title: Diabetes impairs the angiogenic potential of adipose-derived stem cells by selectively depleting cellular subpopulations.
abstract: BACKGROUND
  Pathophysiologic changes associated with diabetes impair new blood vessel formation and wound healing. Mesenchymal stem cells derived from adipose tissue (ASCs) have been used clinically to promote healing, although it remains unclear whether diabetes impairs their functional and therapeutic capacity.
  
  
  METHODS
  In this study, we examined the impact of diabetes on the murine ASC niche as well as on the potential of isolated cells to promote neovascularization in vitro and in vivo. A novel single-cell analytical approach was used to interrogate ASC heterogeneity and subpopulation dynamics in this pathologic setting.
  
  
  RESULTS
  Our results demonstrate that diabetes alters the ASC niche in situ and that diabetic ASCs are compromised in their ability to establish a vascular network both in vitro and in vivo. Moreover, these diabetic cells were ineffective in promoting soft tissue neovascularization and wound healing. Single-cell transcriptional analysis identified a subpopulation of cells which was diminished in both type 1 and type 2 models of diabetes. These cells were characterized by the high expression of genes known to be important for new blood vessel growth.
  
  
  CONCLUSIONS
  Perturbations in specific cellular subpopulations, visible only on a single-cell level, represent a previously unreported mechanism for the dysfunction of diabetic ASCs. These data suggest that the utility of autologous ASCs for cell-based therapies in patients with diabetes may be limited and that interventions to improve cell function before application are warranted.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Rennert
authors.forename: Michael
authors.initials: M
authors.lastname: Sorkin
authors.forename: Michael
authors.initials: M
authors.lastname: Januszyk
authors.forename: Dominik
authors.initials: D
authors.lastname: Duscher
authors.forename: Revanth
authors.initials: R
authors.lastname: Kosaraju
authors.forename: Michael T
authors.initials: MT
authors.lastname: Chung
authors.forename: James
authors.initials: J
authors.lastname: Lennon
authors.forename: Anika
authors.initials: A
authors.lastname: Radiya-Dixit
authors.forename: Shubha
authors.initials: S
authors.lastname: Raghvendra
authors.forename: Zeshaan N
authors.initials: ZN
authors.lastname: Maan
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hu
authors.forename: Jayakumar
authors.initials: J
authors.lastname: Rajadas
authors.forename: Melanie
authors.initials: M
authors.lastname: Rodrigues
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Gurtner
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D055153:Stem Cell Niche / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology*; D014945:Wound Healing / Q000502:physiology