Differentiation of human induced pluripotent stem cells into erythroid cells
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(2020) 11:483
REVIEW
Open Access
Differentiation of human induced pluripotent stem cells into erythroid cells Mohsen Ebrahimi1, Mehdi Forouzesh2, Setareh Raoufi3, Mohammad Ramazii4, Farhoodeh Ghaedrahmati5 and Maryam Farzaneh6*
Abstract During the last years, several strategies have been made to obtain mature erythrocytes or red blood cells (RBC) from the bone marrow or umbilical cord blood (UCB). However, UCB-derived hematopoietic stem cells (HSC) are a limited source and in vitro large-scale expansion of RBC from HSC remains problematic. One promising alternative can be human pluripotent stem cells (PSCs) that provide an unlimited source of cells. Human PSCs, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are self-renewing progenitors that can be differentiated to lineages of ectoderm, mesoderm, and endoderm. Several previous studies have revealed that human ESCs can differentiate into functional oxygen-carrying erythrocytes; however, the ex vivo expansion of human ESC-derived RBC is subjected to ethical concerns. Human iPSCs can be a suitable therapeutic choice for the in vitro/ex vivo manufacture of RBCs. Reprogramming of human somatic cells through the ectopic expression of the transcription factors (OCT4, SOX2, KLF4, c-MYC, LIN28, and NANOG) has provided a new avenue for disease modeling and regenerative medicine. Various techniques have been developed to generate enucleated RBCs from human iPSCs. The in vitro production of human iPSC-derived RBCs can be an alternative treatment option for patients with blood disorders. In this review, we focused on the generation of human iPSC-derived erythrocytes to present an overview of the current status and applications of this field. Keywords: Induced pluripotent stem cells, Erythrocytes, Reprogramming, Differentiation, Large-scale, Blood disorders
Introduction Blood transfusion is the main therapeutic option and a crucial part of modern medicine for patients with severe anemia [1, 2]. A limited resource of blood, blood group compatibility (ABO and Rh antigens), and the risks of infection can present great challenges for blood transfusion [2, 3]. Therefore, any alternative solution methods would be most helpful for patients with rare blood groups [4]. Mature red blood cells (RBCs) or erythrocytes/erythroid cells in a complex process called erythropoiesis are produced from hematopoietic stem cells * Correspondence: [email protected] 6 Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Full list of author information is available at the end of the article
(HSCs) [5–7]. Erythroblasts (precursors of RBCs) are difficult to proliferate in vitro [2, 8, 9]. In past decades, several groups have generated erythrocytes from umbilical cord blood (UCB)-derived HSCs [2, 10]. Although multipotent HSCs have the capacity for self-renewal, the large-scale in vitro/ex vivo HSCs expansion and differentiation into RBCs is a difficult task [2, 11, 12]. Ex vivo cultured RBCs can also be obtained from i
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