Restricted accessResearch articleFirst published online 2014-02
Human Endometrial Mesenchymal Stem Cells Modulate the Tissue Response and Mechanical Behavior of Polyamide Mesh Implants for Pelvic Organ Prolapse Repair
Pelvic organ prolapse (POP) is defined as the descent of one or more of the pelvic structures into the vagina and includes uterine, vaginal vault, and anterior or posterior vaginal wall prolapse. The treatment of POP may include implantation of a synthetic mesh. However, the long-term benefit of mesh surgery is controversial due to complications such as mesh exposure or pain. The aim of this study was to use a tissue engineering (TE) approach to assess the in vivo biological and biomechanical behavior of a new gelatin/polyamide mesh, seeded with a novel source of mesenchymal stem cells in a subcutaneous rat model of wound repair.
Methods:
W5C5-enriched human endometrial mesenchymal stem cells (eMSC) were seeded onto meshes (gelatin-coated polyamide knit) at 100,000 cells/cm2. Meshes, with or without cells were subcutaneously implanted dorsally in immunocompromised rats for 7, 30, 60, and 90 days. Flow cytometry was used to detect DiO labeled cells after explantation. Immunohistochemical assessment of foreign body reaction and tissue integration were conducted. Total collagen and the levels of collagens type III and type I were determined. Uniaxial tensiometry was performed on explanted meshes, originally seeded with and without cells, at days 7 and 90.
Results:
Implanted meshes were well tolerated, with labeled cells detected on the mesh up to 14 days postimplantation. Meshes with cells promoted significantly more neovascularization at 7 days (p<0.05) and attracted fewer macrophages at 90 days (p<0.05). Similarly, leukocyte infiltration was significantly lower in the cell-seeded meshes at 90 days (p<0.05). Meshes with cells were generally less stiff than those without cells, after 7 and 90 days implantation.
Conclusion:
The TE approach used in this study significantly reduced the number of inflammatory cells around the implanted mesh and promoted neovascularization. Seeding with eMSC exerts an anti-inflammatory effect and promotes wound repair with new tissue growth and minimal fibrosis, and produces mesh with greater extensibility. Cell seeding onto polyamide/gelatin mesh improves mesh biocompatibility and may be an alternative option for future treatment of POP.
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References
1.
HaylenB.T., de RidderD., FreemanR.M., SwiftS.E., BerghmansB., LeeJ., et al.An International Urogynecological Association (IUGA)/International Continence Society (ICS) Joint Report on the Terminology for Female Pelvic Floor Dysfunction. Neurourol Urodyn, 29, 4, 2010.
2.
HunskaarS., BurgioK., ClarkA., LapitanM.C., NelsonR., SillenU., et al.Epidemiology of urinary (UI) and faecal (FI) incontinence and pelvic organ prolapse (POP). Available at: www.icsoffice.org/Publications/ICI_3/v1.pdf/chap5.pdf2005. Last accessed August18, 2013.
3.
NygaardI., BarberM.D., BurgioK.L., KentonK., MeikleS., SchafferJ., et al.Prevalence of symptomatic pelvic floor disorders in US women. Jama, 300, 1311, 2008.
4.
StanfordE.J., CassidentiA., and MoenM.D.Traditional native tissue versus mesh-augmented pelvic organ prolapse repairs: providing an accurate interpretation of current literature. Int Urogynecol J, 23, 19, 2012.
5.
MaherC., FeinerB., BaesslerK., AdamsE.J., HagenS., and GlazenerC.M.Surgical management of pelvic organ prolapse in women. Cochrane Database Syst Rev, 4, CD004014, 2010.
6.
KonstantinovicM.L., PilleE., MalinowskaM., VerbekenE., De RidderD., and DeprestJ.Tensile strength and host response towards different polypropylene implant materials used for augmentation of fascial repair in a rat model. Int Urogynecol J Pelvic Floor Dysfunct, 18, 619, 2007.
7.
DelanceyJ.O.L.Anatomic aspects of vagianl eversion after hysterectomy. Am J Obstet Gynecol, 166, 1717, 1992.
FDA Safety Communication: UPDATE on Serious Complications Associated with Transvaginal Placement of Surgical Mesh for Pelvic Organ Prolapse. 2011. Available at: www.fda.gov/MedicalDevices/Safety/AlertsandNotices/UCM262435.htm. Last accessed August18, 2013.
10.
DeprestJ., ZhengF., KonstantinovicM., SpelziniF., ClaerhoutF., SteensmaA., et al.The biology behind fascial defects and the use of implants in pelvic organ prolapse repair. Int Urogynecol J Pelvic Floor Dysfunct, 17(Suppl 1), S16, 2006.
11.
de TayracR., AlvesA., and TherinM.Collagen-coated vs noncoated low-weight polypropylene meshes in a sheep model for vaginal surgery. A pilot study. Int Urogynecol J Pelvic Floor Dysfunct, 18, 513, 2007.
12.
