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Blood, 1 March 2006, Vol. 107, No. 5, pp. 1878-1887.
Prepublished online as a Blood First Edition Paper on November 10, 2005; DOI 10.1182/blood-2005-06-2211.
Previous Article | Next Article 
Submitted June 2, 2005
Accepted October 26, 2005
Reconstitution of the functional human hematopoietic microenvironment derived from human mesenchymal stem cells in the murine bone marrow compartment
Yukari Muguruma, Takashi Yahata, Hiroko Miyatake, Tadayuki Sato, Tomoko Uno, Jobu Itoh, Shunichi Kato, Mamoru Ito, Tomomitsu Hotta, and Kiyoshi Ando*
Division of Hematopoiesis, Research Center of Regenerative Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
Division of Hematopoiesis, Research Center of Regenerative Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan; Department of Hematology, Tokai University School of Medicine, Isehara, Kanagawa, Japan
Teaching and Research Support Center, Tokai University School of Medicine, Isehara, Kanagawa, Japan
Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
Central Institute for Experimental Animal, Kawasaki, Kanagawa, Japan
* Corresponding author; email: andok{at}keyaki.cc.u-tokai.ac.jp.
Hematopoiesis is maintained by specific interactions between both hematopoietic and non-hematopoietic cells. While hematopoietic stem cells (HSCs) have been extensively studied both in vitro and in vivo, little is known about the in vivo characteristics of stem cells of the non-hematopoietic component, known as mesenchymal stem cells (MSCs). Here we have visualized and characterized human MSCs in vivo following intramedullary transplantation of enhanced green fluorescent protein-marked human MSCs (eGFP-MSCs) into the bone marrow (BM) of nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. During 4 to 10 weeks after transplantation, eGFP-MSCs that engrafted in murine BM integrated into the hematopoietic microenvironment (HME) of the host mouse. They differentiated into pericytes, myofibroblasts, BM stromal cells, osteocytes in bone, bone-lining osteoblasts, and endothelial cells, which constituted the functional components of the BM HME. The presence of human MSCs in murine BM resulted in increase in functionally and phenotypically primitive human hematopoietic cells. Human MSC-derived cells that reconstituted the hematopoietic microenvironment appeared to contribute to the maintenance of human hematopoiesis by actively interacting with primitive human hematopoietic cells.

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