Advertisement

Activation of mitosis and angiogenesis in diabetes-impaired wound healing by processed human amniotic fluid

Published:January 31, 2014DOI:https://doi.org/10.1016/j.jss.2014.01.041

      Abstract

      Background

      Functional characterization of human amniotic fluid (AF) proteome, 845 proteins, has revealed that top three functions are cell proliferation, movement and differentiation, events fundamental to development, and tissue repair. Although these findings fortify the idea that AF components play roles in regeneration-like fetal wound healing, it is not known whether the components endure processing. Therefore, we processed AF and tested its effects on diabetes-impaired wound healing in an animal model.

      Materials and methods

      Through a germfree procedure, mature and premature AF samples were collected, respectively, from the mothers of full-term and preterm infants. Excisional wounds were generated on the dorsum of diabetic rats. Wounds were treated on day 3 and harvested on day 7 postwounding. Proliferating cell nuclear antigen and alpha–smooth muscles actin, markers for mitosis and angiogenesis, respectively, were assessed by in situ immunodetection method.

      Results

      Significant increases in the rate of wound closure and proliferating cell nuclear antigen–expressing cells were observed in AF-treated wounds when compared with that of sham and control wounds. Likewise, the number of large vessels was significantly increased in the wounds treated with the AF. However, population of myofibroblasts was not affected by the treatment. The mature and premature AF were almost equally effective.

      Conclusions

      Our data, for the first time, show that processed AF accelerates diabetes-impaired wound healing by activating mitosis and angiogenesis, indicating that bioactive molecules in AF may endure processing. We believe that processed forms of this naturally designed “Cocktail” of bioactive molecules may have multiple clinical applications.

