Fructose 1,6-Bisphosphate as a Protective Agent for Experimental Fat Grafting

Stem Cells Transl Med. 2019 Jun;8(6):606-616. doi: 10.1002/sctm.18-0212. Epub 2019 Feb 18.

Abstract

Fat grafting procedures are considered to be a promising regenerative, cell-directed therapy; however, their survival is mainly influenced by ischemia condition. Fructose 1,6-bisphosphate (FBP), as an intermediate in energy metabolism, has the potential to rescue cells and tissues from hypoxic-ischemic circumstances. In the present study, human lipoaspirates were grafted subcutaneously into nude mice followed by a daily intraperitoneal injection of FBP at different doses for 7 days. Next, the grafts were harvested at different time points till 12 weeks postimplantation and were evaluated for cell viability and function, tissue revascularization and inflammatory cell infiltration using histological analysis, whole-mount living tissue imaging, glycerol 3-phosphate dehydrogenase activity assays, and quantitative analysis of gene expression. The results demonstrated that exogenous FBP administration could attenuate the volume and weight reduction of fat graft; meanwhile, FBP enhanced adipocyte viability and function, increased blood vessel formation, and decreased inflammation. Moreover, in vitro cell experiments showed that FBP could promote adipose-derived stem cell viability and vascular endothelial growth factor (VEGF) mRNA expression in ischemia conditions. Our study indicates that FBP can be used as a protective agent for fat grafting and may be applied in stem cell-based regenerative medicine. Stem Cells Translational Medicine 2019;8:606-616.

Keywords: Adipose-derived stem cells; Fat grafting; Fructose 1,6-bisphosphate; Ischemia; Volume retention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Adipose Tissue / transplantation*
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Cell Hypoxia
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Fructosediphosphates / pharmacology*
  • Gene Expression / drug effects
  • Glycerol-3-Phosphate Dehydrogenase (NAD+) / metabolism
  • Graft Survival / drug effects*
  • Graft Survival / physiology
  • Humans
  • Injections, Intraperitoneal
  • Mice
  • Mice, Nude
  • Protective Agents / pharmacology*
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • von Willebrand Factor / genetics
  • von Willebrand Factor / metabolism

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • Fructosediphosphates
  • Protective Agents
  • Vascular Endothelial Growth Factor A
  • von Willebrand Factor
  • Glycerol-3-Phosphate Dehydrogenase (NAD+)
  • fructose-1,6-diphosphate