RSS-Feed abonnieren
DOI: 10.1055/s-0038-1648246
Adipose-Derived Stem Cells Ameliorate Ischemia-Reperfusion Injury in a Rat Skin Free Flap Model
Publikationsverlauf
15. Januar 2018
22. März 2018
Publikationsdatum:
03. Mai 2018 (online)
![](https://www.thieme-connect.de/media/jrm/201808/lookinside/thumbnails/10-1055-s-0038-1648246_170404-1.jpg)
Abstract
Background Ischemia-reperfusion (I/R) injury is inevitable during free tissue transfers. When the period of ischemia exceeds the tissue tolerance, it causes necrosis and flap failure. The aim of this study was to investigate the effects of adipose-derived stem cells (ASCs) embedded in a collagen type I scaffold on the survival of free skin flaps to counteract I/R injury.
Methods Left superficial caudal epigastric skin flaps (3 × 6 cm) were performed in 28 Wistar rats that were divided into four groups. The flaps elevated in the animals of the control group did not suffer any ischemic insult, and the vascular pedicle was not cut. All other flaps were subjected to 8 hours of ischemia prior to revascularization: I/R control group (8 hours of ischemia), I/R scaffold group (8 hours of ischemia + collagen type I scaffold), and I/R scaffold–ASCs group (8 hours of ischemia + collagen type I scaffold with rat ASCs embedded). Transit-time ultrasound blood flow measurements were performed. After 7 days, the areas of flap survival were measured and tissues were stained with hematoxylin/eosin and Masson's trichrome stain for histological analysis.
Results The mean percentage flap survival area was significantly higher in the ASCs-treated flaps (I/R scaffold–ASCs group) compared with the ischemic controls (I/R control group and I/R scaffold group). Higher vascular proliferation and lower severity of necrosis and inflammatory changes were seen histologically in the samples of the ASCs-treated group. No significant difference in blood flow was detected between groups.
Conclusion Subcutaneous administration of ASCs embedded on a collagen type I scaffold reduces tissue damage after I/R injury in microvascular free flaps.
-
References
- 1 Siemionow M, Arslan E. Ischemia/reperfusion injury: a review in relation to free tissue transfers. Microsurgery 2004; 24 (06) 468-475
- 2 Wang WZ, Baynosa RC, Zamboni WA. Update on ischemia-reperfusion injury for the plastic surgeon: 2011. Plast Reconstr Surg 2011; 128 (06) 685e-692e
- 3 Carroll WR, Esclamado RM. Ischemia/reperfusion injury in microvascular surgery. Head Neck 2000; 22 (07) 700-713
- 4 Harder Y, Amon M, Schramm R. , et al. Ischemia-induced up-regulation of heme oxygenase-1 protects from apoptotic cell death and tissue necrosis. J Surg Res 2008; 150 (02) 293-303
- 5 van den Heuvel MG, Buurman WA, Bast A, van der Hulst RR. Review: Ischaemia-reperfusion injury in flap surgery. J Plast Reconstr Aesthet Surg 2009; 62 (06) 721-726
- 6 Cetin C, Köse AA, Aral E. , et al. Protective effect of fucoidin (a neutrophil rolling inhibitor) on ischemia reperfusion injury: experimental study in rat epigastric island flaps. Ann Plast Surg 2001; 47 (05) 540-546
- 7 Han HH, Lim YM, Park SW, Lee SJ, Rhie JW, Lee JH. Improved skin flap survival in venous ischemia-reperfusion injury with the use of adipose-derived stem cells. Microsurgery 2015; 35 (08) 645-652
- 8 Wang WZ, Fang XH, Stephenson LL, Zhang X, Khiabani KT, Zamboni WA. Melatonin attenuates I/R-induced mitochondrial dysfunction in skeletal muscle. J Surg Res 2011; 171 (01) 108-113
- 9 Wang WZ. Investigation of reperfusion injury and ischemic preconditioning in microsurgery. Microsurgery 2009; 29 (01) 72-79
- 10 Tapuria N, Kumar Y, Habib MM, Abu Amara M, Seifalian AM, Davidson BR. Remote ischemic preconditioning: a novel protective method from ischemia reperfusion injury--a review. J Surg Res 2008; 150 (02) 304-330
