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A Prospective Study of 20 Foot and Ankle Wounds Treated with Cryopreserved Amniotic Membrane and Fluid Allograft

      Abstract

      We reviewed the background information and previous clinical studies that considered the use of allogeneic amniotic tissue and fluid (granulized amniotic membrane and amniotic fluid) in the treatment of chronic diabetic foot wounds. This innovation represents a relatively new approach to wound management by delivering a unique allograft of live human cells in a nonimmunogenic structural tissue matrix. Developed to fill soft tissue defects and bone voids and to convey antimicrobial and anti-inflammatory capabilities, granulized amniotic membrane and amniotic fluid does not require fetal death, because its procurement is performed with maternal consent during birth. In the present investigation, 20 chronic wounds (20 patients) that had been treated with standard wound therapy for a mean of 36.6 ± 31.58 weeks and with a mean baseline area of 10.15 ± 19.54 cm2 were followed up during a 12-week observation period or until they healed. A total of 18 of the wounds (90%) healed during the 12-week observation period, and none of the wounds progressed to amputation. From our experience with the patients in the present case series, we believe that granulized amniotic membrane and amniotic fluid represents a useful option for the treatment of chronic diabetic foot wounds.

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      References

        • Scheubel R.J.
        • Zorn H.
        • Silber R.E.
        • Kuss O.
        • Morawietz H.
        • Holtz J.
        • Simm A.
        Age-dependent depression in circulating endothelial progenitor cells in patients undergoing coronary artery bypass grafting.
        J Am Coll Cardiol. 2003; 42: 2073-2080
        • Sakuragawa N.
        • Kakinuma K.
        • Kikuchi A.
        • Okano H.
        • Uchida S.
        • Kamo I.
        • Kobayashi M.
        • Yokoyama Y.
        Human amnion mesenchyme cells express phenotypes of neuroglial progenitor cells.
        J Neurosci Res. 2004; 78: 208-214
        • Horwitz E.M.
        • Le Blanc K.
        • Dominici M.
        • Mueller I.
        • Slaper-Cortenbach I.
        • Marini F.C.
        • Deans R.J.
        • Krause D.S.
        • Keating A.
        Clarification of the nomenclature for MSC: the International Society for Cellular Therapy position statement.
        Cytotherapy. 2005; 7: 393-395
        • Modesti A.
        • Scarpa S.
        • D'Orazi G.
        • Simonelli L.
        • Caramia F.G.
        Localization of type IV and V collagens in the stroma of human amnion.
        Progr Clin Biol Res. 1989; 296: 459-463
        • Fukuda K.
        • Chikama T.
        • Nakamura M.
        • Nishida T.
        Differential distribution of subchains of the basement membrane components type IV collagen and laminin among the amniotic membrane, cornea, and conjunctiva.
        Cornea. 1999; 18: 73-79
        • Koizumi N.J.
        • Inatomi T.J.
        • Sotozono C.J.
        • Fullwood N.J.
        • Quantock A.J.
        • Kinoshita S.
        Growth factor mRNA and protein in preserved human amniotic membrane.
        Curr Eye Res. 2000; 20: 173-177
        • Trelford J.D.
        • Trelford-Sauder M.
        The amnion in surgery, past and present.
        Am J Obstet Gynecol. 1979; 134: 833-845
        • Colocho G.
        • Graham III, W.P.
        • Greene A.E.
        • Matheson D.W.
        • Lynch D.
        Human amniotic membrane as a physiologic wound dressing.
        Arch Surg. 1974; 109: 370-373
        • Prasad J.K.
        • Feller I.
        • Thomson P.D.
        Use of amnion for the treatment of Stevens-Johnson syndrome.
        J Trauma. 1986; 26: 945-946
        • Subrahmanyam M.
        Amniotic membrane as a cover for microskin grafts.
        Br J Plast Surg. 1995; 48: 477-478
        • Cheung C.Y.
        Vascular endothelial growth factor activation of intramembranous absorption: a critical pathway for amniotic fluid volume regulation.
        J Soc Gynecol Investig. 2004; 11: 63-74
        • Moshiri A.
        • Oryan A.
        Structural and functional modulation of early healing of full-thickness superficial digital flexor tendon rupture in rabbits by repeated subcutaneous administration of exogenous human recombinant basic fibroblast growth factor.
        J Foot Ankle Surg. 2011; 50: 654-662
        • Yoshio H.
        • Tollin M.
        • Gudmundsson G.H.
