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Red blood cell production from immortalized progenitor cell line

  • Progress in Hematology
  • Seven wonders of erythropoiesis
  • Published:
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Abstract

The supply of transfusable red blood cells (RBCs) is not sufficient in many countries. If immortalized erythroid progenitor cell lines able to produce transfusable RBCs in vitro were established, they would be valuable resources. However, such cell lines have not been established. We have developed a robust method to establish immortalized erythroid progenitor cell lines following the induction of hematopoietic differentiation of mouse embryonic stem (ES) cells and have established many immortalized erythroid progenitor cell lines so far. Although their precise characteristics varied among cell lines, each of these lines could differentiate in vitro into more mature erythroid cells, including enucleated RBCs. Following transplantation of these erythroid cells into mice suffering from acute anemia, the cells proliferated transiently, subsequently differentiated into functional RBCs, and significantly ameliorated the acute anemia. Considering the number of human ES cell lines that have been established so far and the number of induced pluripotent stem cell lines that will be established in future, the intensive testing of a number of these lines for establishing immortalized erythroid progenitor cell lines may allow the establishment of such cell lines similar to the mouse erythroid progenitor cell lines.

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References

  1. Neildez-Nguyen TM, Wajcman H, Marden MC, Bensidhoum M, Moncollin V, Giarratana MC, Kobari L, Thierry D, Douay L. Human erythroid cells produced ex vivo at large scale differentiate into red blood cells in vivo. Nat Biotechnol. 2002;20:467–72.

    Article  CAS  PubMed  Google Scholar 

  2. Giarratana MC, Kobari L, Lapillonne H, Chalmers D, Kiger L, Cynober T, et al. Ex vivo generation of fully mature human red blood cells from hematopoietic stem cells. Nat Biotechnol. 2005;23:69–74.

    Article  CAS  PubMed  Google Scholar 

  3. Miharada K, Hiroyama T, Sudo K, Nagasawa T, Nakamura Y. Efficient enucleation of erythroblasts differentiated in vitro from hematopoietic stem and progenitor cells. Nat Biotechnol. 2006;24:1255–6.

    Article  CAS  PubMed  Google Scholar 

  4. Lee JC, Gimm JA, Lo AJ, Koury MJ, Krauss SW, Mohandas N, et al. Mechanism of protein sorting during erythroblast enucleation: role of cytoskeletal connectivity. Blood. 2004;103:1912–9.

    Article  CAS  PubMed  Google Scholar 

  5. Kingsley PD, Malik J, Fantauzzo KA, Palis J. Yolk sac-derived primitive erythroblasts enucleate during mammalian embryogenesis. Blood. 2004;104:19–25.

    Article  CAS  PubMed  Google Scholar 

  6. Ohneda O, Bautch VL. Murine endothelial cells support fetal liver erythropoiesis and myelopoiesis via distinct interactions. Brit J Haematol. 1997;98:798–808.

    Article  CAS  Google Scholar 

  7. Yanai N, Sato Y, Obinata M. A new type-II membrane protein in erythropoietic organs enhances erythropoiesis. Leukemia. 1997;11:484–5.

    PubMed  Google Scholar 

  8. Hanspal M, Smockova Y, Uong Q. Molecular identification and functional characterization of a novel protein that mediates the attachment of erythroblasts to macrophages. Blood. 1998;92:2940–50.

    CAS  PubMed  Google Scholar 

  9. Iavarone A, King ER, Dai XM, Leone G, Stanley ER, Lasorella A. Retinoblastoma promotes definitive erythropoiesis by repressing Id2 in fetal liver macrophages. Nature. 2004;432:1040–5.

    Article  CAS  PubMed  Google Scholar 

  10. Spike BT, Dirlam A, Dibling BC, Marvin J, Williams BO, Jacks T, et al. The Rb tumor suppressor is required for stress erythropoiesis. EMBO J. 2004;23:4319–29.

    Article  CAS  PubMed  Google Scholar 

  11. Yoshida H, Kawane K, Koike M, Mori Y, Uchiyama Y, Nagata S. Phosphatidylserine-dependent engulfment by macrophages of nuclei from erythroid precursor cells. Nature. 2005;437:754–8.

    Article  CAS  PubMed  Google Scholar 

  12. Hebiguchi M, Hirokawa M, Guo YM, Saito K, Wakui H, Komatsuda A, et al. Dynamics of human erythroblast enucleation. Int J Hematol. 2008;88:498–507.

    Article  PubMed  Google Scholar 

  13. Keller G, Kennedy M, Papayannopoulou T, Wiles MV. Hematopoietic commitment during embryonic stem cell differentiation in culture. Mol Cell Biol. 1993;13:473–86.

    CAS  PubMed  Google Scholar 

  14. Nakano T, Kodama H, Honjo T. Generation of lymphohematopoietic cells from embryonic stem cells in culture. Science. 1994;265:1098–101.

    Article  CAS  PubMed  Google Scholar 

  15. Nakano T, Kodama H, Honjo T. In vitro development of primitive and definitive erythrocytes from different precursors. Science. 1996;272:722–4.

    Article  CAS  PubMed  Google Scholar 

  16. Carotta S, Pilat S, Mairhofer A, Schmidt U, Dolznig H, Steinlein P, et al. Directed differentiation and mass cultivation of pure erythroid progenitors from mouse embryonic stem cells. Blood. 2004;104:1873–80.

    Article  CAS  PubMed  Google Scholar 

  17. Li F, Lu S, Vida L, Thomson JA, Honig GR. Bone morphogenetic protein 4 induces efficient hematopoietic differentiation of rhesus monkey embryonic stem cells in vitro. Blood. 2001;98:335–42.

