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Stem Cell Reviews and Reports

, Volume 12, Issue 2, pp 235–244 | Cite as

Adipogenic Mesenchymal Stromal Cells from Bone Marrow and Their Hematopoietic Supportive Role: Towards Understanding the Permissive Marrow Microenvironment in Acute Myeloid Leukemia

  • Yevgeniya Le
  • Sylvain Fraineau
  • Priya Chandran
  • Mitchell Sabloff
  • Marjorie Brand
  • Jessie R. Lavoie
  • Rémi Gagne
  • Michael Rosu-Myles
  • Carole L. Yauk
  • Richard B. Richardson
  • David S. Allan
Article

Abstract

Purpose

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.

Findings

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.

Conclusion

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.

Keywords

Mesenchymal stromal cells AML Hematopoietic niche Bone marrow microenvironment Adipogenesis Osteogenesis 

Notes

Acknowledgments

This work was supported by Canadian Nuclear Laboratories, the Joan Sealy Trust Fund, Faculty of Medicine, University of Ottawa and The Ottawa Hospital Foundation (Cushing Fund). We gratefully acknowledge the support from the Department of Medicine, University of Ottawa and Canadian Institutes for Health Research (New Investigator Award, DSA). RNA-sequencing work was funded by Health Canada Genomics Research and Development Initiative, Phase IV (2014–2019).

Compliance with Ethical Standards

Conflict of Interest

Authors declare no conflict of interest.

Supplementary material

12015_2015_9639_MOESM1_ESM.docx (19 kb)
ESM 1 (DOCX 18 kb)
12015_2015_9639_MOESM2_ESM.docx (15 kb)
Supplementary Table 1 (DOCX 14 kb)

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Yevgeniya Le
    • 1
  • Sylvain Fraineau
    • 2
  • Priya Chandran
    • 2
  • Mitchell Sabloff
    • 3
  • Marjorie Brand
    • 2
    • 3
  • Jessie R. Lavoie
    • 4
  • Rémi Gagne
    • 4
    • 5
  • Michael Rosu-Myles
    • 4
  • Carole L. Yauk
    • 4
    • 5
  • Richard B. Richardson
    • 1
    • 6
  • David S. Allan
    • 2
    • 3
  1. 1.Canadian Nuclear LaboratoriesChalk RiverCanada
  2. 2.Regenerative Medicine ProgramOttawa Hospital Research InstituteOttawaCanada
  3. 3.Department of MedicineUniversity of OttawaOttawaCanada
  4. 4.Centre for Biologics Evaluation, Biologics and Genetic Therapies Directorate, Health Products and Food BranchHealth CanadaOttawaCanada
  5. 5.Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety BranchHealth CanadaOttawaCanada
  6. 6.McGill Medical Physics UnitMontreal General HospitalMontrealCanada

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