title: Obesity inhibits the osteogenic differentiation of human adipose-derived stem cells.
abstract: BACKGROUND
  Craniomaxillofacial defects secondary to trauma, tumor resection, or congenital malformations are frequent unmet challenges, due to suboptimal alloplastic options and limited autologous tissues such as bone. Significant advances have been made in the application of adipose-derived stem/stromal cells (ASCs) in the pre-clinical and clinical settings as a cell source for tissue engineering approaches. To fully realize the translational potential of ASCs, the identification of optimal donors for ASCs will ensure the successful implementation of these cells for tissue engineering approaches. In the current study, the impact of obesity on the osteogenic differentiation of ASCs was investigated.
  
  
  METHODS
  ASCs isolated from lean donors (body mass index <25; lnASCs) and obese donors (body mass index >30; obASCs) were induced with osteogenic differentiation medium as monolayers in an estrogen-depleted culture system and on three-dimensional scaffolds. Critical size calvarial defects were generated in male nude mice and treated with scaffolds implanted with lnASCs or obASCs.
  
  
  RESULTS
  lnASCs demonstrated enhanced osteogenic differentiation in monolayer culture system, on three-dimensional scaffolds, and for the treatment of calvarial defects, whereas obASCs were unable to induce similar levels of osteogenic differentiation in vitro and in vivo. Gene expression analysis of lnASCs and obASCs during osteogenic differentiation demonstrated higher levels of osteogenic genes in lnASCs compared to obASCs.
  
  
  CONCLUSIONS
  Collectively, these results indicate that obesity reduces the osteogenic differentiation capacity of ASCs such that they may have a limited suitability as a cell source for tissue engineering.
authors.affiliation: Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70112, USA. alin1@tulane.edu.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Strong
authors.affiliation: Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70112, USA. rhunter5@tulane.edu.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Hunter
authors.affiliation: Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70112, USA. rjones25@tulane.edu.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jones
authors.affiliation: Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70112, USA. abowles@tulane.edu.
authors.forename: Annie C
authors.initials: AC
authors.lastname: Bowles
authors.affiliation: Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70112, USA. mdutreil@tulane.edu.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Dutreil
authors.affiliation: Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70112, USA. dgaupp@tulane.edu.
authors.forename: Dina
authors.initials: D
authors.lastname: Gaupp
authors.affiliation: Department of Biological and Agricultural Engineering, Louisiana State University, Baton Rouge, LA, 70803, USA. danielhayes@lsu.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hayes
authors.affiliation: Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70112, USA. jgimble@tulane.edu.|LaCell LLC, New Orleans, LA, 70112, USA. jgimble@tulane.edu.|Department of Surgery, Tulane University School of Medicine, New Orleans, LA, 70112, USA. jgimble@tulane.edu.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gimble
authors.affiliation: Department of Surgery, Division of Plastic Surgery, University of Michigan, Ann Arbor, MI, USA. blevi@med.umich.edu.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Levi
authors.affiliation: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70803, USA. mcnulty@lsu.edu.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: McNulty
authors.affiliation: Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70112, USA. bbunnell@tulane.edu.|Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, 70112, USA. bbunnell@tulane.edu.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Bunnell
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D003094:Collagen / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency; D019344:Lactic Acid / Q000494:pharmacology; D008819:Mice, Nude; D009765:Obesity / Q000235:genetics / Q000473:pathology*; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D011100:Polyglycolic Acid / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012886:Skull / Q000473:pathology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013851:Thinness / Q000235:genetics / Q000473:pathology; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen
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