Abstract
Background
Skin flap surgery is a cornerstone in plastic surgery. However, flaps may encounter postoperative partial or complete necrosis. Different modalities have been used to enhance skin flap survival. Adipose-derived stem cells (ASCs) can promote angiogenesis and improve skin flap survival. We aimed to investigate the appropriate timing of ASC administration to get the maximal angiogenic effect and better skin flap survival in rat model.
Methods
Thirty-two male albino Wistar rats were used to study the role of ASCs on caudally based (2 × 8 cm) random pattern skin flap survival; the 32 male albino rats were equally divided into four groups according to timing of ASC injection. We applied the ASCs at three different timing, group A (local injection of ASCs along the flap axis simultaneously with flap elevation), group B (2 days preoperatively), and group C (7 days preoperatively). In the control group (group D), the flap was injected with phosphate buffered saline at the time of flap elevation. Skin flap survival was evaluated on the seventh postoperative day through percentage of flap survival, capillary density, and vascular endothelial growth factor (VEGF) expression.
Results
ASCs led to a statistically significant increase in skin flap viability when administered simultaneously with flap elevation or 2 days prior to flap elevation. This went along with significant increase in capillary density and VEGF expression. However, the ASCs had no effect on flap survival when injected 1 week prior to flap elevation.
Conclusions
We demonstrate that the skin flap viability can be enhanced by local ASC administration simultaneously with flap elevation or 2 days prior to flap elevation. Their beneficial effect is attributed to paracrine secretion VEGF which enhanced the skin flap vascularity. The angiogenic effect of ASCs can be maximized when the ASCs are injected at the time of flap elevation.
Level of Evidence: Not ratable
Similar content being viewed by others
References
Lu F, Mizuno H, Uysal C et al (2008) Improved viability of random pattern skin flaps through the use of adipose-derived stem cells. Plast Reconstr Surg 121(1):50–58
Lubiatowski P, Goldman C, Gurunluoglu R et al (2002) Enhancement of epigastric skin flap survival by adenovirus-mediated VEGF gene therapy. Plast Reconstr Surg 109(6):1986–1993
Kuru B, Dinc S, Camlibel M et al (2003) Efficacy of postoperative steroids on ischemic skin flap survival in rats. Eur J Plast Surg 26(2):79–81
Engel H, Sauerbier M, Germann G et al (2007) Dose dependent effects of nitric oxide donor in a rat flap model. Ann Plast Surg 58(4):456–460
Haws M, Erdman D, Bayati S et al (2001) Basic fibroblast growth factor induced angiogenesis and prefabricated flap survival. J Reconstr Microsurg 17:39–42
Pang C, Lineaweaver W, Lei M et al (2003) Evaluation of the mechanism of vascular endothelial growth factor improvement of ischemic flap survival in rats. Plast Reconstr Surg 112(2):556–564
Qi Z, Gu Y, Kim D, Hiura A, Sumi S, Inoue K (2007) The effect of fibrin on the survival of ischemic skin flaps in rats. PlastReconstr Surg 120(5):1148–1455
Meirer R, Kamelger F, Huemer G et al (2005) Extracorporal shock wave may enhance skin flap survival in an animal model. Br J Plast Surg 58(1):53–57
Planat-Benard V, Silvestre J, Cousin B, André M, Nibbelink M, Tamarat R, Clergue M, Manneville C, Saillan-Barreau C, Duriez M, Tedgui A, Levy B, Pénicaud L, Casteilla L (2004) Plasticity of human adipose lineage cells toward endothelial cells. Circulation 109(5):656–663
Tang J, Xie Q, Pan G et al (2006) Mesenchymal stem cells participate in angiogenesis and improve heart function in rat model of myocardial ischemia with reperfusion. Eur J Cardiothorac Surg 30(2):353–361
