An immortalized adult human erythroid line facilitates sustainable and scalable generation of functional red cells

Trakarnsanga, Kongtana; Griffiths, Rebecca E.; Wilson, Marieangela C.; Blair, Allison; Satchwell, Timothy J.; Meinders, Marjolein; Cogan, Nicola; Kupzig, Sabine; Kurita, Ryo; Nakamura, Yukio; Toye, Ashley M.; Anstee, David J.; Frayne, Jan

doi:10.1038/ncomms14750

Cited by 166 publications

(222 citation statements)

References 35 publications

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“…These epidemiological approaches will inform and contextualize laboratory studies of host-specificity at the cellular scale. Functional approaches will benefit from the recent generation of immortalized erythroid progenitor cell lines [74,75], which offer genetically tractable in vitro culture systems for the study of host-specificity. Finally, mathematical models of malaria zoonosis will be necessary to link transmission dynamics across these disparate scales of analysis.…”

Section: Discussionmentioning

confidence: 99%

Molecular interactions governing host-specificity of blood stage malaria parasites

Scully

Kanjee

Duraisingh

2017

Current Opinion in Microbiology

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Non-human primates harbor diverse species of malaria parasites, including the progenitors of P. falciparum and P. vivax. Cross-species transmission of some malaria parasites—most notably the macaque parasite, P. knowlesi—continues to this day, compelling the scientific community to ask whether these zoonoses could impede malaria control efforts by acting as a source of recurrent human infection. Host-restriction varies considerably among parasite species and is governed by both ecological and molecular variables. In particular, the efficiency of red blood cell invasion constitutes a prominent barrier to zoonotic emergence. Although proteins expressed upon the erythrocyte surface exhibit considerable diversity both within and among hosts, malaria parasites have adapted to this heterogeneity via the expansion of protein families associated with invasion, offering redundant mechanisms of host cell entry. This molecular toolkit may enable some parasites to circumvent host barriers, potentially yielding host shifts upon subsequent adaptation. Recent studies have begun to elucidate the molecular determinants of host-specificity, as well as the mechanisms that malaria parasites use to overcome these restrictions. We review recent studies concerning host tropism in the context of erythrocyte invasion by focusing on three malaria parasites that span the zoonotic spectrum: P. falciparum, P. knowlesi, and P. vivax.

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Section: Discussionmentioning

confidence: 99%

Molecular interactions governing host-specificity of blood stage malaria parasites

Scully

Kanjee

Duraisingh

2017

Current Opinion in Microbiology

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“…Huang et al adopted a mouse stromal cell (OP9) co‐culture system for terminal differentiation of IEs, yielding 30.8 ± 3.6% enucleated cells (CD235a + Draq5 − ) . Using a Tet‐inducible HPV16‐E6/E7 expression system, Trakarnsanga et al developed an immortalized line from early adult erythroblasts which were maintained proliferating in continuous culture for more than 6 months, maintaining their morphology and had a 30% enucleation efficiency . Hirata et al showed that the overexpression of c‐MYC in hematopoietic progenitor cells derived from hPSCs induces transient growth of the megakaryocyte‐erythrocyte progenitor population.…”

Section: Introductionmentioning

confidence: 99%

Defined Serum‐Free Medium for Bioreactor Culture of an Immortalized Human Erythroblast Cell Line

Lee

Lim

Chen

et al. 2018

Biotechnology Journal

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Anticipated shortages in donated blood supply have prompted investigation of alternative approaches for in vitro production of red blood cells (RBCs), such as expansion of conditional immortalization erythroid progenitors. However, there is a bioprocessing challenge wherein factors promoting maximal cell expansion and growth-limiting inhibitory factors are yet to be investigated. The authors use an erythroblast cell line (ImEry) derived from immortalizing CD71+CD235a+ erythroblast from adult peripheral blood for optimization of expansion culture conditions. Design of experiments (DOE) is used in media formulation to explore relationships and interactive effects between factors which affect cell expansion. Our in-house optimized medium formulation produced significantly higher cell densities (3.62 ± 0.055) × 10 cells mL , n = 3) compared to commercial formulations (2.07 ± 0.055) × 10 cells mL , n = 3; at 209 h culture). Culture media costs per unit of blood is shown to have a 2.96-3.09 times cost reduction. As a proof of principle for scale up, ImEry are expanded in a half-liter stirred-bioreactor under controlled settings. Growth characteristics, metabolic, and molecular profile of the cells are evaluated. ImEry has identical O binding capacity to adult erythroblasts. Amino acid supplementation results in further yield improvements. The study serves as a first step for scaling up erythroblast expansion in controlled bioreactors.

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“…These cells have only been studied in mice so far, but the results have been positive, and this may be a viable alternative to donor blood in the future (110). …”

Section: Blood Alternativesmentioning

confidence: 99%

Indications for and complications of transfusion and the management of gynecologic malignancies

Cybulska

Goss

Tew

et al. 2017

Gynecologic Oncology

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Anemia, which is highly prevalent in oncology patients, is one of the most established negative prognostic factors for several gynecologic malignancies. Multiple factors can cause or contribute to the development of anemia in patients with gynecologic cancers; these factors include blood loss (during surgery or directly from the tumor), renal impairment (caused by platinum-based chemotherapy), and marrow dysfunction (from metastases, chemotherapy, and/or radiation therapy). Several peri- and intra-operative strategies can be used to optimize patient management and minimize blood loss related to surgery. Blood transfusions are routinely employed as corrective measures against anemia; however, blood transfusions are one of the most overused healthcare interventions. There are safe and effective evidence-based blood transfusion strategies used in other patient populations that warrant further investigation in the surgical oncology setting. Blood is a valuable healthcare resource, and clinicians can learn to use it more judiciously through knowledge of the potential risks and complications of blood interventions, as well as the ability to properly identify the patients most likely to benefit from such interventions.

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An immortalized adult human erythroid line facilitates sustainable and scalable generation of functional red cells

Cited by 166 publications

References 35 publications

Molecular interactions governing host-specificity of blood stage malaria parasites

Molecular interactions governing host-specificity of blood stage malaria parasites

Defined Serum‐Free Medium for Bioreactor Culture of an Immortalized Human Erythroblast Cell Line

Indications for and complications of transfusion and the management of gynecologic malignancies

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