Exploring the use of expanded erythroid cells for autologous transfusion for anemia of prematurity

Khodabux, C. M.; Hensbergen, Yvette van; Slot, Manon C.; Bakker-Verweij, Margreet; Giordano, Piero C.; Brand, Anneke

doi:10.1111/trf.12169

Cited by 4 publications

(4 citation statements)

References 33 publications

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“…The enucleation efficiency obtained by our culture was comparable to those by other groups with a co-culture-free system for erythrocyte differentiation starting from cord blood-derived progenitor cells [35–37]. In our study, filtration removed approximately 75% of cells, even though only 53% were nucleated.…”

Section: Discussionsupporting

confidence: 82%

Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model

et al. 2016

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Reliance on volunteer blood donors can lead to transfusion product shortages, and current liquid storage of red blood cells (RBCs) is associated with biochemical changes over time, known as ‘the storage lesion’. Thus, there is a need for alternative sources of transfusable RBCs to supplement conventional blood donations. Extracorporeal production of stem cell-derived RBCs (stemRBCs) is a potential and yet untapped source of fresh, transfusable RBCs. A number of groups have attempted RBC differentiation from CD34+ cells. However, it is still unclear whether these stemRBCs could eventually be effective substitutes for traditional RBCs due to potential differences in oxygen carrying capacity, viability, deformability, and other critical parameters. We have generated ex vivo stemRBCs from primary human cord blood CD34+ cells and compared them to donor-derived RBCs based on a number of in vitro parameters. In vivo, we assessed stemRBC circulation kinetics in an animal model of transfusion and oxygen delivery in a mouse model of exercise performance. Our novel, chronically anemic, SCID mouse model can evaluate the potential of stemRBCs to deliver oxygen to tissues (muscle) under resting and exercise-induced hypoxic conditions. Based on our data, stem cell-derived RBCs have a similar biochemical profile compared to donor-derived RBCs. While certain key differences remain between donor-derived RBCs and stemRBCs, the ability of stemRBCs to deliver oxygen in a living organism provides support for further development as a transfusion product.

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Section: Discussionsupporting

confidence: 82%

Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model

et al. 2016

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“…More recently, data have been published on the terminal differentiation of HSCs, which proved successful without a supportive cell layer. The expansion fold rate without a feeder layer was higher (~37 000) than with a feeder layer (~29 000), but the enucleation rates were ~68% and ~90%, respectively (Giarratana et al ., , ), while another study obtained a majority of erythroblasts and observed no reticuloctyes or erythrocytes after 21 days of culture (Khodabux et al ., ). The efficiency of enucleation is important in each of these cases, as is the effect this will have on the widespread potential of translating this redesigned culture into the clinic.…”

Section: The Stem Cell Environmentmentioning

confidence: 99%

Tissue engineering red blood cells: a therapeutic

Veen

Hunt

2014

J Tissue Eng Regen Med

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The use of red blood cells (RBCs) in transfusion is widespread in modern medicine. Limitations in blood transfusion have made an urgent argument for the focus on alternatives, as particular medical treatments heavily rely on the supply of donated blood. Stem cells have been successfully used in vitro to produce RBCs and researchers are currently challenged with developing larger-scale culture methods to meet the requirements for clinically relevant cell numbers. The ultimate conditions that will be beneficial for this type of research are trivial. A successful human clinical trial has shown that tremendous progress has already been made in this field. Other alternatives are based on the oxygen carrier protein that RBCs contain, i.e. haemoglobin (Hb). Chemically defined molecules and crosslinked proteins, which are able to bind and transport oxygen, have been found to be functional in vivo. Major progress has been achieved, but developing highly suitable products for the transfusion market still remains an enormous challenge for these acellular blood substitutes. We provide a review about developing alternatives for blood transfusion, with the emphasis on tissue-engineering approaches.

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“…Recent studies have elucidated the complex mechanisms underlying late-stage erythropoiesis by examining the in vitro generation of stem cell-derived red blood cells (RBCs). However, there are problems recapitulating this process in vitro, the main issues being delayed maturation, inefficient enucleation, low viability, dysregulated apoptosis, and dysplastic cell features, such as variable cell size and multi-nucleation [ 1 , 2 , 3 , 4 ]. These effects are thought to be due to the absence of certain stimulatory factors and signals, and to dysregulated autophagy.…”

Section: Introductionmentioning

confidence: 99%

Role of Plasma Gelsolin Protein in the Final Stage of Erythropoiesis and in Correction of Erythroid Dysplasia In Vitro

Han

Lee

Kim

et al. 2020

IJMS

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Gelsolin, an actin-remodeling protein, is involved in cell motility, cytoskeletal remodeling, and cytokinesis and is abnormally expressed in many cancers. Recently, human recombinant plasma gelsolin protein (pGSN) was reported to have important roles in cell cycle and maturation of primary erythroblasts. However, the role of human plasma gelsolin in late stage erythroblasts prior to enucleation and putative clinical relevance in patients with myelodysplastic syndrome (MDS) and hemato-oncologic diseases have not been reported. Polychromatic and orthochromatic erythroblasts differentiated from human cord blood CD34+ cells, and human bone marrow (BM) cells derived from patients with MDS, were cultured in serum-free medium containing pGSN. Effects of pGSN on mitochondria, erythroid dysplasia, and enucleation were assessed in cellular and transcriptional levels. With pGSN treatment, terminal maturation at the stage of poly- and ortho-chromatic erythroblasts was enhanced, with higher numbers of orthochromatic erythroblasts and enucleated red blood cells (RBCs). pGSN also significantly decreased dysplastic features of cell morphology. Moreover, we found that patients with MDS with multi-lineage dysplasia or with excess blasts-1 showed significantly decreased expression of gelsolin mRNA (GSN) in their peripheral blood. When BM erythroblasts of MDS patients were cultured with pGSN, levels of mRNA transcripts related to terminal erythropoiesis and enucleation were markedly increased, with significantly decreased erythroid dysplasia. Moreover, pGSN treatment enhanced mitochondrial transmembrane potential that is unregulated in MDS and cultured cells. Our findings demonstrate a key role for plasma gelsolin in erythropoiesis and in gelsolin-depleted MDS patients, and raises the possibility that pGSN administration may promote erythropoiesis in erythroid dysplasia.

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Exploring the use of expanded erythroid cells for autologous transfusion for anemia of prematurity

Cited by 4 publications

References 33 publications

Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model

Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model

Tissue engineering red blood cells: a therapeutic

Role of Plasma Gelsolin Protein in the Final Stage of Erythropoiesis and in Correction of Erythroid Dysplasia In Vitro

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