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Stem Cell Reports. 2017 Mar 14;8(3):500-508. doi: 10.1016/j.stemcr.2017.01.015. Epub 2017 Feb 23.

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

Author information

1
Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
2
Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; 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.
3
Cell Engineering Division, BioResource Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
4
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.
5
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical Collage, 288 Nanjing Road, Tianjin 300020, China.
6
Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; 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. Electronic address: nakauchi@ims.u-tokyo.ac.jp.
7
Laboratory of Stem Cell Therapy, Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Project Division of Advanced Regenerative Medicine, The Institute of Medical Science, the University of Tokyo, Tokyo 108-8639, Japan. Electronic address: y-sato4@ims.u-tokyo.ac.jp.

Abstract

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.

KEYWORDS:

BSA; FCS; all-recombinant protein-based culture system; hematopoietic stem cell; hemopexin

PMID:
28238792
PMCID:
PMC5355634
DOI:
10.1016/j.stemcr.2017.01.015
[Indexed for MEDLINE]
Free PMC Article

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