- 11 Küntscher MV, Hartmann B, Germann G. Remote ischemic preconditioning of flaps: a review. Microsurgery 2005; 25 (04) 346-352
- 12 Park JW, Kang JW, Jeon WJ, Na HS. Postconditioning protects skeletal muscle from ischemia-reperfusion injury. Microsurgery 2010; 30 (03) 223-229
- 13 Bolcal C, Yildirim V, Doganci S. , et al. Protective effects of antioxidant medications on limb ischemia reperfusion injury. J Surg Res 2007; 139 (02) 274-279
- 14 Gravvanis A, Papalois A, Delikonstantinou I. , et al. Changes in arterial blood flow of free flaps after the administration of sildenafil in swine. Microsurgery 2011; 31 (06) 465-471
- 15 Fries CA, Villamaria CY, Spencer JR, Rasmussen TE, Davis MR. C1 esterase inhibitor ameliorates ischemia reperfusion injury in a swine musculocutaneous flap model. Microsurgery 2017; 37 (02) 142-147
- 16 Wang WZ, Fang XH, Stephenson LL. , et al. Nitrite attenuates ischemia-reperfusion-induced microcirculatory alterations and mitochondrial dysfunction in the microvasculature of skeletal muscle. Plast Reconstr Surg 2011; 128 (04) 279e-287e
- 17 Hong JP, Kwon H, Chung YK, Jung SH. The effect of hyperbaric oxygen on ischemia-reperfusion injury: an experimental study in a rat musculocutaneous flap. Ann Plast Surg 2003; 51 (05) 478-487
- 18 Eskitascioglu T, Karaci S, Canoz O, Kılıc E, Gunay GK. The impact of lidocaine on flap survival following reperfusion injury. J Surg Res 2011; 167 (02) 323-328
- 19 Fowler JD, Li X, Cooley BC. Brief ex vivo perfusion with heparinized and/or citrated whole blood enhances tolerance of free muscle flaps to prolonged ischemia. Microsurgery 1999; 19 (03) 135-140
- 20 Yin Z, Ren H, Liu L. , et al. Thioredoxin protects skin flaps from ischemia-reperfusion injury: a novel prognostic and therapeutic target. Plast Reconstr Surg 2016; 137 (02) 511-521
- 21 Reichenberger MA, Heimer S, Schaefer A. , et al. Adipose derived stem cells protect skin flaps against ischemia-reperfusion injury. Stem Cell Rev 2012; 8 (03) 854-862
- 22 Leng X, Fan Y, Wang Y. , et al. Treatment of ischemia-reperfusion injury of the skin flap using human umbilical cord mesenchymal stem cells (hUC-MSCs) transfected with “F-5” gene. Med Sci Monit 2017; 23: 2751-2764
- 23 Lasso JM, Del Río M, García M. , et al. Improving flap survival by transplantation of a VEGF-secreting endothelised scaffold during distal pedicle flap creation. J Plast Reconstr Aesthet Surg 2007; 60 (03) 279-286
- 24 Akimoto M, Takeda A, Matsushita O. , et al. Effects of CB-VEGF-A injection in rat flap models for improved survival. Plast Reconstr Surg 2013; 131 (04) 717-725
- 25 Li W, Enomoto M, Ukegawa M. , et al. Subcutaneous injections of platelet-rich plasma into skin flaps modulate proangiogenic gene expression and improve survival rates. Plast Reconstr Surg 2012; 129 (04) 858-866
- 26 Huang P, Tian X, Li Q, Yang Y. New strategies for improving stem cell therapy in ischemic heart disease. Heart Fail Rev 2016; 21 (06) 737-752
- 27 Hsiao LC, Carr C, Chang KC, Lin SZ, Clarke K. Stem cell-based therapy for ischemic heart disease. Cell Transplant 2013; 22 (04) 663-675
- 28 Rajan N, Habermehl J, Coté MF, Doillon CJ, Mantovani D. Preparation of ready-to-use, storable and reconstituted type I collagen from rat tail tendon for tissue engineering applications. Nat Protoc 2006; 1 (06) 2753-2758
- 29 Kochi T, Imai Y, Takeda A. , et al. Characterization of the arterial anatomy of the murine hindlimb: functional role in the design and understanding of ischemia models. PLoS One 2013; 8 (12) e84047
- 30 Wang Y, Orbay H, Huang C. , et al. Preclinical efficacy of slow-release bFGF in ischemia-reperfusion injury in a Dorsal Island skin flap model. J Reconstr Microsurg 2013; 29 (05) 341-346
