Advertisement
Research Article| Volume 60, ISSUE 3, P272-278, March 2007

Download started.

Ok

VEGF gene therapy for the survival of transplanted fat tissue in nude mice

  • C.G. Yi
    Affiliations
    Department of Plastic Surgery, Xijing Hospital, The Fourth Military Medical University, #15 Changlexilu, Xi’an City, Shaanxi Province 710032, China
    Search for articles by this author
  • W. Xia
    Affiliations
    Department of Plastic Surgery, Xijing Hospital, The Fourth Military Medical University, #15 Changlexilu, Xi’an City, Shaanxi Province 710032, China
    Search for articles by this author
  • L.X. Zhang
    Affiliations
    Department of Plastic Surgery, Xijing Hospital, The Fourth Military Medical University, #15 Changlexilu, Xi’an City, Shaanxi Province 710032, China
    Search for articles by this author
  • Y. Zhen
    Affiliations
    Department of Plastic Surgery, Xijing Hospital, The Fourth Military Medical University, #15 Changlexilu, Xi’an City, Shaanxi Province 710032, China
    Search for articles by this author
  • M.G. Shu
    Affiliations
    Department of Plastic Surgery, Xijing Hospital, The Fourth Military Medical University, #15 Changlexilu, Xi’an City, Shaanxi Province 710032, China
    Search for articles by this author
  • Y. Han
    Affiliations
    Department of Plastic Surgery, Xijing Hospital, The Fourth Military Medical University, #15 Changlexilu, Xi’an City, Shaanxi Province 710032, China
    Search for articles by this author
  • S.Z. Guo
    Correspondence
    Corresponding author. Tel./fax: +86 029 83375301.
    Affiliations
    Department of Plastic Surgery, Xijing Hospital, The Fourth Military Medical University, #15 Changlexilu, Xi’an City, Shaanxi Province 710032, China
    Search for articles by this author

