title: Mesenchymal stem cell-organized bone marrow elements: an alternative hematopoietic progenitor resource.
abstract: Bone marrow-derived mesenchymal stem cells (BMMSCs) are multipotent postnatal stem cells that have been used for the treatment of bone defects and graft-versus-host diseases in clinics. In this study, we found that subcutaneously transplanted human BMMSCs are capable of organizing hematopoietic progenitors of recipient origin. These hematopoietic cells expressed multiple lineages of hematopoietic cell associated markers and were able to rescue lethally irradiated mice, with successful engraftment in the recipient, suggesting a potential bone marrow (BM) resource for stem cell therapies. Furthermore, we found that platelet-derived growth factor (PDGF) promotes the formation of BMMSC-generated BM niches through upregulation of beta-catenin, implying that the PDGF pathway contributes to the formation of ectopic BM. These results indicate that the BMMSC-organized BM niche system represents a unique hematopoietic progenitor resource possessing potential clinical value.
authors.affiliation: National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miura
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Gao
authors.forename: Masako
authors.initials: M
authors.lastname: Miura
authors.forename: Byoung-Moo
authors.initials: BM
authors.lastname: Seo
authors.forename: Wataru
authors.initials: W
authors.lastname: Sonoyama
authors.forename: WanJun
authors.initials: W
authors.lastname: Chen
authors.forename: Stan
authors.initials: S
authors.lastname: Gronthos
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Songtao
authors.initials: S
authors.lastname: Shi
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D006085:Graft Survival; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010012:Osteogenesis / Q000187:drug effects; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D034741:RNA, Small Interfering; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014916:Whole-Body Irradiation
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D034741:RNA, Small Interfering; D020797:Receptor, Platelet-Derived Growth Factor beta