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Alcohol Induces Proliferation of Multipotential Mesenchymal Stromal Cells and Their Differentiation into Adipocytes
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.578.2
Subject(s) - mesenchymal stem cell , stromal cell , haematopoiesis , osteoblast , stem cell , microbiology and biotechnology , bone marrow , progenitor cell , adipogenesis , endocrinology , cellular differentiation , osteoporosis , cell , medicine , cell culture , biology , chemistry , cancer research , immunology , biochemistry , in vitro , genetics , gene
During aging, bone marrow (BM) fat increases and hematopoietic stem cells (HSCs) decrease, converting the marrow from red to yellow. Multipotential Mesenchymal Stromal Cells (MMSCs) give rise to various cell types comprising the BM microenvironment, that regulate HSCs differently. MMSC differentiation into osteoblasts, provides a favorable microenvironment where as into adipocytes is less supportive for HSCs. Therefore accumulation of adipocytes in BM may contribute to osteoporosis and hematopoietic deficiencies of aging. In the present study, changes in various stem cell populations with aging in human subjects were studied, BM‐MMSCs were enumerated as either CD45lo Stro‐1+ cells or Fibroblast Colony Forming Cells (FCFC). Stro‐1+ cells declined slightly with age but FCFC showed no significant changes. However, when subjects were segregated into drinkers of alcohol versus non‐drinkers, the former had fewer FCFCs than the latter. The potential basis of this observation was studied by exposing a cloned mouse MMSC cell line, OMA‐AD to various concentrations of ethanol. Lower concentrations (5–50 mM) increased proliferation as compared to controls and also induced adipocytic differentiation. Higher concentrations of ethanol (>300 mM) were progressively toxic to MMSC. Potentially, the loss of FCFC and by implication MMSC, in alcohol drinkers might occur by promotion of differentiation to adipocytes leading to inhibition of osteoblast production. This, in turn, may have implications for impaired fracture repair, increased osteoporosis and hematopoietic microenvironmental defects in the elderly who consume alcohol.