      Summary

      The objective of this study was to determine the effects of adenovirus-mediated vascular endothelial growth factor (Ad-VEGF) on the angiogenesis and survival of free-fat tissue transplantation in nude mice. Thirty 6-week-old CD-1 nude male mice were injected with 1 ml fat tissue (harvested by suction-assisted lipectomy from the breast of humans) in the subcutaneous of scalp and were randomised into three groups of 10 animals each. Group 1 was the study group, in which Ad-VEGF was mixed with transplanted fat tissue and injected into mice. In group 2, adenovirus-mediated green fluorescent protein (Ad-GFP) gene was mixed with transplanted fat tissue and injected into the mice. In group 3, normal saline alone was used. Both group 2 and group 3 are control groups. The animals were euthanised 15 weeks after the procedure. The fat survival weight and volume of the study group were significantly greater than those of two control groups (p<0.05). Light microscopical examination of haematoxylin and eosin-stained slides of the dissected fat 15 weeks after injection was performed in group 1 and group 2. Less cyst formation and fibrosis, indicating improved quality of the injected fat, can be obtained by the addition of Ad-VEGF. Vascular density was evaluated at the microvascular level through the use of light microscopic sections of the central part of the fat tissue at 15 weeks after injection by von Willebrand factor staining. Histological evaluation showed that capillary density increased markedly in the study group mice. Mice of the study group disclosed significantly higher VEGF protein levels detected by ELISA assay of plasma samples obtained from the mice after the fat injection (day 1, 4, 7 and 28; p<0.01) at each time point than the mice of the two control groups. The findings reported in this study indicate that the VEGF gene therapy can enhance the survival and the quality of grafted fat tissue, which may be due to induction of angiogenesis.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Plastic, Reconstructive & Aesthetic Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Chajchir A.
        Fat injection: long-term follow-up.
        Aesthetic Plast Surg. 1996; 20: 291-296
        • Rieck B.
        • Schlaak S.
        Measurement in vivo of the survival rate in autologous adipocyte transplantation.
        Plast Reconstr Surg. 2003; 111: 2315-2323
        • Langer S.
        • Sinitsina I.
        • Biberthaler P.
        • et al.
        Revascularization of transplanted adipose tissue: a study in the dorsal skinfold chamber of hamsters.
        Ann Plast Surg. 2002; 48: 53-59
        • Baran C.N.
        • Celebioglu S.
        • Sensoz O.
        • et al.
        The behavior of fat grafts in recipient areas with enhanced vascularity.
        Plast Reconstr Surg. 2002; 109 ([1652]): 1646-1651
        • Tepper O.M.
        • Galiano R.D.
        • Kalka C.
        • et al.
        Endothelial progenitor cells: the promise of vascular stem cells for plastic surgery.
        Plast Reconstr Surg. 2003; 111: 846-854
        • Gurunluoglu R.
        • Ozer K.
        • Skugor B.
        • et al.
        Effect of transfection time on the survival of epigastric skin flaps pretreated with adenovirus encoding the VEGF gene.
        Ann Plast Surg. 2002; 49: 161-169
        • Hazama K.
        • Nishibe T.
        • Shimada T.
        • et al.
        Effects of omental wrap on performance of small-caliber high-porosity expanded polytetrafluoroethylene grafts.
        J Surg Res. 1999; 81: 174-180
        • Yang L.W.
        • Zhang J.X.
        • Zeng L.
        • et al.
        Vascular endothelial growth factor gene therapy with intramuscular injections of plasmid DNA enhances the survival of random pattern flaps in a rat model.
        Br J Plast Surg. 2005; 58: 339-347
        • Katsube K.
        • Bishop A.T.
        • Simari R.D.
        • et al.
        Vascular endothelial growth factor (VEGF) gene transfer enhances surgical revascularization of necrotic bone.
        J Orthop Res. 2005; 23: 469-474
        • Liu P.Y.
        • Tong W.
        • Liu K.
        • et al.
        Liposome-mediated transfer of vascular endothelial growth factor cDNA augments survival of random-pattern skin flaps in the rat.
        Wound Repair Regen. 2004; 12: 80-85
        • Arsic N.
        • Zacchigna S.
        • Zentilin L.
        • et al.
        Vascular endothelial growth factor stimulates skeletal muscle regeneration in vivo.
        Mol Ther. 2004; 10: 844-854
        • Lubiatowski P.
        • Gurunluoglu R.
        • Goldman C.K.
        • et al.
        Gene therapy by adenovirus-mediated vascular endothelial growth factor and angiopoietin-1 promotes perfusion of muscle flaps.
        Plast Reconstr Surg. 2002; 110: 149-159
        • Yla-Herttuala S.
        • Martin J.F.
        Cardiovascular gene therapy.
        Lancet. 2000; 355: 213-222
        • Shoshani O.
        • Livne E.
        • Armoni M.
        • et al.
        The effect of interleukin-8 on the viability of injected adipose tissue in nude mice.
        Plast Reconstr Surg. 2005; 115: 853-859
        • Ullmann Y.
        • Hyams M.
        • Ramon Y.
        • et al.
        Enhancing the survival of aspirated human fat injected into nude mice.
        Plast Reconstr Surg. 1998; 101: 1940-1944
        • Shoshani O.
        • Ullmann Y.
        • Shupak A.
        • et al.
        The role of frozen storage in preserving adipose tissue obtained by suction-assisted lipectomy for repeated fat injection procedures.
        Dermatol Surg. 2001; 27: 645-647
        • Ramon Y.
        • Shoshani O.
        • Peled I.J.
        • et al.
        Enhancing the take of injected adipose tissue by a simple method for concentrating fat cells.
        Plast Reconstr Surg. 2005; 115 ([discussion 202–193]): 197-201
        • Shoshani O.
        • Shupak A.
        • Ullmann Y.
        • et al.
        The effect of hyperbaric oxygenation on the viability of human fat injected into nude mice.
        Plast Reconstr Surg. 2000; 106 ([discussion 1397–8]): 1390-1396
        • Park S.
        • Tepper O.M.
        • Galiano R.D.
        • et al.
        Selective recruitment of endothelial progenitor cells to ischemic tissues with increased neovascularization.
        Plast Reconstr Surg. 2004; 113: 284-293
        • Yuksel E.
        • Weinfeld A.B.
        • Cleek R.
        • et al.
        Increased free fat-graft survival with the long-term, local delivery of insulin, insulin-like growth factor-I, and basic fibroblast growth factor by PLGA/PEG microspheres.
        Plast Reconstr Surg. 2000; 105: 1712-1720
        • Ersek R.A.
        Transplantation of purified autologous fat: a 3-year follow-up is disappointing.
        Plast Reconstr Surg. 1991; 87 ([discussion 228]): 219-227
        • Illouz Y.G.
        Present results of fat injection.
        Aesthetic Plast Surg. 1988; 12: 175-181
        • Bartynski J.
        • Marion M.S.
        • Wang T.D.
        Histopathologic evaluation of adipose autografts in a rabbit ear model.
        Otolaryngol Head Neck Surg. 1990; 102: 314-321
        • Guerrerosantos J.
        • Gonzalez-Mendoza A.
        • Masmela Y.
        • et al.
        Long-term survival of free fat grafts in muscle: an experimental study in rats.
        Aesthetic Plast Surg. 1996; 20: 403-408
        • Billings Jr., E.
        • May Jr., J.W.
        Historical review and present status of free fat graft autotransplantation in plastic and reconstructive surgery.
        Plast Reconstr Surg. 1989; 83: 368-381
        • Mandrekas A.D.
        • Zambacos G.J.
        • Kittas C.
        Cyst formation after fat injection.
        Plast Reconstr Surg. 1998; 102: 1708-1709
        • Sommer B.
        • Sattler G.
        Current concepts of fat graft survival: histology of aspirated adipose tissue and review of the literature.
        Dermatol Surg. 2000; 26: 1159-1166
        • Nishimura T.
        • Hashimoto H.
        • Nakanishi I.
        • et al.
        Microvascular angiogenesis and apoptosis in the survival of free fat grafts.
        Laryngoscope. 2000; 110: 1333-1338