Effects of Insulin, Metoprolol and Deferoxamine on Fat Graft Survival

  • Mehmet Fatih Okyay
  • Hasan Kömürcü
  • Semih Bağhaki
  • Anıl Demiröz
  • Övgü Aydın
  • Hakan ArslanEmail author
Original Article Basic Science/Experimental



The main problem faced with fat grafting is unpredictable resorption rates. Many substances have been reported to increase the survival of fat grafts. The aim of this study was to compare the effects of insulin, metoprolol and deferoxamine on fat graft survival.


Inguinal fat pads of male Sprague–Dawley rats were harvested and split into four parts as grafts. The grafts were placed in subcutaneous pockets in four quadrants on the back area of the rats. The insulin and metoprolol group fat grafts were incubated in regular insulin and metoprolol solutions, until they were placed. Deferoxamine and control group fat grafts were placed without incubation. After surgery, the control group fat grafts were injected with 10 doses of NaCl solution once every 3 days, and the deferoxamine group fat grafts were injected with 10 doses of deferoxamine solution once every 3 days. After a graft maturation period of 3 months, the grafts were harvested for weight measurements and histological and immunohistochemical evaluation.


According to the rate of perilipin staining, the metoprolol group had 30% more mature viable adipocytes than the control and insulin group fat grafts (p < 0.05 and p < 0.01, respectively). CD31 activation rates were significantly higher in the deferoxamine and insulin group than in the metoprolol group (p < 0.05). CD34 staining rates did not differ between any groups (p > 0.05).


In this experimental study, we have shown that there was no significantly increased fat graft survival rate seen in any drug treatment group. Low survival rates of stem cells demonstrated that the adipogenesis period ended at 3 months. Treatment of fat grafts with the selective β1-blocker metoprolol resulted in good quality better graft take with more viable mature adipocytes. However, better viability of adipocytes did not result in increased weight of the fat graft. Studies aiming to compare the effects on fat graft survival of beta-blockers with long or short durations of action, different potencies and different receptor selectivity may be designed in the future. In addition, further studies may be performed, in which immunohistochemical markers used to assess inflammation and fibrosis are added to the study after the completion of the fat graft maturation period at the end of the first year to test the permanence of the results.

No Level Assigned

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors -


Fat graft Survival Metoprolol Deferoxamine Insulin 



This study was financially supported by the Istanbul University Scientific Research Projects Committee (Project ID: 24277).

Compliance with Ethical Standards

Conflict of interest

All authors report no conflicts of interest. No competing financial interests exist.

Ethical Approval

Ethical approval was obtained from the Experimental Animals Local Ethics Committee of Aziz Sancar Experimental Medical Research Institute of Istanbul University, and the experimental protocols for animal studies were adhered to throughout the study. All applicable institutional and/or national guidelines for the care and use of animals were followed.

Informed Consent

For this type of study, informed consent is not required.


