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

• Published in: Stem cells translational medicine Vol. 8; no. 6; pp. 606 - 616
• Main Authors: Lv, Tao, Gu, Yunpeng, Bi, Jianhai, Kang, Ning, Yang, Zhigang, Fu, Xin, Wang, Qian, Yan, Li, Liu, Xia, Cao, Yilin, Xiao, Ran
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-06-2019; Oxford University Press
• Subjects: Adipocytes; Adipose Tissue - metabolism; Adipose Tissue - pathology; Adipose Tissue - transplantation; Adipose‐derived stem cells; Animals; Antigens, CD - genetics; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - genetics; Antigens, Differentiation, Myelomonocytic - metabolism; Biomedical materials; Cardiovascular disease; Cell Hypoxia; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell viability; Data analysis; Drug dosages; Energy metabolism; Fat grafting; Fructose; Fructose 1,6‐bisphosphate; Fructosediphosphates - pharmacology; Gene expression; Gene Expression - drug effects; Glycerol; Glycerol-3-Phosphate Dehydrogenase (NAD+) - metabolism; Graft Survival - drug effects; Graft Survival - physiology; Growth factors; Humans; Hypoxia; Immunology; Inflammation; Injections, Intraperitoneal; Ischemia; Laboratory animals; Medical research; Metabolism; Mice; Mice, Nude; Patients; Plastic surgery; Protective Agents - pharmacology; Reconstructive surgery; Regenerative medicine; Stem cell transplantation; Stem cells; Stem Cells - cytology; Stem Cells - drug effects; Stem Cells - metabolism; Tissue Engineering and Regenerative Medicine; Transplantation; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Volume retention; von Willebrand Factor - genetics; von Willebrand Factor - metabolism; Beijing China; China; Fructose 1,6-bisphosphate; Adipose-derived stem cells; Volume retention; Ischemia; Fat grafting
• ISSN: 2157-6564; 2157-6580
• DOI: 10.1002/sctm.18-0212

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
Fat grafting has been regarded as a promising regenerative and cell‐directed therapy, but the challenge is its survival and longevity after implantation because of ischemia. We now show that fructose 1,6‐bisphosphate improves fat graft long‐term survival by enhancing adipocyte viability and function, increasing vascularization, reducing inflammation, and promoting adipose‐derived stem cells viability in fat graft in ischemia conditions.