Two distinct stem cell lineages in murine bone marrow

¹ Department of Physiology, Keio University School of Medicine, Tokyo, Japan; Department of Periodontology, Showa University Dental School, Tokyo, Japan
² Department of Physiology, Keio University School of Medicine; Department of Dentistry and Oral Surgery, Keio University School of Medicine, Tokyo, Japan
³ Department of Physiology, Keio University School of Medicine; CREST, JST, Tokyo, Japan
⁴ Division of Hematology, Department of Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan; Research Center for Regenerative Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
⁵ Department of Physiology, Keio University School of Medicine, Tokyo, Japan; CREST, JST, Tokyo, Japan
⁶ Department of Periodontology, Showa University Dental School, Tokyo, Japan
⁷ Department of Physiology, Keio University School of Medicine, Tokyo, Japan; Hematology Division, Department of Internal Medicine, Keio University School of Medicine, Isehara, Kanagawa, Japan

^* To whom correspondence should be addressed. E-mail: penguin{at}sc.itc.keio.ac.jp.

	Abstract

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 due to 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 their in vitro differentiation into mesenchymal tissues. None/very little of the hematopoietic cells contributed to CFU-F 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 do not have any 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 micro imaging and immuno-histochemistry. Flowcytometric analysis revealed CD140b (PDGFR) 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.