Email Alert RSS
Volume 15 Issue 1
Jan.  2024
Turn off MathJax
Article Contents
Abstract
References
Related Articles
WANG Hui, ZHANG Jinjin, CHEN Lili, XING Yanchao. In Vitro Production of Red Blood Cells: Progress and Challenge[J]. Medical Journal of Peking Union Medical College Hospital, 2024, 15(1): 166-171. DOI: 10.12290/xhyxzz.2023-0299
Citation: WANG Hui, ZHANG Jinjin, CHEN Lili, XING Yanchao. In Vitro Production of Red Blood Cells: Progress and Challenge[J]. Medical Journal of Peking Union Medical College Hospital, 2024, 15(1): 166-171. DOI: 10.12290/xhyxzz.2023-0299
shu

In Vitro Production of Red Blood Cells: Progress and Challenge

  • 1.

    School of Postgraduates, Xinjiang Medical University, Urumqi 830054, China

  • 2.

    Department of Transfusion Medicine, General Hospital of Xinjiang Military Command, Urumqi 830000, China

Funds: 

Natural Science Foundation of Xinjiang Uygur Autonomous Region 2022D01C342

More Information
  • Corresponding author:

    XING Yanchao, E-mail: xingyanchao@aliyun.com

  • Received Date: June 17, 2023
  • Accepted Date: July 30, 2023
  • Issue Publish Date: January 29, 2024
    Graphical Abstract
    • Abstract
  • Although blood protection technologies such as autologous blood transfusion can alleviate to some extent the short supply of clinical blood, red blood cells are still in great demand as the main blood component. This problem can be solved by the safe production of red blood cells in vitro. At present, mature erythrocytes can be differentiated from embryonic stem cells, human induced pluripotent stem cells, umbilical cord blood, peripheral blood, and immortalized erythroid progenitor cell lines. This article reviews the sources and applications of red blood cells produced in vitro, and analyzes the current challenges, in order to provide new insights for blood transfusion therapy.
    • FullText(HTML)
    • References (46)
  • [1]
    中华人民共和国国家卫生健康委员会规划发展与信息化司. 2021年我国卫生健康事业发展统计公报[EB/OL]. (2022-07-12)[2023-06-18]. http://www.nhc.gov.cn/guihuaxxs/s3586s/202207/51b55216c2154332a660157abf28b09d.shtml.

