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Letter to the Editor

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Blood Res 2017; 52(4):

Published online December 31, 2017

https://doi.org/10.5045/br.2017.52.4.316

© The Korean Society of Hematology

Transplantation of human umbilical cord blood CD34+ cells into the liver of newborn NOD/SCID/IL-2Rγ null (NSG) mice after busulfan conditioning

Yunmi Ko1, Yeon Ho Jeong2, and Jun Ah Lee1,3*

Author Info. +

1Division of Clinical Translational Research, Korea Cancer Center Hospital, Seoul, Korea.

2Department of Medical Biotechnology, College of Biomedical Science, Kangwon National University, Chuncheon, Korea.

3Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Korea.

Correspondence to : Jun Ah Lee. Department of Pediatrics, Korea Cancer Center Hospital, 75 Nowon-ro, Nowon-gu, Seoul 01812, Korea. junahlee@kcch.re.kr

Received: February 3, 2017; Revised: April 5, 2017; Accepted: June 15, 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

FIGURES

Go to
Fig. 1.

Survival and weight changes of newborn NSG mice after hCD34+ cell injection. Humanized NSG mice were monitored daily from the 3rd week of transplantation. Most of the newborn NSG mice did well, but two showed features suggesting graft versus host disease (weight loss, hunched posture, and diminished activity) and died on the 26th day of transplantation.


Fig. 2.

Reconstitution of human cells in newborn NSG mice after intrahepatic transplantation of CD34+ cells. Mononuclear cells derived from bone marrow, spleen, peripheral blood and liver tissues of humanized NSG mice were isolated in the 12th week of transplantation and were stained with anti-hCD45, anti-hCD3, and anti-hCD19 antibodies. Data are means±SEM and representative of four mice per group, excluding lowest values (N=5).

Abbreviations: BM, bone marrow; LV, liver; ND, not detected; PB, peripheral blood; SPL, spleen.


REFERENCES

Go to
  1. Shultz, LD, Brehm, MA, Garcia-Martinez, JV, Greiner, DL. Humanized mice for immune system investigation: progress, promise and challenges. Nat Rev Immunol, 2012;12;786-798.
    Pubmed
  2. Palis, J, Robertson, S, Kennedy, M, Wall, C, Keller, G. Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. Development, 1999;126;5073-5084.
    Pubmed
  3. Sasaki, K, Iwatsuki, H. Origin and fate of the central macrophages of erythroblastic islands in the fetal and neonatal mouse liver. Microsc Res Tech, 1997;39;398-405.
    Pubmed
  4. Martin, MA, Bhatia, M. Analysis of the human fetal liver hematopoietic microenvironment. Stem Cells Dev, 2005;14;493-504.
    Pubmed
  5. Dalakas, E, Newsome, PN, Harrison, DJ, Plevris, JN. Hematopoietic stem cell trafficking in liver injury. FASEB J, 2005;19;1225-1231.
    Pubmed
  6. Wulf-Goldenberg, A, Keil, M, Fichtner, I, Eckert, K. Intrahepatic transplantation of CD34+ cord blood stem cells into newborn and adult NOD/SCID mice induce differential organ engraftment. Tissue Cell, 2012;44;80-86.
    Pubmed
  7. Navarro-Montero, O, Romero-Moya, D, Montes, R, et al. Intrahepatic transplantation of cord blood CD34+ cells into newborn NOD/SCID-IL2Rγ(null) mice allows efficient multi-organ and multi-lineage hematopoietic engraftment without accessory cells. Clin Immunol, 2012;145;89-91.
    Pubmed
  8. Choi, B, Chun, E, Kim, M, et al. Human T cell development in the liver of humanized NOD/SCID/IL-2Rγ(null)(NSG) mice generated by intrahepatic injection of CD34(+) human (h) cord blood (CB) cells. Clin Immunol, 2011;139;321-335.
    Pubmed
  9. Brehm, MA, Shultz, LD, Luban, J, Greiner, DL. Overcoming current limitations in humanized mouse research. J Infect Dis, 2013;208;S125-S130.
    Pubmed
  10. Ishikawa, F, Yasukawa, M, Lyons, B, et al. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice. Blood, 2005;106;1565-1573.
    Pubmed
  11. McKenzie, JL, Gan, OI, Doedens, M, Dick, JE. Human short-term repopulating stem cells are efficiently detected following intrafemoral transplantation into NOD/SCID recipients depleted of CD122+ cells. Blood, 2005;106;1259-1261.
    Pubmed
  12. Lavender, KJ, Messer, RJ, Race, B, Hasenkrug, KJ. Production of bone marrow, liver, thymus (BLT) humanized mice on the C57BL/6 Rag2(-/-)γc(-/-)CD47(-/-) background. J Immunol Methods, 2014;407;127-134.
    Pubmed
  13. van Lent, AU, Dontje, W, Nagasawa, M, et al. IL-7 enhances thymic human T cell development in “human immune system” Rag2-/-IL-2Rgammac-/- mice without affecting peripheral T cell homeostasis. J Immunol, 2009;183;7645-7655.
    Pubmed
  14. Chen, Q, Khoury, M, Chen, J. Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice. Proc Natl Acad Sci U S A, 2009;106;21783-21788.
    Pubmed
  15. Drake, AC, Chen, Q, Chen, J. Engineering humanized mice for improved hematopoietic reconstitution. Cell Mol Immunol, 2012;9;215-224.
    Pubmed

Article

Letter to the Editor

Blood Res 2017; 52(4): 316-319

Published online December 31, 2017 https://doi.org/10.5045/br.2017.52.4.316

Copyright © The Korean Society of Hematology.

Transplantation of human umbilical cord blood CD34+ cells into the liver of newborn NOD/SCID/IL-2Rγ null (NSG) mice after busulfan conditioning

Yunmi Ko1, Yeon Ho Jeong2, and Jun Ah Lee1,3*

1Division of Clinical Translational Research, Korea Cancer Center Hospital, Seoul, Korea.

2Department of Medical Biotechnology, College of Biomedical Science, Kangwon National University, Chuncheon, Korea.

3Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Korea.

Correspondence to:Jun Ah Lee. Department of Pediatrics, Korea Cancer Center Hospital, 75 Nowon-ro, Nowon-gu, Seoul 01812, Korea. junahlee@kcch.re.kr

Received: February 3, 2017; Revised: April 5, 2017; Accepted: June 15, 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Fig 1.

    Download
    Figure 1.

    Survival and weight changes of newborn NSG mice after hCD34+ cell injection. Humanized NSG mice were monitored daily from the 3rd week of transplantation. Most of the newborn NSG mice did well, but two showed features suggesting graft versus host disease (weight loss, hunched posture, and diminished activity) and died on the 26th day of transplantation.

    Blood Research 2017; 52: 316-319https://doi.org/10.5045/br.2017.52.4.316

    Fig 2.

    Download
    Figure 2.

    Reconstitution of human cells in newborn NSG mice after intrahepatic transplantation of CD34+ cells. Mononuclear cells derived from bone marrow, spleen, peripheral blood and liver tissues of humanized NSG mice were isolated in the 12th week of transplantation and were stained with anti-hCD45, anti-hCD3, and anti-hCD19 antibodies. Data are means±SEM and representative of four mice per group, excluding lowest values (N=5).

    Abbreviations: BM, bone marrow; LV, liver; ND, not detected; PB, peripheral blood; SPL, spleen.

    Blood Research 2017; 52: 316-319https://doi.org/10.5045/br.2017.52.4.316

    References

    1. Shultz, LD, Brehm, MA, Garcia-Martinez, JV, Greiner, DL. Humanized mice for immune system investigation: progress, promise and challenges. Nat Rev Immunol, 2012;12;786-798.
      Pubmed
    2. Palis, J, Robertson, S, Kennedy, M, Wall, C, Keller, G. Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. Development, 1999;126;5073-5084.
      Pubmed
    3. Sasaki, K, Iwatsuki, H. Origin and fate of the central macrophages of erythroblastic islands in the fetal and neonatal mouse liver. Microsc Res Tech, 1997;39;398-405.
      Pubmed
    4. Martin, MA, Bhatia, M. Analysis of the human fetal liver hematopoietic microenvironment. Stem Cells Dev, 2005;14;493-504.
      Pubmed
    5. Dalakas, E, Newsome, PN, Harrison, DJ, Plevris, JN. Hematopoietic stem cell trafficking in liver injury. FASEB J, 2005;19;1225-1231.
      Pubmed
    6. Wulf-Goldenberg, A, Keil, M, Fichtner, I, Eckert, K. Intrahepatic transplantation of CD34+ cord blood stem cells into newborn and adult NOD/SCID mice induce differential organ engraftment. Tissue Cell, 2012;44;80-86.
      Pubmed
    7. Navarro-Montero, O, Romero-Moya, D, Montes, R, et al. Intrahepatic transplantation of cord blood CD34+ cells into newborn NOD/SCID-IL2Rγ(null) mice allows efficient multi-organ and multi-lineage hematopoietic engraftment without accessory cells. Clin Immunol, 2012;145;89-91.
      Pubmed
    8. Choi, B, Chun, E, Kim, M, et al. Human T cell development in the liver of humanized NOD/SCID/IL-2Rγ(null)(NSG) mice generated by intrahepatic injection of CD34(+) human (h) cord blood (CB) cells. Clin Immunol, 2011;139;321-335.
      Pubmed
    9. Brehm, MA, Shultz, LD, Luban, J, Greiner, DL. Overcoming current limitations in humanized mouse research. J Infect Dis, 2013;208;S125-S130.
      Pubmed
    10. Ishikawa, F, Yasukawa, M, Lyons, B, et al. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice. Blood, 2005;106;1565-1573.
      Pubmed
    11. McKenzie, JL, Gan, OI, Doedens, M, Dick, JE. Human short-term repopulating stem cells are efficiently detected following intrafemoral transplantation into NOD/SCID recipients depleted of CD122+ cells. Blood, 2005;106;1259-1261.
      Pubmed
    12. Lavender, KJ, Messer, RJ, Race, B, Hasenkrug, KJ. Production of bone marrow, liver, thymus (BLT) humanized mice on the C57BL/6 Rag2(-/-)γc(-/-)CD47(-/-) background. J Immunol Methods, 2014;407;127-134.
      Pubmed
    13. van Lent, AU, Dontje, W, Nagasawa, M, et al. IL-7 enhances thymic human T cell development in “human immune system” Rag2-/-IL-2Rgammac-/- mice without affecting peripheral T cell homeostasis. J Immunol, 2009;183;7645-7655.
      Pubmed
    14. Chen, Q, Khoury, M, Chen, J. Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice. Proc Natl Acad Sci U S A, 2009;106;21783-21788.
      Pubmed
    15. Drake, AC, Chen, Q, Chen, J. Engineering humanized mice for improved hematopoietic reconstitution. Cell Mol Immunol, 2012;9;215-224.
      Pubmed
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