title: Reconstitution of the functional human hematopoietic microenvironment derived from human mesenchymal stem cells in the murine bone marrow compartment.
abstract: 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.
authors.affiliation: Division of Hematopoiesis, Research Center of Regenerative Medicine, Tokai University School of Medicine, Boseidai, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Muguruma
authors.forename: Takashi
authors.initials: T
authors.lastname: Yahata
authors.forename: Hiroko
authors.initials: H
authors.lastname: Miyatake
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Sato
authors.forename: Tomoko
authors.initials: T
authors.lastname: Uno
authors.forename: Jobu
authors.initials: J
authors.lastname: Itoh
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kato
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ito
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Hotta
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D006410:Hematopoiesis / Q000502:physiology*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID