title: Adipose-derived stromal vascular fraction cells isolated from old animals exhibit reduced capacity to support the formation of microvascular networks.
abstract: Adipose-derived regenerative and stem cells, defined collectively as the stromal vascular fraction (SVF), support the formation of neovascular networks at the site of implantation. The effect of advancing age on SVF cell population effectiveness towards stimulated neovascularization was evaluated.
  
  
  METHODS
  SVF was enzymatically isolated from adipose of young (ySVF, 4 months) or old (oSVF, 24 months) Fisher-344 rats, combined with type I collagen and polymerized. Encapsulated SVF was implanted subcutaneously into young Rag1 mice for two or four weeks. Angiogenic function of age-dependent SVF was also extensively evaluated in vitro using standard assays.
  
  
  RESULTS
  In vitro studies indicated no difference in angiogenic function between ySVF and oSVF (viability, proliferation, migration, and tube-formation). At two weeks post-implantation, there was no age-related difference in percent apoptosis in explanted constructs. By four weeks post-implantation, oSVF implants displayed 36% less total vessels/mm(2), 43% less perfused vessels/mm(2), and exhibited greater percent apoptosis compared to ySVF (n ≥ 12). Blocking thrombospondin-1 (Thbs-1), a protein found to be highly expressed in oSVF but not ySVF, increased the percent of perfused vascular volume and vessel diameters in oSVF constructs after two weeks compared to oSVF implants treated with control antibody.
  
  
  CONCLUSIONS
  Advancing donor age reduces the potential of adipose-derived SVF to derive a mature microcirculation, but does not hinder initial angiogenesis. However, modulation of Thbs-1 may improve this outcome. This data suggests that greater pruning, dysfunctional structural adaptation and/or poor maturation with initiation of blood flow may occur in oSVF.
authors.affiliation: Cardiovascular Innovation Institute, Jewish Hospital and University of Louisville, Louisville, KY 40202, United States.
authors.forename: Allison L
authors.initials: AL
authors.lastname: Aird
authors.affiliation: Cardiovascular Innovation Institute, Jewish Hospital and University of Louisville, Louisville, KY 40202, United States; Department of Biochemistry and Molecular Biology, Jewish Hospital and University of Louisville, Louisville, KY 40202, United States.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Nevitt
authors.affiliation: Cardiovascular Innovation Institute, Jewish Hospital and University of Louisville, Louisville, KY 40202, United States.
authors.forename: Katelyn
authors.initials: K
authors.lastname: Christian
authors.affiliation: Cardiovascular Innovation Institute, Jewish Hospital and University of Louisville, Louisville, KY 40202, United States; Department of Physiology and Biophysics, Jewish Hospital and University of Louisville, Louisville, KY 40202, United States.
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Williams
authors.affiliation: Cardiovascular Innovation Institute, Jewish Hospital and University of Louisville, Louisville, KY 40202, United States; Department of Physiology and Biophysics, Jewish Hospital and University of Louisville, Louisville, KY 40202, United States.
authors.forename: James B
authors.initials: JB
authors.lastname: Hoying
authors.affiliation: Cardiovascular Innovation Institute, Jewish Hospital and University of Louisville, Louisville, KY 40202, United States; Department of Physiology and Biophysics, Jewish Hospital and University of Louisville, Louisville, KY 40202, United States. Electronic address: amanda.leblanc@louisville.edu.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: LeBlanc
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000375:Aging; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D007511:Ischemia / Q000628:therapy; D008297:Male; D051379:Mice; D055806:Microvessels; D018919:Neovascularization, Physiologic; D051381:Rats; D011916:Rats, Inbred F344; D017154:Stromal Cells / Q000378:metabolism*; D019700:Thrombospondin 1 / Q000378:metabolism*; D066253:Vascular Remodeling
chemical_list: D015415:Biomarkers; D019700:Thrombospondin 1
keywords: Aging; Angiogenesis; Apoptosis; Inosculation; Ischemia; Maturation; Thrombospondin-1; Vascular remodeling