Lost in translation: pluripotent stem cell-derived hematopoiesis.
Bottom Line: In addition, we would like to shed light on emerging factors controlling primitive and definitive hematopoietic development and to highlight recent approaches to improve the differentiation potential of PSC sources toward hematopoietic stem/progenitor cells.While the generation of fully defined hematopoietic stem cells from PSCs remains challenging in vitro, we here underline the instructive role of cell extrinsic factors such as cytokines for the generation of PSC-derived mature hematopoietic cells.Thus, we have comprehensively examined the role of cytokines for the derivation of mature hematopoietic cell types such as macrophages, granulocytes, megakaryocytes, erythrocytes, dendritic cells, and cells of the B- and T-cell lineage.
Affiliation: RG Reprogramming and Gene Therapy, REBIRTH Cluster of Excellence Hannover Medical School, Hannover, Germany Institute of Experimental Hematology Hannover Medical School, Hannover, Germany.Show MeSH
Mentions: During mammalian embryonic development, the emergence of definitive hematopoietic “stem” cells characterized by their potential to generate B- and T-lymphoid cells as well as to repopulate an irradiated host is preceded by a wave of primitive hematopoiesis (Yoder, 2014). In this line, inducing a definitive hematopoietic program during the in vitro differentiation process of PSCs may resemble the prerequisite to generate HSCs with long-term engraftment potential. Probably, this switch from the primitive to definitive hematopoiesis represents the bottleneck that is hindering the efficient long-term engraftment potential of PSC-derived hematopoietic stem/progenitor cells (HSPCs) so far (Szabo et al, 2010; Ran et al, 2013) (see also Fig2).
Affiliation: RG Reprogramming and Gene Therapy, REBIRTH Cluster of Excellence Hannover Medical School, Hannover, Germany Institute of Experimental Hematology Hannover Medical School, Hannover, Germany.