Lost in translation: pluripotent stem cell‐derived hematopoiesis

Abstract

Pluripotent stem cells (PSCs) such as embryonic stem cells or induced pluripotent stem cells represent a promising cell type to gain novel insights into human biology. Understanding the differentiation process of PSCs in vitro may allow for the identification of cell extrinsic/intrinsic factors, driving the specification process toward all cell types of the three germ layers, which may be similar to the human in vivo scenario. This would not only lay the ground for an improved understanding of human embryonic development but would also contribute toward the generation of novel cell types used in cell replacement therapies. In this line, especially the developmental process of mesodermal cells toward the hematopoietic lineage is of great interest. Therefore, this review highlights recent progress in the field of hematopoietic specification of pluripotent stem cell sources. 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.

Leucine-Rich Repeat Kinase 2 Influences Fate Decision of Human Monocytes Differentiated from Induced Pluripotent Stem Cells

“…Surface expression of the hematopoietic lineage marker CD45 and the monocyte marker CD14 [22,39] confirmed successful differentiation of the iPS cells (Fig 1A and 1B). The monocyte population was determined based on the cellular morphology of the recorded iPSC-derived cells, according to their distribution in the scatter plot confirmed by subsequent back-gating (S1A Fig).…”

Generation of HLA-Universal iPSC-Derived Megakaryocytes and Platelets for Survival Under Refractoriness Conditions

“…For differentiation, nontransduced as well as shNS-and shβ2m-expressing Induced pluripotent stem cells (iPSCs) gained plenty of attention in the field of cell therapies including blood pharming, as they may constitute a reliable cell source for the scalable production of several cell types (11). Generally, the use of autologous iPSC-derived grafts has been intended, but the high technical and economic associated efforts constitute a significant hurdle to their clinical application (12).…”

Ex vivo Generation of Genetically Modified Macrophages from Human Induced Pluripotent Stem Cells

“…Results: Use of lentiviral vectors equipped with an ubiquitous chromatin opening element (CBX3-UCOE) as well as zinc finger nuclease-mediated targeting of an expression cassette into the human adeno-associated virus integration site 1 (AAVS1) safe harbor resulted in stable transgene expression in iPSCs. When iPSCs were differentiated along the myeloid pathway into macrophages, both strategies yielded sustained transgene expression during the hematopoietic specification process including mature CD14+ and CD11b+ phoid differentiation or the generation of long-term repopulating hematopoietic stem cells (LTR-HSCs) from human but also murine PSCs is still hampered by the low quality and inefficient quantity of the output cells [2]. The efficient generation of functional mature myeloid cells has been described by several groups utilizing different strategies, which include embryoid body formation, coculture systems as well as small molecule-or cytokine-driven approaches [3][4][5][6].…”