Erythropoiesis In Vitro—A Research and Therapeutic Tool in Thalassemia

Abstract

Thalassemia (thal) is a hereditary chronic hemolytic anemia due to a partial or complete deficiency in the production of globin chains, in most cases, α or β, which compose, together with the iron-containing porphyrins (hemes), the hemoglobin molecules in red blood cells (RBC). The major clinical symptom of β-thal is severe chronic anemia—a decrease in RBC number and their hemoglobin content. In spite of the improvement in therapy, thal still severely affects the quality of life of the patients and their families and imposes a substantial financial burden on the community. These considerations position β-thal, among other hemoglobinopathies, as a major health and social problem that deserves increased efforts in research and its clinical application. These efforts are based on clinical studies, experiments in animal models and the use of erythroid cells grown in culture. The latter include immortal cell lines and cultures initiated by erythroid progenitor and stem cells derived from the blood and RBC producing (erythropoietic) sites of normal and thal donors, embryonic stem cells, and recently, "induced pluripotent stem cells" generated by manipulation of differentiated somatic cells. The present review summarizes the use of erythroid cultures, their technological aspects and their contribution to the research and its clinical application in thal. The former includes deciphering of the normal and pathological biology of the erythroid cell development, and the latter—their role in developing innovative therapeutics—drugs and methods of gene therapy, as well as providing an alternative source of RBC that may complement or substitute blood transfusions.

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“…The significant increase in the hematological parameters with Thypa elephantina (TE.AQ) extract, suggest that it may contain phytochemicals that may activate erythropoietin production in the stem cells of experimental animals. Erythropoietin is a glycoprotein hormone which motivates stem cells in the bone marrow to revenue red blood cells (Fibach, 2019). The present study is in agreement with (Oshilonya, IJioma et al, 2015) who reported the effects of Caulis bambusae (Bamboo) stem extract on hematological and biochemical parameters in chinchilla rabbits (Sun, Yu et al, 2013).…”

Differentiation of human induced pluripotent stem cells into erythroid cells

“…In contrast, human iPSCs have less ethical and social issues compared to human ESCs [24,25]. Human iPSCs are produced by the manipulation of differentiated somatic cells [26][27][28][29]. Reprogramming of human somatic cells through the ectopic expression of transcription factors has provided a new avenue for disease modeling and regenerative medicine [16,30].…”

“…1 ). This developmental procedure is controlled by cell-cell/cell-matrix interactions along with several cytokines and growth factors including IL-3, IL-6, erythropoietin (EPO) (the main erythropoietic stimulating hormone), EPO-receptor, members of the transforming growth factor-β (TGF-β), activin A, activin receptor-II, Flt3 ligand (Flt3-L), vascular endothelial growth factor (VEGF), stem cell factor (SCF), thrombopoietin (TPO), and granulocyte colony-stimulating factor (G-CSF) [ 26 , 41 , 42 ]. Erythropoiesis is controlled and characterized via multiple transcriptional regulators, including myb, Sox6, Bcl11A, Gata1, and Klf1 [ 43 , 44 ].…”

“…Up to date, several culture systems have been established to obtain a sufficient number of mature and functional RBCs in vitro [ 8 ]. Three culture systems including erythroid cells lines (the murine erythroleukemia cell line and the human K562 cell line), HSCs derived from peripheral blood (PB) and UCB, and stem cells (human ESCs, neonatal cord blood (CB), mesenchymal stem cells (MSCs), and human iPSCs) have been evaluated to obtain RBCs [ 26 , 45 ]. An immortalized or continuous cell lines have a homogenous karyotype that can be altered following continuous cell culture, which might not be the most appropriate for pre-clinical studies or clinical applications [ 46 ].…”

Discovery of Novel Fetal Hemoglobin Inducers through Small Chemical Library Screening

“…This investigation resulted in the identification of a subset of compounds that were ultimately analyzed as Hb inducers on primary cell cultures obtained from β -thalassemia patients. This assay has been widely used to validate the HbF-inducing potential of molecules identified using large or middle-scale screening approaches [ 31 , 32 , 33 ].…”