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Definitive Erythropoiesis from Pluripotent Stem Cells: Recent Advances and Perspectives

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Cell Biology and Translational Medicine, Volume 3

Part of the book series: Advances in Experimental Medicine and Biology ((CBTMED,volume 1107))

Abstract

Derivation of functional and mature red blood cells (RBCs) with adult globin expression from renewable source such as induced pluripotent stem cells (iPSCs) is of importance from the clinical point of view. Definitive RBC generation can only be succeeded through production of true hematopoietic stem cells (HSCs). There has been a great effort to obtain definitive engraftable HSCs from iPSCs but the results were mostly unsatisfactory due to low, short-term and linage-biased engraftment in mouse models. Moreover, ex vivo differentiation approaches ended up with RBCs with mostly embryonic and fetal globin expression. To establish reliable, standardized and effective laboratory protocols, we need to expand our knowledge about developmental hematopoiesis/erythropoiesis and identify critical regulatory signaling pathways and transcription factors. Once we meet these challenges, we could establish differentiation protocols for massive RBC production for transfusion purposes in the clinical setting, performing drug screening and disease modeling in ex vivo conditions, and investigating the embryological cascade of erythropoiesis. More interestingly, with the introduction of relatively efficient and facile genome editing tools, genetic correction for inherited RBC disorders such as sickle cell disease (SCD) would become possible through iPSCs that can subsequently generate definitive HSCs, which then give rise to definitive RBCs producing β-globin after transplantation.

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Abbreviations

AGM:

Aorta-gonad-mesonephros

BMPs:

Bone morphogenetic proteins

BMT:

Bone marrow transplantation

EBs:

Embryoid bodies

EHT:

Endothelial-to-hematopoietic transition

EMPs:

Erythromyeloid progenitors

EryD:

Definitive erythrocytes

EryP:

Primitive erythrocytes

ESCs:

Embryonic stem cells

FGF2:

Fibroblast growth factor 2

FLT-3:

Fms-like tyrosine kinase 3

HLA:

Human leukocyte antigen

HSCs:

Hematopoietic stem cells

ILs:

Interleukins

iPSCs:

Induced pluripotent stem cells

RBCs:

Red blood cells

SCD:

Sickle cell disease

SCF:

Stem cell factor

TPO:

Thrombopoietin

VEGF:

Vascular endothelial growth factor

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The authors have no commercial, proprietary, or financial interest in the products described in this article.

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  1. Molecular and Clinical Hematology Branch, National Heart Lung and Blood Institutes (NHLBI), Bethesda, MD, USA

    Selami Demirci & John F. Tisdale

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  1. Selami Demirci
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Correspondence to Selami Demirci or John F. Tisdale .

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  1. Ottawa Hospital Research Institute, Osgoode, ON, Canada

    Kursad Turksen

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Demirci, S., Tisdale, J.F. (2018). Definitive Erythropoiesis from Pluripotent Stem Cells: Recent Advances and Perspectives. In: Turksen, K. (eds) Cell Biology and Translational Medicine, Volume 3. Advances in Experimental Medicine and Biology(), vol 1107. Springer, Cham. https://doi.org/10.1007/5584_2018_228

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