    Planning, Development and Informatization Department of the National Health Commission of the People's Republic of China. Statistical bulletin on the development of health care in China in 2021[EB/OL]. (2022-07-12)[2023-06-18]. http://www.nhc.gov.cn/guihuaxxs/s3586s/202207/51b55216c2154332a660157abf28b09d.shtml.
    [2]
    Franchini M, Forni G L, Marano G, et al. Red blood cell alloimmunisation in transfusion-dependent thalassaemia: a systematic review[J]. Blood Transfus, 2019, 17(1): 4-15.
    [3]
    Jahr J S, Guinn N R, Lowery D R, et al. Blood substitutes and oxygen therapeutics: a review[J]. Anesth Analg, 2021, 132(1): 119-129. DOI: 10.1213/ANE.0000000000003957
    [4]
    Bernecker C, Matzhold E M, Kolb D, et al. Membrane properties of human induced pluripotent stem cell-derived cultured red blood cells[J]. Cells, 2022, 11(16): 2473. DOI: 10.3390/cells11162473
    [5]
    Wang S H, Zhao H Z, Zhang H, et al. Analyses of erythropoiesis from embryonic stem cell-CD34+ and cord blood-CD34+ cells reveal mechanisms for defective expansion and enucleation of embryomic stem cell-erythroid cells[J]. J Cell Mol Med, 2022, 26(8): 2404-2416. DOI: 10.1111/jcmm.17263
    [6]
    Bernecker C, Ackermann M, Lachmann N, et al. Enhanced ex vivo generation of erythroid cells from human induced pluripotent stem cells in a simplified cell culture system with low cytokine support[J]. Stem Cells Dev, 2019, 28(23): 1540-1551. DOI: 10.1089/scd.2019.0132
    [7]
    Rallapalli S, Guhathakurta S, Narayan S, et al. Generation of clinical-grade red blood cells from human umbilical cord blood mononuclear cells[J]. Cell Tissue Res, 2019, 375(2): 437-449. DOI: 10.1007/s00441-018-2919-6
    [8]
    Liu S Q, Wu M Y, Lancelot M, et al. BMI1 enables extensive expansion of functional erythroblasts from human peripheral blood mononuclear cells[J]. Mol Ther, 2021, 29(5): 1918-1932. DOI: 10.1016/j.ymthe.2021.01.022
    [9]
    Daniels D E, Ferguson D C J, Griffiths R E, et al. Reproducible immortalization of erythroblasts from multiple stem cell sources provides approach for sustainable RBC therapeutics[J]. Mol Ther Methods Clin Dev, 2021, 22: 26-39. DOI: 10.1016/j.omtm.2021.06.002
    [10]
    Ackermann M, Liebhaber S, Klusmann J H, et al. Lost in translation: pluripotent stem cell-derived hematopoiesis[J]. EMBO Mol Med, 2015, 7(11): 1388-1402. DOI: 10.15252/emmm.201505301
    [11]
    Di Buduo C A, Aguilar A, Soprano P M, et al. Latest culture techniques: cracking the secrets of bone marrow to mass-produce erythrocytes and platelets ex vivo[J]. Haematologica, 2021, 106(4): 947-957.
    [12]
    Sun S M, Peng Y L, Liu J. Research advances in erythrocyte regeneration sources and methods in vitro[J]. Cell Regen, 2018, 7(2): 45-49. DOI: 10.1016/j.cr.2018.10.001
    [13]
    Seo Y, Shin K H, Kim H H, et al. Current advances in red blood cell generation using stem cells from diverse sources[J]. Stem Cells Int, 2019, 2019: 9281329.
    [14]
    Focosi D, Pistello M. Effect of induced pluripotent stem cell technology in blood banking[J]. Stem Cells Transl Med, 2016, 5(3): 269-274. DOI: 10.5966/sctm.2015-0257
    [15]
    Hansen M, Von Lindern M, Van Den Akker E, et al. Human-induced pluripotent stem cell-derived blood products: state of the art and future directions[J]. FEBS Lett, 2019, 593(23): 3288-3303. DOI: 10.1002/1873-3468.13599
    [16]
    Trakarnsanga K, Ferguson D, Daniels D E, et al. Vimentin expression is retained in erythroid cells differentiated from human iPSC and ESC and indicates dysregulation in these cells early in differentiation[J]. Stem Cell Res Ther, 2019, 10(1): 130. DOI: 10.1186/s13287-019-1231-z
    [17]
    Zhang Y, Wang C, Wang L, et al. Large-scale ex vivo generation of human red blood cells from cord blood CD34+ cells[J]. Stem Cells Transl Med, 2017, 6(8): 1698-1709. DOI: 10.1002/sctm.17-0057
    [18]
    Xie X Y, Yao H L, Han X Y, et al. Therapeutic use of red blood cells and platelets derived from human cord blood stem cells[J]. Stem Cells Transl Med, 2021, 10(Suppl 2): S48-S53.
    [19]
    Heshusius S, Heideveld E, Burger P, et al. Large-scale in vitro production of red blood cells from human peripheral blood mononuclear cells[J]. Blood Adv, 2019, 3(21): 3337-3350. DOI: 10.1182/bloodadvances.2019000689
    [20]
    Cervellera C F, Mazziotta C, Di Mauro G, et al. Immorta-lized erythroid cells as a novel frontier for in vitro blood production: current approaches and potential clinical application[J]. Stem Cell Res Ther, 2023, 14(1): 139. DOI: 10.1186/s13287-023-03367-8
    [21]
    Kurita R, Suda N, Sudo K, et al. Establishment of immortalized human erythroid progenitor cell lines able to produce enucleated red blood cells[J]. PLoS One, 2013, 8(3): e59890. DOI: 10.1371/journal.pone.0059890
    [22]
    Trakarnsanga K, Griffiths R E, Wilson M C, et al. An immortalized adult human erythroid line facilitates sustainable and scalable generation of functional red cells[J]. Nat Commun, 2017, 8: 14750. DOI: 10.1038/ncomms14750
    [23]
