title: Adipogenic Mesenchymal Stromal Cells from Bone Marrow and Their Hematopoietic Supportive Role: Towards Understanding the Permissive Marrow Microenvironment in Acute Myeloid Leukemia.
abstract: The role of bone marrow-derived mesenchymal stem/stromal cells (MSCs) in creating a permissive microenvironment that supports the emergence and progression of acute myeloid leukemia (AML) is not well established. We investigated the extent to which adipogenic differentiation in normal MSCs alters hematopoietic supportive capacity and we undertook an in-depth comparative study of human bone marrow MSCs derived from newly diagnosed AML patients and healthy donors, including an assessment of adipogenic differentiation capacity.
  
  
  
  MSCs from healthy controls with partial induction of adipogenic differentiation, in comparison to MSCs undergoing partial osteogenic differentiation, expressed increased levels of hematopoietic factors and induced greater proliferation, decreased quiescence and reduced in vitro hematopoietic colony forming capacity of CD34(+) hematopoietic stem and progenitor cells (HSPCs). Moreover, we observed that AML-derived MSCs had markedly increased adipogenic potential and delayed osteogenic differentiation, while maintaining normal morphology and viability. AML-derived MSCs, however, possessed reduced proliferative capacity and decreased frequency of subendothelial quiescent MSCs compared to controls.
  
  
  
  Our results support the notion of a bone marrow microenvironment characterized by increased propensity toward adipogenesis in AML, which may negatively impact normal hematopoiesis. Larger confirmatory studies are needed to understand the impact of various clinical factors. Novel leukemia treatments aimed at normalizing bone marrow niches may enhance the competitive advantage of normal hematopoietic progenitors over leukemia cells.
authors.affiliation: Canadian Nuclear Laboratories, Chalk River, ON, K0J 1 J0, Canada.
authors.forename: Yevgeniya
authors.initials: Y
authors.lastname: Le
authors.affiliation: Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Rd., Box 704, Ottawa, ON, K1H 8L6, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Fraineau
authors.affiliation: Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Rd., Box 704, Ottawa, ON, K1H 8L6, Canada.
authors.forename: Priya
authors.initials: P
authors.lastname: Chandran
authors.affiliation: Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Sabloff
authors.affiliation: Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Rd., Box 704, Ottawa, ON, K1H 8L6, Canada.|Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Brand
authors.affiliation: Centre for Biologics Evaluation, Biologics and Genetic Therapies Directorate, Health Products and Food Branch, Health Canada, Ottawa, ON, Canada.
authors.forename: Jessie R
authors.initials: JR
authors.lastname: Lavoie
authors.affiliation: Centre for Biologics Evaluation, Biologics and Genetic Therapies Directorate, Health Products and Food Branch, Health Canada, Ottawa, ON, Canada.|Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, ON, Canada.
authors.forename: Rémi
authors.initials: R
authors.lastname: Gagne
authors.affiliation: Centre for Biologics Evaluation, Biologics and Genetic Therapies Directorate, Health Products and Food Branch, Health Canada, Ottawa, ON, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Rosu-Myles
authors.affiliation: Centre for Biologics Evaluation, Biologics and Genetic Therapies Directorate, Health Products and Food Branch, Health Canada, Ottawa, ON, Canada.|Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, ON, Canada.
authors.forename: Carole L
authors.initials: CL
authors.lastname: Yauk
authors.affiliation: Canadian Nuclear Laboratories, Chalk River, ON, K0J 1 J0, Canada. richard.richardson@cnl.ca.|McGill Medical Physics Unit, Montreal General Hospital, Montreal, QC, Canada. richard.richardson@cnl.ca.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Richardson
authors.affiliation: Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Rd., Box 704, Ottawa, ON, K1H 8L6, Canada. daallan@ohri.ca.|Department of Medicine, University of Ottawa, Ottawa, ON, Canada. daallan@ohri.ca.
authors.forename: David S
authors.initials: DS
authors.lastname: Allan
mesh_terms: D050156:Adipogenesis / Q000502:physiology*; D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000502:physiology; D001854:Bone Marrow Cells / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008875:Middle Aged; D055153:Stem Cell Niche / Q000502:physiology*
keywords: AML; Adipogenesis; Bone marrow microenvironment; Hematopoietic niche; Mesenchymal stromal cells; Osteogenesis