Diet-induced obesity alters the differentiation potential of stem cells isolated from bone marrow, adipose tissue and infrapatellar fat pad: the effects of free fatty acids.

dc.contributor.author

Wu, C-L

dc.contributor.author

Diekman, BO

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Jain, D

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Guilak, F

dc.coverage.spatial

England

dc.date.accessioned

2013-08-31T15:48:50Z

dc.date.accessioned

2013-08-31T15:49:32Z

dc.date.accessioned

2013-08-31T15:52:22Z

dc.date.issued

2013-08

dc.description.abstract

INTRODUCTION: Obesity is a major risk factor for several musculoskeletal conditions that are characterized by an imbalance of tissue remodeling. Adult stem cells are closely associated with the remodeling and potential repair of several mesodermally derived tissues such as fat, bone and cartilage. We hypothesized that obesity would alter the frequency, proliferation, multipotency and immunophenotype of adult stem cells from a variety of tissues. MATERIALS AND METHODS: Bone marrow-derived mesenchymal stem cells (MSCs), subcutaneous adipose-derived stem cells (sqASCs) and infrapatellar fat pad-derived stem cells (IFP cells) were isolated from lean and high-fat diet-induced obese mice, and their cellular properties were examined. To test the hypothesis that changes in stem cell properties were due to the increased systemic levels of free fatty acids (FFAs), we further investigated the effects of FFAs on lean stem cells in vitro. RESULTS: Obese mice showed a trend toward increased prevalence of MSCs and sqASCs in the stromal tissues. While no significant differences in cell proliferation were observed in vitro, the differentiation potential of all types of stem cells was altered by obesity. MSCs from obese mice demonstrated decreased adipogenic, osteogenic and chondrogenic potential. Obese sqASCs and IFP cells showed increased adipogenic and osteogenic differentiation, but decreased chondrogenic ability. Obese MSCs also showed decreased CD105 and increased platelet-derived growth factor receptor α expression, consistent with decreased chondrogenic potential. FFA treatment of lean stem cells significantly altered their multipotency but did not completely recapitulate the properties of obese stem cells. CONCLUSIONS: These findings support the hypothesis that obesity alters the properties of adult stem cells in a manner that depends on the cell source. These effects may be regulated in part by increased levels of FFAs, but may involve other obesity-associated cytokines. These findings contribute to our understanding of mesenchymal tissue remodeling with obesity, as well as the development of autologous stem cell therapies for obese patients.

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/23164698

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ijo2012171

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1476-5497

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https://hdl.handle.net/10161/7785

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eng

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Springer Science and Business Media LLC

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Int J Obes (Lond)

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10.1038/ijo.2012.171

dc.relation.replaces

http://hdl.handle.net/10161/7783

dc.relation.replaces

10161/7783

dc.relation.replaces

http://hdl.handle.net/10161/7784

dc.relation.replaces

10161/7784

dc.subject

Adipogenesis

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Adipose Tissue

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Animals

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Cell Culture Techniques

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Cell Differentiation

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Cell Proliferation

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Cells, Cultured

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Diet, High-Fat

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Fatty Acids, Nonesterified

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Male

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Mesenchymal Stromal Cells

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Mice

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Mice, Inbred C57BL

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Mice, Obese

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Obesity

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Patella

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Risk Factors

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Subcutaneous Fat

dc.title

Diet-induced obesity alters the differentiation potential of stem cells isolated from bone marrow, adipose tissue and infrapatellar fat pad: the effects of free fatty acids.

dc.type

Journal article

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/23164698

pubs.begin-page

1079

pubs.end-page

1087

pubs.issue

8

pubs.organisational-group

Biomedical Engineering

pubs.organisational-group

Duke

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Pratt School of Engineering

pubs.publication-status

Published

pubs.volume

37

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