    Daniels D E, Downes D J, Ferrer-Vicens I, et al. Comparing the two leading erythroid lines BEL-A and HUDEP-2[J]. Haematologica, 2020, 105(8): e389-e394. DOI: 10.3324/haematol.2019.229211
    [24]
    Bagchi A, Nath A, Thamodaran V, et al. Direct generation of immortalized erythroid progenitor cell lines from peripheral blood mononuclear cells[J]. Cells, 2021, 10(3): 523. DOI: 10.3390/cells10030523
    [25]
    Soboleva S, Kurita R, Kajitani N, et al. Establishment of an immortalized human erythroid cell line sustaining differentiation potential without inducible gene expression system[J]. Hum Cell, 2022, 35(1): 408-417. DOI: 10.1007/s13577-021-00652-7
    [26]
    Mujahid A, Dickert F L. Blood group typing: from classical strategies to the application of synthetic antibodies generated by molecular imprinting[J]. Sensors (Basel), 2015, 16(1): 51. DOI: 10.3390/s16010051
    [27]
    Kupzig S, Parsons S F, Curnow E, et al. Superior survival of ex vivo cultured human reticulocytes following transfusion into mice[J]. Haematologica, 2017, 102(3): 476-483. DOI: 10.3324/haematol.2016.154443
    [28]
    Trakarnsanga K, Tipgomut C, Metheetrairut C, et al. Generation of an immortalised erythroid cell line from haematopoietic stem cells of a haemoglobin E/β-thalassemia patient[J]. Sci Rep, 2020, 10(1): 16798. DOI: 10.1038/s41598-020-73991-4
    [29]
    Satchwell T J, Wright K E, Haydn-Smith K L, et al. Genetic manipulation of cell line derived reticulocytes enables dissection of host malaria invasion requirements[J]. Nat Commun, 2019, 10(1): 3806. DOI: 10.1038/s41467-019-11790-w
    [30]
    Satchwell T J. Generation of red blood cells from stem cells: achievements, opportunities and perspectives for malaria research[J]. Front Cell Infect Microbiol, 2022, 12: 1039520. DOI: 10.3389/fcimb.2022.1039520
    [31]
    Jiang Y, Yuan Y, Peng F, et al. Erythrocyte-based drug delivery: how far from clinical application?[J]. Curr Drug Deliv, 2024, 21(1): 52-64. DOI: 10.2174/1567201820666230320103529
    [32]
    Zhang G S, Huang X F, Xiu H Q, et al. Extracellular vesicles: natural liver-accumulating drug delivery vehicles for the treatment of liver diseases[J]. J Extracell Vesicles, 2020, 10(2): e12030. DOI: 10.1002/jev2.12030
    [33]
    Thangaraju K, Neerukonda S N, Katneni U, et al. Extracellular vesicles from red blood cells and their evolving roles in health, coagulopathy and therapy[J]. Int J Mol Sci, 2020, 22(1): 153. DOI: 10.3390/ijms22010153
    [34]
    Izzati Mat Rani N N, Alzubaidi Z M, Azhari H, et al. Novel engineering: biomimicking erythrocyte as a revolutionary platform for drugs and vaccines delivery[J]. Eur J Pharmacol, 2021, 900: 174009. DOI: 10.1016/j.ejphar.2021.174009
    [35]
    Li W S, Su Z G, Hao M X, et al. Cytopharmaceuticals: an emerging paradigm for drug delivery[J]. J Control Release, 2020, 328: 313-324. DOI: 10.1016/j.jconrel.2020.08.063
    [36]
    Yang L, Huang S Q, Zhang Z R, et al. Roles and applications of red blood cell-derived extracellular vesicles in health and diseases[J]. Int J Mol Sci, 2022, 23(11): 5927. DOI: 10.3390/ijms23115927
    [37]
    Kweon S, Kim S, Baek E J. Current status of red blood cell manufacturing in 3D culture and bioreactors[J]. Blood Res, 2023, 58(S1): S46-S51. DOI: 10.5045/br.2023.2023008
    [38]
    Mei Y, Liu Y J, Ji P. Understanding terminal erythro-poiesis: an update on chromatin condensation, enucleation, and reticulocyte maturation[J]. Blood Rev, 2021, 46: 100740. DOI: 10.1016/j.blre.2020.100740
    [39]
    Soboleva S, Miharada K. Induction of enucleation in primary and immortalized erythroid cells[J]. Int J Hematol, 2022, 116(2): 192-198. DOI: 10.1007/s12185-022-03386-w
    [40]
    Zhang R R, Zhu X F. Relationship between macrophages and erythropoiesis[J]. Chin J Contemp Pediatr, 2016, 18(1): 94-99.
    [41]
    Sivalingam J, SuE Y, Lim Z R, et al. A scalable suspension platform for generating high-density cultures of universal red blood cells from human induced pluripotent stem cells[J]. Stem Cell Reports, 2021, 16(1): 182-197. DOI: 10.1016/j.stemcr.2020.11.008
    [42]
    Pellegrin S, Severn C E, Toye A M. Towards manufactured red blood cells for the treatment of inherited anemia[J]. Haematologica, 2021, 106(9): 2304-2311.
    [43]
    Seghatchian J, Amiral J. Spotlight on the current perspectives on applications of human blood cell culture and organoids: Introductory remarks[J]. Transfus Apher Sci, 2020, 59(4): 102861.
    [44]
    Gallego-Murillo J S, Iacono G, Van Der Wielen L A M, et al. Expansion and differentiation of ex vivo cultured erythroblasts in scalable stirred bioreactors[J]. Biotechnol Bioeng, 2022, 119(11): 3096-3116.
    [45]
    Giarratana M C, Rouard H, Dumont A, et al. Proof of principle for transfusion of in vitro-generated red blood cells[J]. Blood, 2011, 118(19): 5071-5079.
    [46]
    National Health Service. First ever clinical trial of laboratory grown red blood cells being transfused into another person[EB/OL]. (2022-11-07)[2023-06-18]. https://www.nhsbt.nhs.uk/news/first-ever-clinical-trial-of-labora-tory-grown-red-blood-cells-being-transfused-into-another-person/.
    • Related Articles