        Antimicrobial polypeptides of human vernix caseosa and amniotic fluid: implications for newborn innate defense.
        Pediatr Res. 2003; 53: 211-216
        • Espinoza J.
        • Chaiworapongsa T.
        • Romero R.
        Antimicrobial peptides in amniotic fluid: defensins, calprotectin and bacterial/permeability-increasing protein in patients with microbial invasion of the amniotic cavity, intra-amniotic inflammation, preterm labor and premature rupture of membranes.
        J Matern Fetal Neonatal Med. 2003; 13: 2-21
        • Akinbi H.T.
        • Narendran V.
        • Pass A.K.
        • Markart P.
        • Hoath S.B.
        Host defense proteins in vernix caseosa and amniotic fluid.
        Am J Obstet Gynecol. 2004; 191: 2090-2096
        • Otsuki K.
        • Yoda A.
        • Saito H.
        • Mitsuhashi Y.
        • Shimizu Y.
        • Yanaiha T.
        Amniotic fluid lactoferrin in intrauterine infection.
        Placenta. 1999; 20: 175-179
        • Ozgenel G.Y.
        • Filiz G.
        Effects of human amniotic fluid on peripheral nerve scarring and regeneration in rats.
        J Neurosurg. 2003; 98: 371-377
        • Gao X.
        • Devoe L.D.
        • Given K.S.
        Effects of amniotic fluid on proteases: a possible role of amniotic fluid in fetal wound healing.
        Ann Plast Surg. 1994; 33 (discussion 134–135): 128-134
        • Tsai M.S.
        • Lee J.L.
        • Chang Y.J.
        • Hwang S.M.
        Isolation of human multipotent mesenchymal stem cells from second trimester amniotic fluid using a novel two-stage culture protocol.
        Hum Reprod. 2004; 19: 1450-1456
        • In't Anker P.S.
        • Scherjon S.A.
        • Kleijburg-van der Keur C.
        • de Groot-Swings G.M.
        • Claas F.H.
        • Fibbe W.E.
        • Kanhai H.H.
        Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta.
        Stem Cells. 2004; 22: 1338-1345
        • Heil M.
        • Eitenmüller I.
        • Schmitz-Rixen T.
        • Schaper W.
        Arteriogenesis versus angiogenesis: similarities and differences.
        J Cell Mol Med. 2006; 10: 45-55
        • Davis J.W.
        Skin transplantation with a review of 550 cases at the Johns Hopkins Hospital.
        Johns Hopkins Med J. 1910; 15: 307-396
        • Sabella N.
        Use of fetal membranes in skin grafting.
        Med Records NY. 1913; 83: 478-480
        • Faulk W.P.
        • Matthews R.
        • Stevens P.J.
        • Bennett J.P.
        • Burgos H.
        • Hsi B.L.
        Human amnion as an adjunct in wound healing.
        Lancet. 1980; 1: 1156-1158
        • Kim J.C.
        • Tseng S.C.
        Transplantation of preserved human amniotic membrane for surface reconstruction in severely damaged rabbit corneas.
        Cornea. 1995; 14: 473-484
        • Koh J.W.
        • Shin J.W.
        • Oh J.Y.
        • Kim M.K.
        • Ko J.H.
        • Hwang J.M.
        • Wee W.R.
        • Lee J.H.
        The expression of TIMPs in cryo-preserved and freeze dried amniotic membrane.
        Curr Eye Res. 2007; 32: 611-616
        • Gruss J.S.
        Human amniotic membrane: a versatile wound dressing.
        Can Med Assoc J. 1978; 118: 1237-1246
        • Adinolfi M.
        HLA typing of amniotic fluid cells.
        Prenat Diagn. 1982; 2: 147
        • Adinolfi M.
        • Akle C.A.
        • McColl I.
        • Fensom A.H.
        • Tansley L.
        • Connolly P.
        • Hsi B.L.
        • Faulk W.P.
        • Travers P.
        • Bodmer W.F.
        Expression of HLA antigens, beta 2-microglobulin and enzymes by human amniotic epithelial cells.
        Nature. 1982; 295: 325-327
        • Akle C.A.
        • Adinolfi M.
        • Welsh K.I.
        • Leibowitz S.
        • McColl I.
        Immunogenicity of human amniotic epithelial cells after transplantation into volunteers.
        Lancet. 1981; 2: 1003-1005
        • Delo D.M.
        • De Coppi P.
        • Bartsch Jr., G.
