title: Use of Adipose-Derived Mesenchymal Stem Cells to Accelerate Neovascularization in Interpolation Flaps.
abstract: OBJECTIVE
  Interpolation flaps are commonly used in plastic surgery to cover wide and deep defects. The need to, wait for 2 to 3 weeks until the division of the pedicle still, however, poses a serious challenge, not only extending treatment and hospital stay, but also increasing hospital expenses. To solve this problem, we have aimed to use the angiogenic potential of stem cells to selectively accelerate neovascularization with a view to increasing the viability of interpolation flaps and achieving early pedicle removal.
  
  
  METHODS
  A total of 32 rats were allocated to 2 groups as control (N = 16) and experiment (N = 16). The cranial flaps 6 × 5 cm in size located on the back of the rats were raised. Then, a total suspension containing 3 × 10(6) adipose-derived mesenchymal stem cells (ADSC) tagged with a green fluorescent protein (GFP) was injected diffusely into the distal part of the flap, receiving bed, and wound edges. In the control group, only a medium solution was injected into the same sites. After covering the 3 × 5 cm region in the proximal part of the area where the flap was removed, the distal part of the flap was adapted to the uncovered distal area. The pedicles of 4 rats in each group were divided on postoperative days 5, 8, 11, and 14. The areas were photographed 7 days after the pedicles were released. The photographs were processed using Adobe Acrobat 9 Pro software (San Jose, CA) to measure the flap survival area in millimeters and to compare groups. Seven days after the flap pedicle was divided, the rats were injected with 250 mCi Tc-99 mm (methoxy-isobutyl-isonitrie) from the penile vein, and scintigraphic images were obtained. The images obtained from each group were subjected to a numerical evaluation, which was then used in the comparison between groups. The flaps were then examined by histology to numerically compare the number of newly formed vessels. Neovascularization was also assessed by microangiography. In addition, radiographic images were obtained by mammography and evaluated quantitatively.
  
  
  RESULTS
  An evaluation of statistical results revealed a significant increase in the flap survival area of the group on stem cell treatment in comparison to the control group. In scintigraphic examinations, the rate of radioactive substance retention was significantly higher in the stem cell group, relative to the control group. Histopathologic examination showed that the capillary density in the stem cell group was higher than that in the control group. Green fluorescent protein had been used to label ADSC in the experiment and it was found by immunofluorescence staining that endothelial samples of control animals did not have GFP (+) cells, whereas all the animals in the experiment group had GFP (+) cells. The comparison of microangiographic images of the experiment and control groups demonstrated significantly elevated vascularity in the former, relative to the latter.
  
  
  CONCLUSIONS
  It has been established in the current study that ADSC injection worked well in speeding up the neovascularization of interpolated flaps and reducing the time of pedicle division. It seems possible to minimize the morbidity of interpolated skin flaps with mesenchymal stem cell therapy at an appropriate dose and for an appropriate length of time.
authors.affiliation: *Department of Plastic, Reconstructive and Aesthetic Surgery, Derince Training and Research Hospital †Department of Plastic, Reconstructive and Aesthetic Surgery, Kocaeli University, Faculty of Medicine, Kocaeli ‡Department of Plastic, Reconstructive and Aesthetic Surgery, Dumlupinar University, Evliya Celebi Training and Research Hospital, Kutahya §Center for Stem Cell and Gene Therapies Research and Practice, Kocaeli University ||Department of Nuclear Medicine ¶Department of Pathology, Kocaeli University, Faculty of Medicine, Kocaeli #Center for Regenerative Medicine and Stem Cell Research and Manufacturing, Liv Hospital, Istanbul, Turkey.
authors.forename: Hakki Hayrettin
authors.initials: HH
authors.lastname: Izmirli
authors.forename: Murat Sahin
authors.initials: MS
authors.lastname: Alagoz
authors.forename: Huseyin
authors.initials: H
authors.lastname: Gercek
authors.forename: Guler Gamze
authors.initials: GG
authors.lastname: Eren
authors.forename: Ergin
authors.initials: E
authors.lastname: Yucel
authors.forename: Cansu
authors.initials: C
authors.lastname: Subasi
authors.forename: Serkan
authors.initials: S
authors.lastname: Isgoren
authors.forename: Bahar
authors.initials: B
authors.lastname: Muezzinoglu
authors.forename: Erdal
authors.initials: E
authors.lastname: Karaoz
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000792:Angiography / Q000379:methods; D000818:Animals; D002196:Capillaries / Q000473:pathology; D018929:Cell Culture Techniques; D002469:Cell Separation; D005455:Fluorescent Antibody Technique; D006085:Graft Survival; D049452:Green Fluorescent Proteins; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008852:Microradiography / Q000379:methods; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010781:Photography / Q000379:methods; D019275:Radiopharmaceuticals; D051381:Rats; D017208:Rats, Wistar; D016038:Skin Transplantation / Q000379:methods*; D013524:Surgical Flaps / Q000098:blood supply / Q000637:transplantation*; D017256:Technetium Tc 99m Sestamibi
chemical_list: D019275:Radiopharmaceuticals; D049452:Green Fluorescent Proteins; D017256:Technetium Tc 99m Sestamibi