title: Molecular analysis and differentiation capacity of adipose-derived stem cells from lymphedema tissue.
abstract: BACKGROUND
  Many breast cancer patients are plagued by the disabling complication of upper limb lymphedema after axillary surgery. Conservative treatments using massage and compression therapy do not offer a lasting relief, as they fail to address the chronic transformation of edema into excess adipose tissue. Liposuction to address the adipose nature of the lymphedema has provided an opportunity for a detailed analysis of the stromal fraction of lymphedema-associated fat to clarify the molecular mechanisms for this adipogenic transformation.
  
  
  METHODS
  Adipose-derived stem cells were harvested from human lipoaspirate of the upper extremity from age-matched patients with lymphedema (n = 3) or subcutaneous adipose tissue from control patients undergoing cosmetic procedures (n = 3). Immediately after harvest, adipose-derived stem cells were analyzed using single-cell transcriptional profiling techniques. Osteogenic, adipogenic, and vasculogenic gene expression and differentiation were assessed by quantitative real-time polymerase chain reaction and standard in vitro differentiation assays.
  
  
  RESULTS
  Differential transcriptional clusters of adipose-derived stem cells were found between lymphedema and subcutaneous fat. Interestingly, lymphedema-associated stem cells had a much higher adipogenic gene expression and enhanced ability to undergo adipogenic differentiation. Conversely, they had lower vasculogenic gene expression and diminished capability to form tubules in vitro, whereas the osteogenic differentiation capacity was not significantly altered.
  
  
  CONCLUSIONS
  Adipose-derived stem cells from extremities affected by lymphedema appear to exhibit transcriptional profiles similar to those of abdominal adipose-derived stem cells; however, their adipogenic differentiation potential is strongly increased and their vasculogenic capacity is compromised. These results suggest that the underlying pathophysiology of lymphedema drives adipose-derived stem cells toward adipogenic differentiation.
authors.affiliation: Stanford, Calif. From the Hagey Laboratory for Pediatric Regenerative Medicine; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine; and the Institute for Stem Cell Biology and Regenerative Medicine, Stanford University.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Levi
authors.forename: Jason P
authors.initials: JP
authors.lastname: Glotzbach
authors.forename: Michael
authors.initials: M
authors.lastname: Sorkin
authors.forename: Jeong
authors.initials: J
authors.lastname: Hyun
authors.forename: Michael
authors.initials: M
authors.lastname: Januszyk
authors.forename: Derrick C
authors.initials: DC
authors.lastname: Wan
authors.forename: Shuli
authors.initials: S
authors.lastname: Li
authors.forename: Emily R
authors.initials: ER
authors.lastname: Nelson
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Gurtner
mesh_terms: D050156:Adipogenesis / Q000235:genetics*; D000328:Adult; D001132:Arm; D001365:Axilla; D001943:Breast Neoplasms / Q000601:surgery; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006801:Humans; D015187:Lipectomy; D008197:Lymph Node Excision; D008209:Lymphedema / Q000209:etiology / Q000235:genetics / Q000503:physiopathology* / Q000601:surgery; D008875:Middle Aged; D011183:Postoperative Complications / Q000235:genetics / Q000503:physiopathology* / Q000601:surgery; D060888:Real-Time Polymerase Chain Reaction; D013234:Stem Cells / Q000502:physiology*; D050151:Subcutaneous Fat / Q000503:physiopathology*; D059467:Transcriptome
chemical_list: D005819:Genetic Markers