoietic reconstitution the ability to tolerate syngenic and allogenic organ transplants will be investigated.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Irving L. Weissman