        • Atala A.
        Amniotic fluid and placental stem cells.
        Methods Enzymol. 2006; 419: 426-438
        • Trelford J.D.
        • Trelford-Sauder M.
        The amnion in surgery, past and present.
        Am J Obstet Gynecol. 1979; 134: 833-845
        • Ucakhan O.O.
        • Koklu G.
        • Firat E.
        Nonpreserved human amniotic membrane transplantation in acute and chronic chemical eye injuries.
        Cornea. 2002; 21: 169-172
        • Akle C.A.
        • Adinolfi M.
        • Welsh K.I.
        Immunogenicity of human amniotic epithelial cells after transplantation into volunteers.
        Lancet. 1981; 2: 1003-1005
        • Solomon A.
        • Wajngarten M.
        • Alviano F.
        • Anteby I.
        • Elchalal U.
        • Pe'er J.
        • Levi-Schaffer F.
        Suppression of inflammatory and fibrotic responses in an in-vitro model of allergic inflammation by the amniotic membrane stromal matrix.
        Clin Exp Allergy. 2005; 35: 941-948
        • Perin L.
        • Sedrakyan S.
        • Da Sacco S.
        • De Filippo R.
        Characterization of human amniotic fluid stem cells and their pluripotential capability.
        Methods Cell Biol. 2008; 86: 85-99
        • Zhang Y.
        • Li C.
        • Jiang X.
        • Zhang S.
        • Wu Y.
        • Liu B.
        • Tang P.
        • Mao N.
        Human placenta-derived mesenchymal progenitor cells support culture expansion of long-term culture-initiating cells from cord blood CD34+ cells.
        Exp Hematol. 2004; 32: 657-664
        • Pasquinelli G.
        • Tazzari P.
        • Ricci F.
        • Orrico C.
        • Vaselli C.
        • Buzzi M.
        • Foroni L.
        • Alviano F.
        • Lucarelli E.
        • Bagnara G.P.
        • Stella A.
        • Conte R.
        Ultrastructural characteristics of human mesenchymal stromal (stem) cells derived from bone marrow and term placenta.
        Ultrastruct Pathol. 2007; 31: 23-31
        • Bailo M.
        • Soncini M.
        • Vertua E.
        • Signoroni P.B.
        • Sanzone S.
        • Lombardi G.
        • Arienti D.
        • Calamani F.
        • Zatti D.
        • Paul P.
        • Albertini A.
        • Zorzi F.
        • Cavagnini A.
        • Candotti F.
        • Wengler G.S
        • Parolini O.
        Engraftment potential of human amnion and chorion cells derived from term placenta.
        Transplantation. 2004; 78: 1439-1448
        • Loh Y.H.
        • Wu Q.
        • Chew J.L.
        • Vega V.B.
        • Zhang W.
        • Chen X.
        • Bourque G.
        • George J.
        • Leong B.
        • Liu J.
        • Wong K.Y.
        • Sung K.W.
        • Lee C.W.
        • Zhao X.D.
        • Chiu K.P.
        • Lipovich L.
        • Kuznetsov V.A.
        • Robson P.
        • Stanton L.W.
        • Wei C.L.
        • Ruan Y.
        • Lim B.
        • Ng H.H.
        The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells.
        Nat Genet. 2006; 38: 431-440
        • Brichard S.M.
        • Delporte M.L.
        • Lambert M.
        Adipocytokines in anorexia nervosa: a review focusing on leptin and adiponectin.
        Horm Metab Res. 2003; 35: 337-342
        • Jones K.R.
        • Fennie K.
        • Lenihan A.
        Evidence-based management of chronic wounds.
        Adv Skin Wound care. 2007; 20: 591-600
        • Carter M.J.
        • Fife C.E.
        • Walker D.
        • Thomson B.
        Estimating the applicability of wound care randomized controlled trials to general wound-care populations by estimating the percentage of individuals excluded from a typical wound-care population in such trials.
        Adv Skin Wound Care. 2009; 22: 316-324
        • Hunt T.K.
        • La Van F.B.
        Enhancement of wound healing by growth factors.
        N Engl J Med. 1989; 321: 111-112
        • Braund R.
        • Hook S.
        • Medlicott N.J.
        The role of topical growth factors in chronic wounds.
        Curr Drug Deliv. 2007; 4: 195-204
        • Werner S.
        • Grose R.
        Regulation of wound healing by growth factors and cytokines.
        Physiol Rev. 2003; 83: 835-870
        • Barrientos S.
