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TISSUE-SPECIFIC STEM CELLS

Two Distinct Stem Cell Lineages in Murine Bone Marrow

Departments of ^aPhysiology,
^cDentistry and Oral Surgery, and
^fHematology Division, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan;
^bDepartment of Periodontology, Showa University Dental School, Tokyo, Japan;
^dDivision of Hematology, Department of Medicine and
^eResearch Center for Regenerative Medicine, Tokai University School of Medicine, Kanagawa, Japan;
^gCore Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama, Japan

Key Words. Hematopoietic stem cell • Mesenchymal stem cell • Transplantation • Lineage relation • Plasticity

Correspondence: Yumi Matsuzaki, M.D., Ph.D., Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Telephone: 03-5363-3117; Fax: 03-5363-3566; e-mail: penguin{at}sc.itc.keio.ac.jp

Received May 29, 2006; accepted for publication January 2, 2007.
First published online in STEM CELLS EXPRESS   January 11, 2007.



Mesenchymal stem cells (MSC), a distinct type of adult stem cell, are easy to isolate, culture, and manipulate in ex vivo culture. These cells have great plasticity and potential for therapeutic application, but their properties are poorly understood because of their low frequency and the lack of knowledge on cell surface markers and their location of origin. The present study was designed to address the undefined lineage relationship of hematopoietic and mesenchymal stem cells. Genetically marked, highly purified hematopoietic stem cells (HSCs) were transplanted into wild-type animals and, after bone marrow repopulation, the progeny were rigorously investigated for differentiation potential into mesenchymal tissues by analyzing in vitro differentiation into mesenchymal tissues. None/very little of the hematopoietic cells contributed to colony-forming units fibroblast activity and mesenchymal cell differentiation; however, unfractionated bone marrow cells resulted in extensive replacement of not only hematopoietic cells but also mesenchymal cells, including MSCs. As a result, we concluded that purified HSCs have no significant potency to differentiate into mesenchymal lineage. The data strongly suggest that hematopoietic cells and mesenchymal lineage cells are derived from individual lineage-specific stem cells. In addition, we succeeded in visualizing mesenchymal lineage cells using in vivo microimaging and immunohistochemistry. Flow cytometric analysis revealed CD140b (PDGFRβ) could be a specific marker for mesenchymal lineage cells. The results may reinforce the urgent need for a more comprehensive view of the mesenchymal stem cell identity and characteristics.

Disclosure of potential conflicts of interest is found at the end of this article.