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Stem Cells

In vivo dynamics of human cord blood-derived CD34− SCID-repopulating cells using intra-bone marrow injection

Leukemia volume 24, pages 162–168 (2010)Cite this article

Abstract

The identification of human CD34-negative (CD34−) hematopoietic stem cells (HSCs) provides a new concept for the hierarchy in the human HSC compartment. This study investigated the long-term repopulating capacity and redistribution kinetics of human cord blood-derived CD34− severe combined immunodeficiency (SCID)-repopulating cells (SRCs) and compared them with those of CD34+CD38+ and CD34+CD38− SRCs using the intra-bone marrow injection (IBMI) to clarify the characteristics of CD34− SRCs. On the basis of the limiting dilution analyses data, estimated numbers of CD34+CD38+, CD34+CD38−, and CD34− SRCs were transplanted to NOD/SCID mice by IBMI. The human cell repopulation at the site of injection and the other bones were serially investigated. Interestingly, CD34+CD38+, CD34+CD38−, and CD34− SRCs began to migrate to other bones 2 and 5 weeks after the transplantation, respectively. Accordingly, the initiation of migration seemed to differ between the CD34+ and CD34− SRCs. In addition, CD34+CD38+ SRCs only sustained a short-term repopulation. However, both CD34+CD38− and CD34− SRCs had longer-term repopulation capacity. Taken together, these findings showed that CD34− SRCs show different in vivo kinetics, thus suggesting that the identified CD34− SRCs are a distinct class of primitive HSCs in comparison to the CD34+CD38+ and CD34+CD38− SRCs.

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Acknowledgements

This work was supported by Grants-in-Aid for Scientific Research C (grant Nos. 19591144 and 21591251) from the Ministry of Education, Science and Culture of Japan, a grant from Haiteku Research Center of the Ministry of Education, a grant from the Science Frontier Program of the Ministry of Education, a grant from the 21st Century Center of Excellence (COE) program of the Ministry of Education, a grant from the Promotion and Mutual Aid Corporation for Private Schools of Japan, a grant from Kansai Medical University (Research grant B), a grant from the Japan Leukemia Research Foundation, a grant from the Mitsubishi Pharma Research Foundation, and a grant from the Takeda Science Foundation.

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Authors and Affiliations

  1. Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, Moriguchi, Osaka, Japan

    T Kimura, Y Matsuoka, M Murakami, T Kimura, M Takahashi, R Nakatsuka, Y Uemura, Y Sasaki & Y Sonoda

  2. First Department of Internal Medicine, Kansai Medical University, Moriguchi, Osaka, Japan

    M Murakami & T Kimura

  3. Department of Pediatrics, Kansai Medical University, Moriguchi, Osaka, Japan

    M Takahashi

  4. Department of Obstetrics and Gynecology, Kansai Medical University, Moriguchi, Osaka, Japan

    T Nakamoto & K Yasuda

  5. Department of Gynecology and Obstetrics, Fukuda Hospital, Kumamoto, Kumamoto, Japan

    K Matsui

  6. Department of Obstetrics and Gynecology, Aizenbashi Hospital, Osaka, Japan

    K Kobayashi & S Imai

  7. School of Nursing, Kyoto Prefectural University of Medicine, Kyoto, Japan

    H Asano

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  1. T Kimura
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Correspondence to Y Sonoda.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Kimura, T., Matsuoka, Y., Murakami, M. et al. In vivo dynamics of human cord blood-derived CD34− SCID-repopulating cells using intra-bone marrow injection. Leukemia 24, 162–168 (2010). https://doi.org/10.1038/leu.2009.206

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