    Article  CAS  PubMed  Google Scholar 

  18. Umeda K, Heike T, Yoshimoto M, Shiota M, Suemori H, Luo HY, et al. Development of primitive and definitive hematopoiesis from nonhuman primate embryonic stem cells in vitro. Development. 2004;131:1869–79.

    Article  CAS  PubMed  Google Scholar 

  19. Kurita R, Sasaki E, Yokoo T, Hiroyama T, Takasugi K, Imoto H, et al. Tal1/Scl gene transduction using a lentiviral vector stimulates highly efficient hematopoietic cell differentiation from common marmoset (Callithrix jacchus) embryonic stem cells. Stem Cells. 2006;24:2014–22.

    Article  CAS  PubMed  Google Scholar 

  20. Kaufman DS, Hanson ET, Lewis RL, Auerbach R, Thomson JA. Hematopoietic colony-forming cells derived from human embryonic stem cells. Proc Natl Acad Sci USA. 2001;98:10716–21.

    Article  CAS  PubMed  Google Scholar 

  21. Chadwick K, Wang L, Li L, Menendez P, Murdoch B, Rouleau A, et al. Cytokines and BMP-4 promote hematopoietic differentiation of human embryonic stem cells. Blood. 2003;102:906–15.

    Article  CAS  PubMed  Google Scholar 

  22. Cerdan C, Rouleau A, Bhatia M. VEGF-A165 augments erythropoietic development from human embryonic stem cells. Blood. 2004;103:2504–12.

    Article  CAS  PubMed  Google Scholar 

  23. Vodyanik MA, Bork JA, Thomson JA, Slukvin II. Human embryonic stem cell-derived CD34+ cells: efficient production in the coculture with OP9 stromal cells and analysis of lymphohematopoietic potential. Blood. 2005;105:617–26.

    Article  CAS  PubMed  Google Scholar 

  24. Wang L, Li L, Menendez P, Cerdan C, Bhatia M. Human embryonic stem cells maintained in the absence of mouse embryonic fibroblasts or conditioned media are capable of hematopoietic development. Blood. 2005;105:4598–603.

    Article  CAS  PubMed  Google Scholar 

  25. Olivier EN, Qiu C, Velho M, Hirsch RE, Bouhassira EE. Large-scale production of embryonic red blood cells from human embryonic stem cells. Exp Hematol. 2006;34:1635–42.

    Article  CAS  PubMed  Google Scholar 

  26. Hiroyama T, Miharada K, Aoki N, Fujioka T, Sudo K, Danjo I, et al. Long lasting in vitro hematopoiesis derived from primate embryonic stem cells. Exp Hematol. 2006;34:760–9.

    Article  CAS  PubMed  Google Scholar 

  27. Lu SJ, Feng Q, Park JS, Vida L, Lee BS, Strausbauch M, et al. Biologic properties and enucleation of red blood cells from human embryonic stem cells. Blood. 2008;112:4475–84.

    Article  CAS  PubMed  Google Scholar 

  28. Lansdorp PM. Role of telomerase in hematopoietic stem cells. Ann NY Acad Sci. 2005;1044:220–7.

    Article  CAS  PubMed  Google Scholar 

  29. Hiroyama T, Miharada K, Sudo K, Danjo I, Aoki N, Nakamura Y. Establishment of mouse embryonic stem cell-derived erythroid progenitor cell lines able to produce functional red blood cells. PLoS One. 2008;3:e1544.

    Google Scholar 

  30. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861–72.

    Article  CAS  PubMed  Google Scholar 

  31. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–76.

    Article  CAS  PubMed  Google Scholar 

  32. Fujioka T, Shimizu N, Yoshino K, Miyoshi H, Nakamura Y. Establishment of induced pluripotent stem cells from human neonatal tissues. Hum Cell. 2010;23:113–8.

    Article  PubMed  Google Scholar 

  33. Vogel G. Ready or not? Human ES cells head toward the clinic. Science. 2005;308:1534–8.

    Article  CAS  PubMed  Google Scholar 

  34. Hentze H, Graichen R, Colman A. Cell therapy and the safety of embryonic stem cell-derived grafts. Trends Biotechnol. 2007;25:24–32.

    Article  CAS  PubMed  Google Scholar 

  35. Schuldiner M, Itskovitz-Eldor J, Benvenisty N. Selective ablation of human embryonic stem cells expressing a “suicide” gene. Stem Cells. 2003;21:257–65.

    Article  CAS  PubMed  Google Scholar 

  36. Drukker M, Benvenisty N. The immunogenicity of human embryonic stem-derived cells. Trends Biotechnol. 2004;22:136–41.

    Article  CAS  PubMed  Google Scholar 

  37. Boyd AS, Higashi Y, Wood KJ. Transplanting stem cells: potential targets for immune attack. Modulating the immune response against embryonic stem cell transplantation. Adv Drug Deliv Rev. 2005;57:1944–69.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology in Japan.

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Authors and Affiliations

  1. Cell Engineering Division, RIKEN BioResource Center, Koyadai 3-1-1, Tsukuba, Ibaraki, 305-0074, Japan

    Yukio Nakamura, Takashi Hiroyama, Kenichi Miharada & Ryo Kurita

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  1. Yukio Nakamura
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  2. Takashi Hiroyama
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  3. Kenichi Miharada
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  4. Ryo Kurita
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Correspondence to Yukio Nakamura.

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Nakamura, Y., Hiroyama, T., Miharada, K. et al. Red blood cell production from immortalized progenitor cell line. Int J Hematol 93, 5–9 (2011). https://doi.org/10.1007/s12185-010-0742-2

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  • DOI: https://doi.org/10.1007/s12185-010-0742-2

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