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Evidence of in situ proliferation of adult adipose tissue-derived progenitor cells: influence of fat mass microenvironment and growth
- Source :
- Journal of Clinical Endocrinology and Metabolism, Journal of Clinical Endocrinology and Metabolism, 2008, 93 (10), pp.4098-106. ⟨10.1210/jc.2008-0044⟩
- Publication Year :
- 2008
-
Abstract
- International audience; CONTEXT: Adipocyte formation in human adult adipose tissue (hAT) originates from resident progenitor cell differentiation in the stroma vascular fraction of the AT. The processes involved in the self-renewal of this cell population remain to be defined. OBJECTIVE: The objective was to study in situ and in vitro hAT progenitor cell (defined as CD34(+)/CD31(-) cells) proliferation. DESIGN AND PARTICIPANTS: In situ progenitor cell proliferation was assessed by immunohistochemistry and flow cytometry analyses on hAT from lean to obese subjects using the proliferation marker Ki-67. The effects of adipokines, hypoxia, and conditioned media (CM) from adipocytes, capillary endothelial cells, and macrophages isolated by an immunoselection approach were studied on hAT progenitor cell growth. Cell death in hAT was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein end labeling method. RESULTS: Ki-67-positive staining was observed in AT progenitor cells. Fat mass enlargement in obese patients was associated with an increased Ki-67(+) progenitor cell population together with a new fraction of small adipocytes and increased cell death. HIF-1alpha mRNA expression in freshly harvested progenitor cells was positively correlated with body mass index. Adipocyte- and capillary endothelial cell-CM, hypoxia, leptin, IL-6, lysophosphatidic acid, and vascular endothelial growth factor, all increased hAT progenitor cell proliferation in vitro. Macrophage-CM had an antiproliferative effect that was suppressed by an antioxidant. CONCLUSIONS: The fraction of proliferative progenitor cells in adult hAT is modulated by the degree of adiposity. Changes in the progenitor cell microenvironment involving adipokines, hypoxia, and oxidative stress might play a key role in the control of the self-renewal of the local pool of AT progenitor cells.
- Subjects :
- MESH: Cell Death
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
CD34
Adipose tissue
Antigens, CD34
Biochemistry
chemistry.chemical_compound
Endocrinology
Adipocyte
MESH: Obesity
MESH: Cell Size
Cells, Cultured
education.field_of_study
MESH: Culture Media, Conditioned
Cell Death
Stem Cells
Cell Differentiation
Platelet Endothelial Cell Adhesion Molecule-1
Adipose Tissue
Female
Stem cell
MESH: Adipose Tissue
MESH: Oxygen
MESH: Cells, Cultured
MESH: Cell Differentiation
Adult
medicine.medical_specialty
Human Development
Population
MESH: Stem Cells
Biology
MESH: Adipokines
Adipokines
Internal medicine
MESH: Human Development
MESH: Cell Proliferation
parasitic diseases
medicine
[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology
Humans
Proliferation Marker
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Obesity
Progenitor cell
education
Cell Proliferation
Cell Size
MESH: Humans
Cell growth
Biochemistry (medical)
MESH: Adult
MESH: Antigens, CD31
Extracellular Fluid
MESH: Antigens, CD34
Oxygen
chemistry
MESH: Extracellular Fluid
Culture Media, Conditioned
MESH: Female
Subjects
Details
- ISSN :
- 0021972X and 19457197
- Volume :
- 93
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Accession number :
- edsair.doi.dedup.....655fe8de9bfbd44fed0a4467f0c7f9df