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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 | Table of Contents | Next Article 
HEMATOPOIESIS
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
From the Division of Hematopoiesis, Research Center of Regenerative Medicine, Department of Hematology, Teaching and Research Support Center, Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan; and the Central Institute for Experimental Animals, Kawasaki, Kanagawa, Japan.
Hematopoiesis is maintained by specific interactions between both hematopoietic and nonhematopoietic cells. Whereas 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 nonhematopoietic 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. Between 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 an increase in functionally and phenotypically primitive human hematopoietic cells. Human MSC-derived cells that reconstituted the HME appeared to contribute to the maintenance of human hematopoiesis by actively interacting with primitive human hematopoietic cells.
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