  1. 1.
    Strong AL, Cederna PS, Rubin JP, Coleman SR, Levi B (2015) The Current state of fat grafting: a review of harvesting, processing, and injection techniques. Plast Reconstr Surg 136(4):897–912Google Scholar
  2. 2.
    Locke MB, De Chalain TMB, Plast F (2008) Current practice in autologous fat transplantation suggested clinical guidelines based on a review of recent literature. Ann Plast Surg 60(1):98–102Google Scholar
  3. 3.
    Xie Y, Zheng D, Li Q, Chen Y, Lei H, Pu LLQ (2010) The effect of centrifugation on viability of fat grafts: an evaluation with the glucose transport test. J Plast Reconstr Aesthet Surg 63(3):482–487Google Scholar
  4. 4.
    Yuksel E, Weinfeld AB, Cleek R, Wamsley S, Jensen J, Boutros S et al (2000) 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 105(5):1712–1720Google Scholar
  5. 5.
    Ayhan M, Şenen D, AdanalI G, Görgü M, Erdoǧan B, Albayrak B (2001) Use of beta blockers for increasing: survival of free fat grafts. Aesthet Plast Surg 25(5):338–342Google Scholar
  6. 6.
    Flacco J, Chung N, Blackshear CP, Irizarry D, Momeni A, Lee GK et al (2018) Deferoxamine preconditioning of irradiated tissue improves perfusion and fat graft retention. Plast Reconstr Surg 141(3):655–665Google Scholar
  7. 7.
    Temiz G, Sirinoglu H, Yesiloglu N, Filinte D, Kaçmaz C (2016) Effects of deferoxamine on fat graft survival. Facial Plast Surg 32(4):438–443Google Scholar
  8. 8.
    Fontdevila J, Guisantes E, Martinez E, Prades E, Berenguer J (2014) Double-blind clinical trial to compare autologous fat grafts versus autologous fat grafts with PDGF: no effect of PDGF. Plast Reconstr Surg 134(2):219e–230eGoogle Scholar
  9. 9.
    Luo S, Hao L, Li X, Yu D, Diao Z, Ren L et al (2013) Adipose tissue-derived stem cells treated with estradiol enhance survival of autologous fat transplants. Tohoku J Exp Med 231(2):101–110Google Scholar
  10. 10.
    Topcu A, Aydin OE, Ünlü M, Barutcu A, Atabey A (2012) Increasing the viability of fat grafts by vascular endothelial growth factor. Arch Facial Plast Surg 14(4):270–276Google Scholar
  11. 11.
    Smith P, Adams WP, Lipschitz AH, Chau B, Sorokin E, Rohrich RJ et al (2006) Autologous human fat grafting: effect of harvesting and preparation techniques on adipocyte graft survival. Plast Reconstr Surg 117(6):1836–1844Google Scholar
  12. 12.
    Ersek RA (1991) Transplantation of purified autologous Fat: a 3-year follow-up is disappointing. Plast Reconstr Surg 87(2):219–227Google Scholar
  13. 13.
    Fournier PF (2000) Fat grafting: my technique. Dermatol Surg 26(12):1117–1128Google Scholar
  14. 14.
    Mojallal A, Shipkov C, Braye F, Breton P, Foyatier JL (2009) Influence of the recipient site on the outcomes of fat grafting in facial reconstructive surgery. Plast Reconstr Surg 124(2):471–483Google Scholar
  15. 15.
    Agostini T, Lazzeri D, Pini A, Marino G, Li Quattrini A, Bani D et al (2010) Wet and dry techniques for structural fat graft harvesting: histomorphometric and cell viability assessments of lipoaspirated samples. Plast Reconstr Surg 130(2):331–339Google Scholar
  16. 16.
    Önel D, Emekli U, Çizmeci MO, Aköz F, Bilgiç B (2003) Review of fat grafting and the fate of the subperiostal fat graft. Eur J Plast Surg 26(4):169–174Google Scholar
  17. 17.
    Coleman SR (1997) Facial recontouring with lipostructure. Clin Plast Surg 24(2):34767Google Scholar
  18. 18.
    Zielins ER, Brett EA, Longaker MT, Wan DC (2016) Autologous fat grafting: the science behind the surgery. Aesthet Surg J 36(4):488–496Google Scholar
  19. 19.
    Zhao J, Yi C, Li L, Zheng Y, Wu K, Liang L et al (2012) Observations on the survival and neovascularization of fat grafts interchanged between C57BL/6-gfp and C57BL/6 mice. Plast Reconstr Surg 130(3):398–406Google Scholar
  20. 20.
    Phipps KD, Gebremeskel S, Gillis J, Hong P, Johnston B, Bezuhly M (2015) Alternatively activated M2 macrophages improve autologous fat graft survival in a mouse model through induction of angiogenesis. Plast Reconstr Surg 135(1):140–149Google Scholar
  21. 21.
    Soares MA, Ezeamuzie OC, Ham MJ, Duckworth AM, Rabbani PS, Saadeh PB et al (2015) Targeted protection of donor graft vasculature using a phosphodiesterase inhibitor increases survival and predictability of autologous fat grafts. Plast Reconstr Surg 135(2):488–499Google Scholar