Uyasl C, Ogawa R, Lu F et al (2010) Effect of mesenchymal stem cells on skin graft to flap prefabrication: an experimental study. Ann Plast Surg 65(2):237–244
Zhu M, Liu T, Song K et al (2008) Adipose-derived stem cell: a better stem cell than BMSC. Cell Biochem Funct 26:664–675
Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm-Grove CJ, Bovenkerk JE, Pell CL, Johnstone BH, Considine RV, March KL (2004) Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation 109(10):1292–1298
Keerl S, Gehmart S, Song Y et al (2010) PDGF and bFGF modulate tube formation in adipose tissue-derived stem cells. Ann Plast Surg 64(4):487–490
Yang M, Sheng L, Li H, Weng R, Li QF (2010) Improvement of the skin flap survival with the bone marrow-derived mononuclear cells transplantation in a rat model. Microsurgery 30(4):275–281
McFarlane R, Deyoung G, Henry R (1965) The design of a pedicle flap in the rat to study necrosis and its prevention. Plast Reconstr Surg 35(2):177–182
Simman R, Craft C, Mckinney B (2005) Improved survival of ischemic random skin flaps through the use of bone marrow non-hematopoietic stem cells and angiogenic growth factors. Ann Plast Surg 54(5):546–552
Gao W, Qiao X, Ma S, Cui L (2011) Adipose-derived stem cells accelerate neovascularization in ischaemic diabetic skin flap via expression ofhypoxia-inducible factor-1α. J Cell Mol Med 15(12):2575–2585
Karathanasis V, Petrakis S, Topouridou K, Koliakou E, Koliakos G, Demiri E (2013) Intradermal injection of GFP-producing adipose stromal cells promotes survival of random-pattern skin flaps in rats. Eur J Plast Surg 36(5):281–288
Suartz C, Gaiba S, França J et al (2014) Adipose-derived stem cells (ADSC) in the viability of a random pattern dorsal skin flap in rats. Acta Cir Bras 29(Suppl 3):2–5
Lee D, Jeon Y, Cho E et al (2014) Optimal administration routes for adipose derived stem cells therapy in ischaemic flaps. J Tissue Eng Regen Med 8(8):596–603
Cherubino M, Rubin J, Miljkovic N et al (2011) Adipose-derived stem cells for wound healing applications. Ann Plast Surg 66(2):210–215
Teng M, Huang Y, Zhang H (2014) Application of stems cells in wound healing—an update. Wound Repair Regen 22(2):151–160
Cao Y, Sun Z, Liao L, Meng Y, Han Q, Zhao RC (2005) Human adipose tissue-derived stem cells differentiate into endothelial cells invitro and improve postnatal neovascularization in vivo. Biochem Biophys Res Commun 332(2):370–379
Murohara T, Shintani S, Kondo K (2009) Autologous adipose-derived regenerative cells for therapeutic angiogenesis. Curr Pharm Des 15(24):2784–2790
Park I, Mondal A, Chung PS et al (2015) Prevention of skin flap necrosis by use of adipose derived stromal cells with light-emitting diode phototherapy. Cytotherapy 17(3):283–292
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
This research had not received any fund.
Conflict of interest
Ahmed Atef, Ayman Abu El Makarem Shaker, Eman Yahya Sadek, Nahed Samir Boughdadi, Suzi Sobhy Atalla, Fatma Abu Zahra declare that they have no conflict of interest.
Ethical approval
This research is approved by the Ethical Committee of Faculty of Medicine, Ain Shams University (Diary no. FMASU 982/2011). All applicable international guidelines and Faculty of Medicine, Ain Shams University guidelines for the care and use of animals were followed.
Rights and permissions
About this article
Cite this article
Atef, A., Shaker, A., Sadek, E.Y. et al. The optimal timing of adipose derived stem cells injection to improve skin flap survival in a rat model. Eur J Plast Surg 41, 387–394 (2018). https://doi.org/10.1007/s00238-018-1400-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00238-018-1400-9