Hematopoietic progenitor cells in the blood and bone marrow in various hematologic disorders

Issaragrisil, Surapol; U-Pratya, Yaowalak; Yimyam, M.; Pakdeesuwan, Kriangsak; Khuhapinant, Archrob; Muangsup, Wanna; Pattanapanyasat, Kovit

doi:10.1002/stem.5530160815

Cited by 7 publications

(3 citation statements)

References 26 publications

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“…In thal, the number of EPC and their ability to develop in culture is much increased, especially in splenectomized patients [56]. There is a positive correlation between the number of colony-developing EPC and the number of circulating nucleated RBC (normoblasts).…”

Section: Clinical Diagnosismentioning

confidence: 99%

Erythropoiesis In Vitro—A Research and Therapeutic Tool in Thalassemia

Fibach

2019

JCM

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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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Section: Clinical Diagnosismentioning

confidence: 99%

Erythropoiesis In Vitro—A Research and Therapeutic Tool in Thalassemia

Fibach

2019

JCM

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“…Erythrocyte colony-forming units (CFU-Es) are Stem Cell Factor (SCF) and Erythropoietin (EPO)-responsive erythroid progenitors present in the liver and bone marrow (BM) during, respectively, fetal and adult life. Since CFU-Es can be propagated and differentiated into red blood cells (RBCs), they are important potential targets not only for the treatment of anemia [1][2][3] but also for the manufacture of RBCs ex vivo for transfusion. 4 Fetal and adult erythropoiesis is a tightly coordinated multistep developmental process that involves the differentiation of hematopoietic stem cells to lineage-restricted erythroid progenitors that subsequently undergo terminal differentiation to give rise to RBCs.…”

Section: Introductionmentioning

confidence: 99%

Biochemical measurements on single erythroid progenitor cells shed light on the combinatorial regulation of red blood cell production

2013

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Adult bone marrow (BM) erythrocyte colony-forming units (CFU-Es) are important cellular targets for the treatment of anemia and also for the manufacture of red blood cells (RBCs) ex vivo. We obtained quantitative biochemical measurements from single and small numbers of CFU-Es by isolating and analyzing c-Kit(+)CD71(high)Ter119(-) cells from adult mouse BM and this allowed us to identify two mechanisms that can be manipulated to increase RBC production. As expected, maximum RBC output was obtained when CFU-Es were stimulated with a combination of Stem Cell Factor (SCF) and Erythropoietin (EPO) mainly because SCF supports a transient CFU-E expansion and EPO promotes the survival and terminal differentiation of erythroid progenitors. However, we found that one of the main factors limiting the output in RBCs was that EPO induces a downregulation of c-Kit expression which limits the transient expansion of CFU-Es. In the presence of SCF, the EPO-mediated downregulation of c-Kit on CFU-Es is delayed but still significant. Moreover, treatment of CFU-Es with 1-Naphthyl PP1 could partially inhibit the downregulation of c-Kit induced by EPO, suggesting that this process is dependent on a Src family kinase, v-Src and/or c-Fyn. We also found that CFU-E survival and proliferation was dependent on the level of time-integrated extracellular-regulated kinase (ERK) activation in these cells, all of which could be significantly increased when SCF and EPO were combined with mouse fetal liver-derived factors. Taken together, these results suggest two novel molecular strategies to increase RBC production and regeneration.

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“…Circulating erythroid–burst‐forming units (BFU‐E) have been determined in patients with β‐TM, more recently in the context of gene therapy studies . A significant increase of circulating erythroid progenitor cells (three to five times more than normal) has been reported in thalassemia, with a linear relationship between the number of BFU‐E and CFU .…”

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confidence: 99%