Mesenchymal stem cell-organized bone marrow elements: an alternative hematopoietic progenitor resource.
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.
Miura
Yasuo
Y
National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland.
Gao
Zhigang
Z
Miura
Masako
M
Seo
Byoung-Moo
BM
Sonoyama
Wataru
W
Chen
WanJun
W
Gronthos
Stan
S
Zhang
Li
L
Shi
Songtao
S
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
D020574:Proto-Oncogene Proteins c-sis; D034741:RNA, Small Interfering; D020797:Receptor, Platelet-Derived Growth Factor beta