LimY.N., MullerR., CorstiaansA., HitchinsS., BarryC., and RaneA.A long-term review of posterior colporrhaphy with Vypro 2 mesh. Int Urogynecol J Pelvic Floor Dysfunct, 18, 1053, 2007.
13.
ShiY., HuG., SuJ., LiW., ChenQ., ShouP., et al.Mesenchymal stem cells: a new strategy for immunosuppression and tissue repair. Cell Res, 20, 510, 2010.
14.
HoM.H., HeydarkhanS., VernetD., KovaneczI., FerriniM.G., BhatiaN.N., et al.Stimulating vaginal repair in rats through skeletal muscle-derived stem cells seeded on small intestinal submucosal scaffolds. Obstet Gynecol, 114, 300, 2009.
15.
DeprestJ., De RidderD., RooversJ.P., WerbrouckE., CoremansG., and ClaerhoutF.Medium term outcome of laparoscopic sacrocolpopexy with xenografts compared to synthetic grafts. J Urol, 182, 2362, 2009.
16.
DolceC.J., StefanidisD., KellerJ.E., WaltersK.C., NewcombW.L., HeathJ.J., et al.Pushing the envelope in biomaterial research: initial results of prosthetic coating with stem cells in a rat model. Surg Endosc, 24, 2687, 2010.
17.
GargettC.E., NguyenH.P.T., and YeL.Endometrial regeneration and endometrial stem/progenitor cells. Rev Endocr Metab Disord, 13, 235, 2012.
18.
GargettC.E., SchwabK.E., ZillwoodR.M., NguyenH.P., and WuD.Isolation and culture of epithelial progenitors and mesenchymal stem cells from human endometrium. Biol Reprod, 80, 1136, 2009.
MasudaH., AnwarS.S., BuehringH-J., RaoJ.R., and GargettC.E.A novel marker of human endometrial mesenchymal stem-like cells. Cell Transplant, 21, 2201, 2012.
21.
RajaramanG., WhiteJ., TanK.S., UlrichD., RosamiliaA., WerkmeisterJ.A., et al.Optimisation and scale up culture of human endometrial multipotent mesenchymal stromal cells: potential for clinical application. Tissue Eng Part C Methods, 19, 80, 2013.
22.
EdwardsS.L., WerkmeisterJ.A., RosamiliaA., RamshawJ.A.M., WhiteJ.F., and GargettC.E.Characterisation of clinical and newly fabricated meshes for pelvic organ prolapse repair. J Mech Behav Biomed Mater, 23, 53, 2013.
23.
UlrichD., EdwardsS.L., WhiteJ.F., SupitT., RamshawJ.A.M., LoC., et al.A preclinical evaluation of alternative synthetic biomaterials for fascial defect repair using a rat abdominal hernia model. PLoS One, 7, 2012.
24.
SchwabK.E., and GargettC.E.Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium. Hum Reprod, 22, 2903, 2007.
25.
BuhringH.J., BattulaV.L., TremlS., ScheweB., KanzL., and VogelW.Novel markers for the prospective isolation of human MSC. Ann N Y Acad Sci, 1106, 262, 2007.
26.
DominiciM., Le BlancK., MuellerI., Slaper-CortenbachI., MariniF., KrauseD., et al.Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8, 315, 2006.
27.
JunqueiraL.C.U., BignolasG., and BrentaniR.R.Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue-sections. Histochem J, 11, 447, 1979.
28.
SykesB., PuddleB., FrancisM., and SmithR.Estimation of 2 collagens from human dermis by interrupted gel-electrophoresis. Biochemical and Biophys Res Commun, 72, 1472, 1976.
29.
ChanD., and ColeWG.Quantitation of type I and type-III collagens using electrophoresis of alpha chains and cyanogen-bromide peptides. Anal Biochem, 139, 322, 1984.
30.
RubodC., BoukerrouM., BrieuM., DuboisP., and CossonM.Biomechanical properties of vaginal tissue. Part 1: new experimental protocol. J Urol, 178, 320, 2007.
31.
De PhilippoR.E., BishopC.E., FreitasL., YooJ.J., and AtalaA.Tissue engineering a complete vaginal replacement from a small biopsy of autologous tissue. Transplantation, 86, 208, 2008.
32.
HungM.J., WenM.C., HungC.N., HoE.S.C., ChenG.D., and YangV.C.Tissue-engineered fascia from vaginal fibroblasts for patients needing reconstructive pelvic surgery. Int Urogynecol J, 21, 1085, 2010.
33.
de FilippoR.E., YooJ.J., and AtalaA.Engineering of vaginal tissue in vivo. Tissue Eng, 9, 301, 2003.
34.
MartinI., BaldomeroH., Bocelli-TyndallC., PasswegJ., SarisD., and TyndallA.The Survey on Cellular and Engineered Tissue Therapies in Europe in 2010. Tissue Eng Part A, 18, 2268, 2012.
35.
UlrichD., MuralitharanR., and GargettC.Toward the use of endometrial and menstrual blood mesenchymal stem cells for cell-based therapies. Expert Opin Biol Ther, 13, 1387, 2013.
36.
CaplanA.I., and DennisJ.E.Mesenchymal stem cells as trophic mediators. J Cell Biochem, 98, 1076, 2006.
37.
Di NicolaM., Carlo-StellaC., MagniM., MilanesiM., LongoniP.D., MatteucciP., et al.Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood, 99, 3838, 2002.
38.
MantovaniA., SicaA., and LocatiM.Macrophage polarization comes of age. Immunity, 23, 344, 2005.
39.
BadylakS.F., ValentinJ.E., RavindraA.K., McCabeG.P., and Stewart-AkersA.M.Macrophage phenotype as a determinant of biologic scaffold remodeling. Tissue Eng Part A, 14, 1835, 2008.
40.
BrownB.N., LondonoR., TotteyS., ZhangL., KuklaK.A., WolfM.T., et al.Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials. Acta Biomater, 8, 978, 2012.
41.
HsiaoS.T.-F., AsgariA., LokmicZ., SinclairR., DustingG.J., LimS.Y., et al.Comparative analysis of paracrine factor expression in human adult mesenchymal stem cells derived from bone marrow, adipose, and dermal tissue. Stem Cells Dev, 21, 2189, 2012.
42.
MidwoodK.S., WilliamsL.V., and SchwarzbauerJ.E.Tissue repair and the dynamics of the extracellular matrix. Int J Biochem Cell Biol, 36, 1031, 2004.
43.
ProckopD.J., and KivirikkoK.I.Collagens-molecular-biology, diseases, and potentials for therapy. Annu Rev Biochem, 64, 403, 1995.
44.
GelseK., PoschlE., and AignerT.Collagens—structure, function, and biosynthesis. Adv Drug Deliv Rev, 55, 1531, 2003.
45.
DoillonC.J., DunnM.G., BenderE., and SilverF.H.Collagen fiber formation in repair tissue-development of strength and toughness. Coll Relat Res, 5, 481, 1985.
46.
JungeK., KlingeU., KlosterhalfenB., MertensP.R., RoschR., SchachtruppA., et al.Influence of mesh materials on collagen deposition in a rat model. J Invest Surg, 15, 319, 2002.
47.
FeolaA., AbramowitchS., JonesK., SteinS., and MoalliP.Parity negatively impacts vaginal mechanical properties and collagen structure in rhesus macaques. Am J Obstet Gynecol, 203, 2010.
48.
DayanD., HissY., HirshbergA., BubisJ.J., and WolmanM.Are the polarization colors of Picrosirius Red-stained collagen determined only by the diameter of the fibres. Histochemistry, 93, 27, 1989.
49.
Jean-CharlesC., RubodC., BrieuM., BoukerrouM., FaselJ., and CossonM.Biomechanical properties of prolapsed or non-prolapsed vaginal tissue: impact on genital prolapse surgery. Int Urogynecol J, 21, 1535, 2010.
50.
SalamonsenL.A.Tissue injury and repair in the female human reproductive tract. Reproduction, 125, 301, 2003.
51.
FeolaA., AbramowitchS., JallahZ., SteinS., BaroneW., PalcseyS., et al.Deterioration in biomechanical properties of the vagina following implantation of a high-stiffness prolapse mesh. BJOG, 120, 224, 2013.
52.
von BahrL., BatsisI., MollG., HaggM., SzakosA., SundbergB., et al.Analysis of tissues following mesenchymal stromal cell therapy in humans indicates limited long-term engraftment and no ectopic tissue formation. Stem Cells, 30, 1575, 2012.
53.
ZimmermannC.E., GierloffM., HedderichJ., AcilY., WiltfangJ., and TerheydenH.Survival of transplanted rat bone marrow-derived osteogenic stem cells in vivo. Tissue Eng Part A, 17, 1147, 2011.
54.
PolzerH., VolkmerE., SallerM.M., PrallW.C., HaastersF., DrosseI., et al.Long-term detection of fluorescently labeled human mesenchymal stem cell in vitro and in vivo by semi-automated microscopy. Tissue Eng Part C Methods, 18, 156, 2012.
55.
DeprestJ., and FeolaA.The need for preclinical research on pelvic floor reconstruction. BJOG, 120, 141, 2013.
56.
KonstantinovicM.L., LagaeP., ZhengF., VerbekenE.K., De RidderD., and DeprestJ.A.Comparison of host response to polypropylene and non-cross-linked porcine small intestine serosal-derived collagen implants in a rat model. BJOG, 112, 1554, 2005.
57.
AbramowitchS.D., FeolaA., JallahZ., and MoalliP.A.Tissue mechanics, animal models, and pelvic organ prolapse: A review. Eur J Obstet Gynecol Reprod Biol, 144, S146, 2009.
58.
Frey-VasconcellsJ., WhittleseyK.J., BaumE., and FeigalE.G.Translation of stem cell research: points to consider in designing preclinical animal studies. Stem Cells Transl Med, 1, 353, 2012.
59.
AtalaA.Tissue engineering of reproductive tissues and organs. Fertil Steril, 98, 21, 2012.
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