Adipocyte differentiation of human marrow mesenchymal stem cells reduces the supporting capacity for hematopoietic progenitors but not for severe combined immunodeficiency repopulating cells.
Bone marrow stromal cells provide a microenvironment for hematopoiesis. Adipocytes are the major stromal cell phenotype in bone marrow, but their function in hematopoiesis is poorly understood. In this study, we compared the hematopoietic-supporting capacity of adipocytes and their progenitor, mesenchymal stem cells (MSCs), by culturing human cord blood (CB) CD34+CD38- hematopoietic progenitor cells (HPCs) on a layer of adipocytes or MSCs. CB CD34+CD38- cells cultured on MSCs generated higher proportions of CD34+CD38- HPCs and colony-forming cells than those cultures on a layer of adipocytes, indicating an inferior hematopoietic support by adipocytes. However, CB CD34+CD38- HPCs cultured on MSCs and adipocytes were equally capable of reconstituting human hematopoiesis in non-obese diabetic/severe combined immunodeficient disease (NOD/SCID) mice. These findings show that differentiation of MSCs into adipocytes is accompanied by the loss of capacity to support mature HPCs, but not transplantable SCID-repopulating cells.
Ookura
Nobuhiko
N
Division of Hematology, Department of Internal Medicine, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Hyogo 663-8501, Japan.
Fujimori
Yoshihiro
Y
Nishioka
Keisuke
K
Kai
Shunro
S
Hara
Hiroshi
H
Ogawa
Hiroyasu
H
D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D017690:Cell Transplantation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000637:transplantation; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D016513:Mice, SCID; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016511:Severe Combined Immunodeficiency / Q000473:pathology*; D014183:Transplantation, Heterologous
D018952:Antigens, CD34; D016207:Cytokines; D006133:Growth Substances; D012333:RNA, Messenger