        • Stojadinovic O.
        • Golinko M.S.
        • Brem H.
        • Tomic-Canic M.
        Growth factors and cytokines in wound healing.
        Wound Repair Regen. 2008; 16: 585-601
        • Singer A.J.
        • Clark R.A.
        Cutaneous wound healing.
        N Engl J Med. 1999; 341: 738-746
        • Everts P.A.
        • Brown Mahoney C.
        • Hoffmann J.J.
        • Schonberger J.P.
        • Box H.A.
        • van Zundert A.
        • Knape J.T.
        Platelet-rich plasma preparation using three devices: implications for platelet activation and platelet growth factor release.
        Growth Factors. 2006; 24: 165-171
        • Steed D.L.
        • Goslen J.B.
        • Holloway G.A.
        • Malone J.M.
        • Bunt T.J.
        • Webster M.W.
        Randomized prospective double-blind trial in healing chronic diabetic foot ulcers: CT-102 activated platelet supernatant, topical versus placebo.
        Diabetes Care. 1992; 15: 1598-1604
        • Knighton D.R.
        • Fiegel V.D.
        Regulation of cutaneous wound healing by growth factors and the microenvironment.
        Investig Radiol. 1991; 26: 604-611
        • Knighton D.R.
        • Ciresi K.
        • Fiegel V.D.
        • Schumerth S.
        • Butler E.
        • Cerra F.
        Stimulation of repair in chronic, nonhealing, cutaneous ulcers using platelet-derived wound healing formula.
        Surg Gynecol Obstet. 1990; 170: 56-60
        • Keyser J.E.
        Diabetic wound healing and limb salvage in an outpatient wound care program.
        South Med J. 1993; 86: 311-317
        • Glover J.L.
        • Weingarten M.S.
        • Buchbinder D.S.
        • Poucher R.L.
        • Deitrick III, G.A.
        • Fylling C.P.
        A 4-year outcome-based retrospective study of wound healing and limb salvage in patients with chronic wounds.
        Adv Wound Care. 1997; 10: 33-38
        • Atri S.C.
        • Misra J.
        • Bisht D.
        • Misra K.
        Use of homologous platelet factors in achieving total healing of recalcitrant skin ulcers.
        Surgery. 1990; 108: 508-512
        • Anitua E.
        • Andia I.
        • Ardanza B.
        • Nurden P.
        • Nurden A.T.
        Autologous platelets as a source of proteins for healing and tissue regeneration.
        Thromb Haemost. 2004; 91: 4-15
        • Prusa A.R.
        • Marton E.
        • Rosner M.
        • Bernaschek G.
        • Hengstschlager M.
        Oct4-expressing cells in human amniotic fluid: a new source for stem cell research?.
        Hum Reprod. 2003; 18: 1489-1493
        • Shearer A.
        • Scuffham P.
        • Gordois A.
        • Oglesby A.
        Predicted costs and outcomes from reduced vibration detection in people with diabetes in the U.S..
        Diabetes Care. 2003; 26: 2305-2310
        • Stute N.
        • Holtz K.
        • Bubenheim M.
        • Lange C.
        • Blake F.
        • Zander A.R.
        Autologous serum for isolation and expansion of human mesenchymal stem cells for clinical use.
        Exp Hematol. 2004; 32: 1212-1225
        • Deans R.J.
        • Moseley A.B.
        Mesenchymal stem cells: biology and potential clinical uses.
        Exp Hematol. 2000; 28: 875-884
        • Liu L.
        • Sun Z.
        • Chen B.
        • Han Q.
        • Liao L.
        • Jia M.
        • Cao Y.
        • Ma J.
        • Sun Q.
        • Guo M.
        • Liu Z.
        • Ai H.
        • Zhao R.C.
        Ex vivo expansion and in vivo infusion of bone marrow-derived Flk-1+CD31−CD34− mesenchymal stem cells: feasibility and safety from monkey to human.
        Stem Cells Dev. 2006; 15: 349-357
        • Hollander A.P.
        • Dickinson S.C.
        • Sims T.J.
        • Brun P.
        • Cortivo R.
        • Kon E.
        • Marcacci M.
        • Zanasi S.
        • Borrione A.
        • De Luca C.
        • Pavesio A.
        • Soranzo C.
        • Abatangelo G.
        Maturation of tissue engineered cartilage implanted in injured and osteoarthritic human knees.
        Tissue Eng. 2006; 12: 1787-1798