- 31 Chafin B, Belmont MJ, Quraishi H, Clovis N, Wax MK. Effect of clamp versus anastomotic-induced ischemia on critical ischemic time and survival of rat epigastric fasciocutaneous flap. Head Neck 1999; 21 (03) 198-203
- 32 Finseth F, Cutting C. An experimental neurovascular island skin flap for the study of the delay phenomenon. Plast Reconstr Surg 1978; 61 (03) 412-420
- 33 Ozcan G, Shenaq S, Spira M. A new flap model in the rat. Ann Plast Surg 1991; 27 (04) 332-338
- 34 Deheng C, Kailiang Z, Weidong W. , et al. Salidroside promotes random skin flap survival in rats by enhancing angiogenesis and inhibiting apoptosis. J Reconstr Microsurg 2016; 32 (08) 580-586
- 35 Krag C, Holck S. The value of the patency test in microvascular anastomosis: correlation between observed patency and size of intraluminal thrombus: an experimental study in rats. Br J Plast Surg 1981; 34 (01) 64-66
- 36 Pafitanis G, Raveendran M, Myers S, Ghanem AM. Flowmetry evolution in microvascular surgery: a systematic review. J Plast Reconstr Aesthet Surg 2017; 70 (09) 1242-1251
- 37 Selber JC, Garvey PB, Clemens MW, Chang EI, Zhang H, Hanasono MM. A prospective study of transit-time flow volume measurement for intraoperative evaluation and optimization of free flaps. Plast Reconstr Surg 2013; 131 (02) 270-281
- 38 Shaughness G, Blackburn C, Ballestín A, Akelina Y, Ascherman JA. Predicting thrombosis formation in 1-mm-diameter arterial anastomoses with transit-time ultrasound technology. Plast Reconstr Surg 2017; 139 (06) 1400-1405
- 39 Archambault J, Moreira A, McDaniel D, Winter L, Sun L, Hornsby P. Therapeutic potential of mesenchymal stromal cells for hypoxic ischemic encephalopathy: a systematic review and meta-analysis of preclinical studies. PLoS One 2017; 12 (12) e0189895
- 40 Liu YY, Chiang CH, Hung SC. , et al. Hypoxia-preconditioned mesenchymal stem cells ameliorate ischemia/reperfusion-induced lung injury. PLoS One 2017; 12 (11) e0187637
- 41 Zhang JB, Wang XQ, Lu GL, Huang HS, Xu SY. Adipose-derived mesenchymal stem cells therapy for acute kidney injury induced by ischemia-reperfusion in a rat model. Clin Exp Pharmacol Physiol 2017; 44 (12) 1232-1240
- 42 Saidi RF, Rajeshkumar B, Shariftabrizi A. , et al. Human adipose-derived mesenchymal stem cells attenuate liver ischemia-reperfusion injury and promote liver regeneration. Surgery 2014; 156 (05) 1225-1231
- 43 Rigotti G, Marchi A, Sbarbati A. Adipose-derived mesenchymal stem cells: past, present, and future. Aesthetic Plast Surg 2009; 33 (03) 271-273
- 44 Ichioka S, Kudo S, Shibata M, Ando J, Sekiya N, Nakatsuka T. Bone marrow cell implantation improves flap viability after ischemia-reperfusion injury. Ann Plast Surg 2004; 52 (04) 414-418
- 45 Uysal AC, Mizuno H, Tobita M, Ogawa R, Hyakusoku H. The effect of adipose-derived stem cells on ischemia-reperfusion injury: immunohistochemical and ultrastructural evaluation. Plast Reconstr Surg 2009; 124 (03) 804-815
- 46 Amir Inbal MS, Kalchenko V, Kuznetsov Y. , et al. Targeted delivery of adipose derived stem cells into a transplant by direct intra-arterial administration. J Stem Cell Res Ther 2016; 6 (11) 1000367
- 47 Hara M, Murakami T, Kobayashi E. In vivo bioimaging using photogenic rats: fate of injected bone marrow-derived mesenchymal stromal cells. J Autoimmun 2008; 30 (03) 163-171
- 48 Delle Monache S, Calgani A, Sanità P. , et al. Adipose-derived stem cells sustain prolonged angiogenesis through leptin secretion. Growth Factors 2016; 34 (3-4): 87-96
- 49 Kang T, Jones TM, Naddell C. , et al. Adipose-derived stem cells induce angiogenesis via microvesicle transport of miRNA-31. Stem Cells Transl Med 2016; 5 (04) 440-450
- 50 Patrikoski M, Sivula J, Huhtala H. , et al. Different culture conditions modulate the immunological properties of adipose stem cells. Stem Cells Transl Med 2014; 3 (10) 1220-1230