Banking of Pluripotent Adult Stem Cells as an Unlimited Source for Red Blood Cell Production: Potential Applications for Alloimmunized Patients and Rare Blood Challenges

Peyrard, Thierry; Bardiaux, L.; Krause, C.; Kobari, Ladan; Lapillonne, Hélène; Andreu, G.; Douay, Luc

doi:10.1016/j.tmrv.2011.01.002

Cited by 72 publications

(83 citation statements)

References 49 publications

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“…31 The approach we now report provides an alternative to functional normalization of sickle cell RBC for auto transfusion purposes in the hiPSC model. 5,11,15 In conclusion, using the model of hematopoiesis, we show for the first time that hiPSC can achieve terminal maturation, in vitro in terms of enucleation and in vivo in terms of synthesis of adult Hb. Furthermore, the data for SCD suggest that hiPSC could represent a very valuable model system to study genetic disorders of erythropoiesis.…”

Section: Discussionmentioning

confidence: 64%

“…15 We recently established the proof of principle for transfusion of in vitro generated enucleated RBC in humans. 31 The approach we now report provides an alternative to functional normalization of sickle cell RBC for auto transfusion purposes in the hiPSC model.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the data for SCD suggest that hiPSC could represent a very valuable model system to study genetic disorders of erythropoiesis. Since iPSC cells can proliferate indefinitely and can be selected for a phenotype of interest, 5,11,15 they are potential candidates to organize complementary sources of RBCs for transfusion. However, the procedures need to be optimized before their use in clinical practice can be considered.…”

Section: Discussionmentioning

confidence: 99%

“…6,13,14 Our previous studies have demonstrated the possibility of generating enucleated erythrocytes containing functional fetal hemoglobin (HbF) from normal hiPSC. 5,15 We now report for the first time in a normal and a pathological erythropoietic differentiation models that hiPSC are intrinsically able to mature into adult hemoglobin synthesizing cells.…”

Section: Introductionmentioning

confidence: 91%

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Human induced pluripotent stem cells can reach complete terminal maturation: in vivo and in vitro evidence in the erythropoietic differentiation model

et al. 2012

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The online version of this article has a Supplementary Appendix. BackgroundHuman induced pluripotent stem cells offer perspectives for cell therapy and research models for diseases. We applied this approach to the normal and pathological erythroid differentiation model by establishing induced pluripotent stem cells from normal and homozygous sickle cell disease donors. Design and MethodsWe addressed the question as to whether these cells can reach complete erythroid terminal maturation notably with a complete switch from fetal to adult hemoglobin. Sickle cell disease induced pluripotent stem cells were differentiated in vitro into red blood cells and characterized for their terminal maturation in terms of hemoglobin content, oxygen transport capacity, deformability, sickling and adherence. Nucleated erythroblast populations generated from normal and pathological induced pluripotent stem cells were then injected into non-obese diabetic severe combined immunodeficiency mice to follow the in vivo hemoglobin maturation. ResultsWe observed that in vitro erythroid differentiation results in predominance of fetal hemoglobin which rescues the functionality of red blood cells in the pathological model of sickle cell disease. We observed, in vivo, the switch from fetal to adult hemoglobin after infusion of nucleated erythroid precursors derived from either normal or pathological induced pluripotent stem cells into mice. ConclusionsThese results demonstrate that human induced pluripotent stem cells: i) can achieve complete terminal erythroid maturation, in vitro in terms of nucleus expulsion and in vivo in terms of hemoglobin maturation; and ii) open the way to generation of functionally corrected red blood cells from sickle cell disease induced pluripotent stem cells, without any genetic modification or drug treatment. ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

See 2 more Smart Citations

Human induced pluripotent stem cells can reach complete terminal maturation: in vivo and in vitro evidence in the erythropoietic differentiation model

et al. 2012

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“…In recent years, development of systems for the generation of erythrocytes in vitro have progressed rapidly using progenitor cells isolated from adult peripheral blood (PB), umbilical cord blood and human pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells (iPSC)). Progenitors isolated from cord blood have the distinct advantage of a greater proliferative capacity than those isolated from PB 1 whereas iPSC and immortalized erythroid progenitor cell lines derived from cord blood and iPSC 2,3 have the potential to provide an inexhaustible source of progenitors for the generation of large numbers of red blood cells (reviewed in Anstee et al, 4 Kaufman 5 and Peyrard et al 6 ). However, these progenitor cell sources express predominantly the β-like globins γ, or ε and γ, subunits of fetal (HbF) and embryonic (HbE) globin, in contrast to adult erythroid cells, which express β-globin.…”

Section: Introductionmentioning

confidence: 99%