  • Related Articles

    [1]WANG Haiying, ZHANG Jinjin, SUN Xiaoli, XING Yanchao. Risk of Circulating Tumor Cells and Clinical Blood Transfusion[J]. Medical Journal of Peking Union Medical College Hospital. DOI: 10.12290/xhyxzz.2024-0493
    [2]XIAO Nan, LI Zhanfeng, YAO Jianxin, PAN Zhiyao, YAO Zhifeng. Long Non-coding RNA and Cancer Stem Cells[J]. Medical Journal of Peking Union Medical College Hospital, 2021, 12(3): 373-379. DOI: 10.12290/xhyxzz.20190231
    [3]TANG Bo, XU Xiaohan, ZHANG Yuelun, HUANG Yuguang. A Longitudinal Study of Perioperative Allogeneic Red Blood Cell Transfusion among Patients Undergoing Thoracotomy for Lobectomy in China[J]. Medical Journal of Peking Union Medical College Hospital, 2021, 12(3): 333-338. DOI: 10.12290/xhyxzz.2021-0140
    [4]Shu-bin WU, Wei-yun CHEN, Yu-guang HUANG. Non-antibody Mediated Transfusion Related Acute Lung Injury[J]. Medical Journal of Peking Union Medical College Hospital, 2017, 8(4-5): 294-299. DOI: 10.3969/j.issn.1674-9081.2017.05.019
    [5]Xiao-feng LI, Chao-ji ZHANG, Jian-zhou LIU, Guo-tao MA, Xing-rong LIU, Qi MIAO. Correlation Between Blood Transfusion and Postoperative Outcomes following Cardiac Surgery: A Systematic Review[J]. Medical Journal of Peking Union Medical College Hospital, 2016, 7(6): 426-431. DOI: 10.3969/j.issn.1674-9081.2016.06.005
    [6]Jia-yuan DAI, Sheng-yong XU, Jun XU, Ye-cheng LIU, Ji-hai LIU, Hua-dong ZHU, Xue-zhong YU. Current Situation and Strategy of Blood Transfusion in Emergency Department of Peking Union Medical College Hospital[J]. Medical Journal of Peking Union Medical College Hospital, 2016, 7(5): 384-387. DOI: 10.3969/j.issn.1674-9081.2016.05.012
    [7]Yi ZHAO, Jin LIN, Han-zhong LI, Yuan-xiang FANG, Shuang WANG. Blood Use in Surgical Patients with Red Blood Cell Transfusion of Over 20 Units during Single Hospital Stay[J]. Medical Journal of Peking Union Medical College Hospital, 2016, 7(5): 367-370. DOI: 10.3969/j.issn.1674-9081.2016.05.009
    [8]Tao WANG, Jin-song GAO, Keng SHEN, Ling-ya PAN, Yang XIANG, Lan ZHU. Current Status and Characteristics of Perioperative Transfusion in Gynecologic Patients[J]. Medical Journal of Peking Union Medical College Hospital, 2015, 6(5): 357-360. DOI: 10.3969/j.issn.1674-9081.2015.05.009
    [9]Yi-feng ZHONG, Jian-qiu YANG, Tao WANG, Jing HU, Jun-tao LIU, Jin-song GAO. Retrospective Analysis for Causes of Perinatal Blood Transfusion[J]. Medical Journal of Peking Union Medical College Hospital, 2015, 6(4): 296-299. DOI: 10.3969/j.issn.1674-9081.2015.04.013
    [10]Xiao-hua SHI, Zhi-yong LIANG, Huan-wen WU, Xin-yu REN, Tong-hua LIU. Effect of RNA Interference Plasmid on the Expression of Oncogene AKT2 in Pancreatic Cancer Cell Line Panc-1[J]. Medical Journal of Peking Union Medical College Hospital, 2012, 3(1): 102-108. DOI: 10.3969/j.issn.1674-9081.2012.01.021

Catalog

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (435) PDF downloads (50) Cited by()
    Related
    Links: National Health Commission of the People's Republic of China Chinese Academy of Medical Sciences(CAMS) AMLC Check CNKI Database CNKI Term Online Chinese General Practice
    Address：Room 302,Third Floor,Building 7, No. 1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing 100730, China
    Tel：010-69154261/4262
    E - mail：medj@pumch.cn mjpumch@126.com
    Copyright of website：Editorial Office of Medical Journal of Peking Union Medical College Hospital

    Supported by: Beijing Renhe Information Technology Co., Ltd.  Baidu Analytics

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return
    x Close Forever Close