International Urogynecology Journal

, Volume 26, Issue 5, pp 675–683 | Cite as

Stem cell augmented mesh materials: an in vitro and in vivo study

  • Federico Spelzini
  • Stefano ManodoroEmail author
  • Matteo Frigerio
  • Gabriella Nicolini
  • Daniele Maggioni
  • Elisabetta Donzelli
  • Lina Altomare
  • Silvia Farè
  • Fanny Veneziano
  • Federica Avezza
  • Giovanni Tredici
  • Rodolfo Milani
Original Article


Introduction and hypothesis

To test in vitro and in vivo the capability of mesh materials to act as scaffolds for rat-derived mesenchymal stem cells (rMSCs) and to compare inflammatory response and collagen characteristics of implant materials, either seeded or not with rMSCs.


rMSCs isolated from rat bone marrow were seeded and cultured in vitro on four different implant materials. Implants showing the best rMSC proliferation rate were selected for the in vivo experiment. Forty-eight adult female Sprague–Dawley rats were randomly divided into two treatment groups. The implant of interest—either seeded or not with rMSCs—was laid and fixed over the muscular abdominal wall. Main outcome measures were: in vitro, proliferation of rMSCs on selected materials; in vivo, the occurrence of topical complications, the evaluation of systemic and local inflammatory response and examination of the biomechanical properties of explants.


Surgisis and Pelvitex displayed the best cell growth in vitro. At 90 days in the rat model, rMSCs were related to a lower count of neutrophil cells for Pelvitex and a greater organisation and collagen amount for Surgisis. At 7 days Surgisis samples seeded with rMSCs displayed higher breaking force and stiffness.


The presence of rMSCs reduced the systemic inflammatory response on synthetic implants and improved collagen characteristics at the interface between biological grafts and native tissues. rMSCs enhanced the stripping force on biological explants.


Mesh Stem cells Graft-related complications 



Maximum force before the separation of the mesh from the abdominal wall


Foreign body giant cells




Mesenchymal stem cells


Polymorphonuclear cells


Pelvitex without rMSCs


Pelvic organ prolapse




Pelvitex with rMSCs


Rat-derived mesenchymal stem cells




Secant modulus at 30 % elongation


Secant modulus at 50 % elongation


Small intestine submucosa


Small intestine submucosa without rMSCs


Small intestine submucosa with rMSCs


Maximum elongation before the separation of the mesh from the abdominal wall


Conflicts of interest


Supplementary material

192_2014_2570_MOESM1_ESM.pdf (61 kb)
ESM 1 (PDF 61 kb)
192_2014_2570_MOESM2_ESM.doc (20 kb)
ESM 2 (DOC 19 kb)


  1. 1.
    MacLennan AH, Taylor AW, Wilson DH, Wilson D (2000) The prevalence of pelvic floor disorders and their relation to gender, age, parity, and mode of delivery. Br J Obstet Gynaecol 106:1460–1470CrossRefGoogle Scholar
  2. 2.
    Birch C, Fynes MM (2002) The role of synthetic and biological prostheses in reconstructive pelvic floor surgery. Curr Opin Gynecol Obstet 14:527–535CrossRefGoogle Scholar
  3. 3.
    Olsen AL, Smith VJ, Bergstrom JO, Colling JC, Clark AL (1997) Epidemiology of surgically managed pelvic organ prolapse and urinary incontinence. Obstet Gynecol 89:501–506CrossRefPubMedGoogle Scholar
  4. 4.
    Baessler K, Maher CF (2006) Mesh augmentation during pelvic-floor reconstructive surgery: risks and benefits. Curr Opin Obstet Gynecol 18:560–566CrossRefPubMedGoogle Scholar
  5. 5.
    Cobb WS, Kercher KW, Heniford BT (2005) The argument for lightweight polypropylene mesh in hernia repair. Surg Innov 12(1):63–69, reviewGoogle Scholar
  6. 6.
    Deprest J, Claerhout F, Zheng F, Kostantinovic M, Spelzini F, Guelinckx I et al (2005) Synthetic and biodegradable prostheses in pelvic floor surgery. Int Congr Ser 1279:387–397CrossRefGoogle Scholar
  7. 7.
    Nazemi TM, Kobashi KC (2007) Complications of grafts used in female pelvic floor reconstruction: mesh erosion and extrusion. Indian J Urol 23:153–160CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Fibbe WE. Mesenchymal stem cells. A potential source for skeletal repair. Ann Rheum Dis 2002;61 [Suppl II]:ii29–ii31.CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Caplan AI (2007) Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 213(2):341–347CrossRefPubMedGoogle Scholar
  10. 10.
    Meinel L, Karageorgiou V, Fajardo R, Snyder B, Shinde-Patil V, Zichner L et al (2004) Bone tissue engineering using human mesenchymal stem cells: effects of scaffold material and medium flow. Ann Biomed Eng 32:112–122CrossRefPubMedGoogle Scholar
  11. 11.
    Rasmusson I (2006) Immune modulation by mesenchymal stem cells. Exp Cell Res 312:2169–2179CrossRefPubMedGoogle Scholar
  12. 12.
    Ochoa I, Peña E, Andreu EJ, Pérez-Ilzarbe M, Robles JE, Alcaine C et al (2011) