Reconstitution of the functional human hematopoietic microenvironment derived from human mesenchymal stem cells in the murine bone marrow compartment

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 compone...

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Bibliographic Details
Published in:Blood 2006-03, Vol.107 (5), p.1878-1887
Main Authors: Muguruma, Yukari, Yahata, Takashi, Miyatake, Hiroko, Sato, Tadayuki, Uno, Tomoko, Itoh, Jobu, Kato, Shunichi, Ito, Mamoru, Hotta, Tomomitsu, Ando, Kiyoshi
Format: Article
Language:English
Subjects:
Animals
Bone Marrow Cells - cytology
Bone Marrow Cells - physiology
Cell Differentiation - physiology
Hematopoiesis - physiology
Humans
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells - cytology
Mesenchymal Stem Cells - physiology
Mice
Mice, Inbred NOD
Mice, SCID
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2005-06-2211