An All-Recombinant Protein-Based Culture System Specifically Identifies Hematopoietic Stem Cell Maintenance Factors

Aki Ieyasu; Reiko Ishida; Takaharu Kimura; Maiko Morita; Adam C. Wilkinson; Kazuhiro Sudo; Toshinobu Nishimura; Jun Ohehara; Yoko Tajima; Chen-Yi Lai; Makoto Otsu; Yukio Nakamura; Hideo Ema; Hiromitsu Nakauchi; Satoshi Yamazaki

doi:10.1016/j.stemcr.2017.01.015

Stem Cell Reports (Mar 2017)

An All-Recombinant Protein-Based Culture System Specifically Identifies Hematopoietic Stem Cell Maintenance Factors

Aki Ieyasu,
Reiko Ishida,
Takaharu Kimura,
Maiko Morita,
Adam C. Wilkinson,
Kazuhiro Sudo,
Toshinobu Nishimura,
Jun Ohehara,
Yoko Tajima,
Chen-Yi Lai,
Makoto Otsu,
Yukio Nakamura,
Hideo Ema,
Hiromitsu Nakauchi,
Satoshi Yamazaki

Affiliations

Aki Ieyasu: Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Reiko Ishida: Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Takaharu Kimura: Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Maiko Morita: Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Adam C. Wilkinson: Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Kazuhiro Sudo: Cell Engineering Division, BioResource Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan
Toshinobu Nishimura: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Lorry I. Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA 94305-5461, USA
Jun Ohehara: Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Yoko Tajima: Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Chen-Yi Lai: Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Makoto Otsu: Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Yukio Nakamura: Cell Engineering Division, BioResource Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan
Hideo Ema: Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical Collage, 288 Nanjing Road, Tianjin 300020, China
Hiromitsu Nakauchi: Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Satoshi Yamazaki: Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan

DOI: https://doi.org/10.1016/j.stemcr.2017.01.015
Journal volume & issue: Vol. 8, no. 3
pp. 500 – 508

Abstract

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Hematopoietic stem cells (HSCs) are considered one of the most promising therapeutic targets for the treatment of various blood disorders. However, due to difficulties in establishing stable maintenance and expansion of HSCs in vitro, their insufficient supply is a major constraint to transplantation studies. To solve these problems we have developed a fully defined, all-recombinant protein-based culture system. Through this system, we have identified hemopexin (HPX) and interleukin-1α as responsible for HSC maintenance in vitro. Subsequent molecular analysis revealed that HPX reduces intracellular reactive oxygen species levels within cultured HSCs. Furthermore, bone marrow immunostaining and 3D immunohistochemistry revealed that HPX is expressed in non-myelinating Schwann cells, known HSC niche constituents. These results highlight the utility of this fully defined all-recombinant protein-based culture system for reproducible in vitro HSC culture and its potential to contribute to the identification of factors responsible for in vitro maintenance, expansion, and differentiation of stem cell populations.

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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