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Definitive Erythropoiesis from Pluripotent Stem Cells: Recent Advances and Perspectives

  • Selami Demirci
  • John F. Tisdale
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, 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.

Keywords

Embryonic stem cells Erythrocytes Hemogenic endothelium β-Globin 

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

Notes

Conflicts of Interest

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

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Molecular and Clinical Hematology BranchNational Heart Lung and Blood Institutes (NHLBI)BethesdaUSA

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