      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 Surgical Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Underwood M.A.
        • Gilbert W.M.
        • Sherman M.P.
        Amniotic fluid: not just fetal urine anymore.
        J Perinatolo. 2005; 25: 341
        • Cho C.K.
        • Shan S.J.
        • Winsor E.J.
        • Diamandis E.P.
        Proteomics analysis of human amniotic fluid.
        Mol cell Proteome. 2007; 6: 1406
        • Nilsson S.
        • Ramstrom M.
        • Palmblad M.
        • Axelsson O.
        • Bergguist J.
        Explorative study of the protein composition of amniotic fluid by liquid chromatography electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry.
        J Proteome Res. 2004; 3: 884
        • Park S.J.
        • Yoon W.G.
        • Song J.S.
        • et al.
        Proteome analysis of human amnion and amniotic fluid by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
        Proteomics. 2006; 6: 349
        • Clark R.A.F.
        Wound repair: overview and general considerations.
        in: Clark R.A.F. The Molecular and cellular biology of wound repair. Plenum Press, NewYork1996: 3-50
        • Gurtner G.C.
        • Werner S.
        • Barrandon Y.
        • Longaker M.T.
        Wound repair and regeneration.
        Nature. 2008; 453: 314
        • Midwood K.S.
        • Williams L.V.
        • Schwarzbauer J.E.
        Tissue repair and dynamics of the extracellular matrix.
        Int J Bioch Cell Biol. 2004; 36: 1031
        • Bullard K.M.
        • Longaker M.T.
        • Lorenz H.P.
        Fetal wound healing: current biology.
        World J Surg. 2003; 27: 54
        • Ferguson M.W.
        • O'Kane S.
        Scar-free healing: from embryonic mechanisms to adult therapeutic intervention.
        Philos Trans R Soc Lond B Biol Sci. 2004; 359: 839
        • Hirai C.
        • Ichiba H.
        • Saito M.
        • Shintaku H.
        • Yamano T.
        • Kusuda S.
        Trophic effect of multiple growth factors in amniotic fluid or human milk on cultured human fetal small intestinal cells.
        J Pediatr Gastroenterol Nutr. 2002; 34: 524
        • Bennett N.T.
        • Schultz G.S.
        Growth factors and wound healing: Part II. Role in normal and chronic wound healing.
        Am J Surg. 1993; 166: 74
        • Montesano R.
        • Orci L.
        Transforming growth factor beta stimulates collagen-matrix contraction by fibroblasts: implications for wound healing.
        Proc Natl Acad Sci. 1988; 85: 4894
        • Varedi M.
        • Tabei Z.A.
        • Dehghani Gholam Abbas
        • Tabei Sayed Ziaedin
        Local administration of L-arginine accelerates wound closure.
        IJBMS. 2009; 12: 173
        • Debats I.B.
        • Wolfs T.G.
        • Gotoh T.
        • Cleutjens J.P.
        • Peutz-Kootstra C.J.
        • van der Hulst R.R.
        Role of arginine in superficial wound healing in man.
        Nitric Oxide. 2009; 21: 175
        • Igarashi K.
        • Kashiwagi K.
        Modulation of cellular function by polyamines.
        Int J Biochem Cell Biol. 2010; 42: 39
        • Kwon H.
        • Wu G.
        • Bazer F.W.
        • Spencer T.E.
        Developmental changes in polyamine levels and synthesis in the ovine conceptus.
        Biolo Repro. 2003; 69: 1626
        • Kerimoglu S.
        • Livaoglu M.
        • Sonmez B.
        • et al.
        Effects of human amniotic fluid on fracture healing in rat tibia.
        J Surg Res. 2009; 152: 281
        • Ozgenel G.Y.
        • Samli B.
        • Ozcan M.
        Effects of human amniotic fluid on peritendinous adhesion formation and tendon healing after flexor tendon surgery in rabbits.
        J Hand Surg Am. 2001; 26: 332
        • Ozgenel G.Y.
        • Filiz G.
        Effects of human amniotic fluid on peripheral nerve scarring and regeneration in rats.
        J Neuro Surg. 2003; 98: 371
        • Karacal N.
        • Kosucu P.
        • Cobanglu U.
        • Kutlu N.
        Effect of human amniotic fluid on bone healing.
        J Surg Res. 2005; 129: 283
        • Esmaeili A.
        • Abbasian B.
        • Kazemini H.
        • Adibi S.
        Effect of bovine amniotic fluid on intra-abdominal adhesion in male rats.
        Int J Surg. 2010; 8: 639
        • Burtis C.A.
        • Ashwood E.R.
        Tietz textbook of clinical chemistry.
        W.B Saunders Company, Philadelphia1994
        • Sambrook J.
        • Fritsch E.F.
        • Maniatis T.
        Molecular cloning a laboratory manual.
        Cold Spring Harbor Laboratory Press, New York1989
        • Varedi M.
        • Englander E.
        TGF-ß1 latency associated peptide promotes remodeling of cutaneous healing wounds.
        IJMS. 2006; 31: 65
        • Sanders E.J.
        • Varedi M.
        • French A.S.
        Cell proliferation in the gastrulating chick embryo: a study using BrdU incorporation and PCNA localization.
        Development. 1993; 118: 389
        • Brem H.
        • Tomic-Canic M.
        Cellular and molecular basis of wound healing in diabetes.
        J Clin Invest. 2007; 117: 1219
        • Lerman O.Z.
        • Galiano R.D.
        • Armour M.
        • Levine J.P.
        • Gurtner G.C.
        Cellular dysfunction in the diabetic fibroblast: impairment in migration, vascular endothelial growth factor production, and response to hypoxia.
        Am J Pathol. 2003; 162: 303
        • Tsuboi R.
        • Rifkin D.B.
        Recombinant basic fibroblast growth factor stimulates wound healing in healing-impaired db/db mice.
        J Exp Med. 1990; 172: 245
        • Kopp J.
        • Wang G.Y.
        • Kulmburg P.
        • et al.
        Accelerated wound healing by in vivo application of keratinocytes overexpressing KGF.
        Mol ther J Am Soci Gene Therap. 2004; 10: 86
        • Chrissouli S.
        • Pratsinis H.
        • Velissariou V.
        • Anastasiou A.
        • Kletsas D.
        Human amniotic fluid stimulates the proliferation of human fetal and adult skin fibroblasts: the roles of bFGF and PDGF and of the ERK and Akt signaling pathways.
        Wound Repair Regen. 2010; 18: 643
        • Brown R.L.
        • Breeden M.P.
        • Greenhalgh D.G.
        PDGF and TGF-alpha act synergistically to improve wound healing in the genetically diabetic mouse.
        J Surg Res. 1994; 56: 562
        • Greenhalgh D.G.
        • Sprugel K.H.
        • Murry M.J.
        • Ross R.
        PDGF and FGF stimulate wound healing in the genetically diabetic mouse.
        Am J Pathol. 1990; 136: 1235