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Stem cell-derived erythrocytes as upcoming players in blood transfusion.

ABSTRACT: BACKGROUND:Blood transfusion is current standard-of-care for genetic forms of anemia that would be otherwise lethal and allows implementation of aggressive cytotoxic/surgical therapies developed for numerous types of cancer. In developed countries the blood supply is adequate and sporadically even in excess. However, difficulties exist in finding blood with rare phenotypes to treat alloimmunized patients and the progressive ageing of the human population predicts that blood will become scarce by 2050. These considerations establish the need for the development of techniques to generate cultured red blood cell (cRBCs) as transfusion products. MATERIALS AND METHODS:Recent progress in cell culture techniques is revolutionizing organ replacement therapies. Two new disciplines, cell therapy and tissue engineering, have been developed to generate in vitro therapeutic products for a variety of applications ranging from skin grafts to organ-function repairs. It is currently believed that these advances will eventually allow ex-vivo production of various cell types in numbers so great that, in the case of red cells, would be clinically adequate for transfusion. RESULTS:Proof-of-principle in animal models indicate that cRBCs generated from murine embryonic stem cells protect mice from lethal anemia. Conditions to generate small amounts of clinical grade cRBCs have been established and the first-in-man administration of autologous cRBCs perfomed. The results of this trial indicate that cRBCs survive in vivo at least as long as their natural counterpart. DISCUSSION:These ground-breaking reports have raised great excitement for clinical evaluation of cRBCs for transfusion. However, skepticism still persist that production of cRBCs in numbers sufficient for transfusion will ever be possible. This paper will discuss diagnostic and clinical goals pursuable with numbers of cRBCs that may be generated with current technology. CONCLUSION:We are confident that development of relevant clinical goals achievable with current technologies will not only improve clinical care in transfusion medicine but will also foster studies to overcome scientific and technical barriers that render transfusion with cRBCs of the general population impractical today.

SUBMITTER: Migliaccio AR

PROVIDER: S-EPMC4517842 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Stem cell-derived erythrocytes as upcoming players in blood transfusion.

Migliaccio A R AR

ISBT science series 20130601 1

<h4>Background</h4>Blood transfusion is current standard-of-care for genetic forms of anemia that would be otherwise lethal and allows implementation of aggressive cytotoxic/surgical therapies developed for numerous types of cancer. In developed countries the blood supply is adequate and sporadically even in excess. However, difficulties exist in finding blood with rare phenotypes to treat alloimmunized patients and the progressive ageing of the human population predicts that blood will become s ...[more]

PMID: 26229549

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Project description:ImportanceRed blood cell (RBC) transfusion is common among patients admitted to the intensive care unit (ICU). Despite multiple randomized clinical trials of hemoglobin (Hb) thresholds for transfusion, little is known about how these thresholds are incorporated into current practice.ObjectiveTo evaluate and describe ICU RBC transfusion practices worldwide.Design, setting, and participantsInternational, prospective, cohort study that involved 3643 adult patients from 233 ICUs in 30 countries on 6 continents from March 2019 to October 2022 with data collection in prespecified weeks.ExposureICU stay.Main outcomes and measuresThe primary outcome was the occurrence of RBC transfusion during ICU stay. Additional outcomes included the indication(s) for RBC transfusion (consisting of clinical reasons and physiological triggers), the stated Hb threshold and actual measured Hb values before and after an RBC transfusion, and the number of units transfused.ResultsAmong 3908 potentially eligible patients, 3643 were included across 233 ICUs (median of 11 patients per ICU [IQR, 5-20]) in 30 countries on 6 continents. Among the participants, the mean (SD) age was 61 (16) years, 62% were male (2267/3643), and the median Sequential Organ Failure Assessment score was 3.2 (IQR, 1.5-6.0). A total of 894 patients (25%) received 1 or more RBC transfusions during their ICU stay, with a median total of 2 units per patient (IQR, 1-4). The proportion of patients who received a transfusion ranged from 0% to 100% across centers, from 0% to 80% across countries, and from 19% to 45% across continents. Among the patients who received a transfusion, a total of 1727 RBC transfusions were administered, wherein the most common clinical indications were low Hb value (n = 1412 [81.8%]; mean [SD] lowest Hb before transfusion, 7.4 [1.2] g/dL), active bleeding (n = 479; 27.7%), and hemodynamic instability (n = 406 [23.5%]). Among the events with a stated physiological trigger, the most frequently stated triggers were hypotension (n = 728 [42.2%]), tachycardia (n = 474 [27.4%]), and increased lactate levels (n = 308 [17.8%]). The median lowest Hb level on days with an RBC transfusion ranged from 5.2 g/dL to 13.1 g/dL across centers, from 5.3 g/dL to 9.1 g/dL across countries, and from 7.2 g/dL to 8.7 g/dL across continents. Approximately 84% of ICUs administered transfusions to patients at a median Hb level greater than 7 g/dL.Conclusions and relevanceRBC transfusion was common in patients admitted to ICUs worldwide between 2019 and 2022, with high variability across centers in transfusion practices.

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Stem cell-derived erythrocytes as upcoming players in blood transfusion.

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Stem cell-derived erythrocytes as upcoming players in blood transfusion.

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