  22. 22.
    Garza RM, Rennert RC, Paik KJ, Atashroo D, Chung MT, Duscher D et al (2015) Studies in fat grafting: part IV. Adipose-derived stromal cell gene expression in cell-assisted lipotransfer. Plast Reconstr Surg 135(4):1045–1055Google Scholar
  23. 23.
    Varghese J, Griffin M, Mosahebi A, Butler P (2017) Systematic review of patient factors affecting adipose stem cell viability and function: implications for regenerative therapy. Stem Cell Res Ther 8(1):45Google Scholar
  24. 24.
    Hao L, Luo S, Li X, Yu D, Diao Z, Ren L et al (2013) Estradiol enhanced survival ratio of fat transplant adipose tissue-derived stem cells treated with estradiol enhance survival of autologous fat transplants. Tohoku J Exp Med Tohoku J Exp Med. 231(2312):101–110Google Scholar
  25. 25.
    Hong L, Colpan A, Peptan IA (2006) Modulations of 17-β estradiol on osteogenic and adipogenic differentiations of human mesenchymal stem cells. Tissue Eng 12(10):2747–2753Google Scholar
  26. 26.
    D’Eon TM, Souza SC, Aronovitz M, Obin MS, Fried SK, Greenberg AS (2005) Estrogen regulation of adiposity and fuel partitioning: evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways. J Biol Chem 280(43):35983–35991Google Scholar
  27. 27.
    Boucher J, Kleinridders A, Ronald Kahn C (2014) Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb Perspect Biol 6(1):a009191Google Scholar
  28. 28.
    Witters LA, Watts TD, Daniels DL, Evans JL (1988) Insulin stimulates the dephosphorylation and activation of acetyl-CoA carboxylase. Proc Natl Acad Sci USA 85(15):5473–5477Google Scholar
  29. 29.
    Ramseyer VD, Granneman JG (2016) Adrenergic regulation of cellular plasticity in brown, beige/brite and white adipose tissues. Adipocyte 5(2):119–129Google Scholar
  30. 30.
    Eto H, Kato H, Suga H, Aoi N, Doi K, Kuno S et al (2012) The fate of adipocytes after nonvascularized fat grafting: evidence of early death and replacement of adipocytes. Plast Reconstr Surg 129(5):1081–1092Google Scholar
  31. 31.
    Suga H, Eto H, Aoi N, Kato H, Araki J, Doi K et al (2010) Adipose tissue remodeling under ischemia: death of adipocytes and activation of stem/progenitor cells. Plast Reconstr Surg 126(6):1911–1923Google Scholar
  32. 32.
    Sunaga A, Sugawara Y, Katsuragi-tomioka Y, Kobayashi E (2013) The fate of nonvascularized fat grafts: histological and bioluminescent study. Plast Reconstr Surg Glob Open 1(6):e41Google Scholar
  33. 33.
    Kato H, Mineda K, Eto H, Doi K, Kuno S, Kinoshita K et al (2014) Degeneration, regeneration, and cicatrization after fat grafting: dynamic total tissue remodeling during the first 3 months. Plast Reconstr Surg 133(3):303e–313eGoogle Scholar
  34. 34.
    Yoshimura K, Eto H, Kato H, Doi K, Aoi N (2011) Manipulation of stem cells for adipose tissue repair/reconstruction. Regen Med 6(6s):33–41Google Scholar
  35. 35.
    Raposio E, Caruana G, Petrella M, Bonomini S, Grieco MP (2016) A standardized method of isolating adipose-derived stem cells for clinical applications. Ann Plast Surg 76(1):124–126Google Scholar
  36. 36.
    Yoshimura K, Shigeura T, Matsumoto D, Sato T, Takaki Y, Aiba-Kojima E et al (2006) Characterization of freshly isolated and cultured cells derived from the fatty and fluid portions of liposuction aspirates. J Cell Physiol 208(1):64–76Google Scholar
  37. 37.
    Sengenès C, Lolmède K, Zakaroff-Girard A, Busse R, Bouloumié A (2005) Preadipocytes in the human subcutaneous adipose tissue display distinct features from the adult mesenchymal and hematopoietic stem cells. J Cell Physiol 205(1):114–122Google Scholar
  38. 38.
    Traktuev DO, Merfeld-Clauss S, Li J, Kolonin M, Arap W, Pasqualini R et al (2008) A population of multipotent CD34-positive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial networks. Circ Res 102(1):77–85Google Scholar
  39. 39.
    Lin G, Garcia M, Ning H, Banie L, Guo YL, Lue TF et al (2008) Defining stem and progenitor cells within adipose tissue. Stem Cells Dev 17(6):1053–1063Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery 2019

Authors and Affiliations

  1. 1.Plastic, Reconstructive and Aesthetic Surgery Department, Cerrahpaşa Medical Facultyİstanbul University – CerrahpaşaIstanbulTurkey
  2. 2.Pathology Department, Cerrahpaşa Medical Facultyİstanbul University – CerrahpaşaIstanbulTurkey

Personalised recommendations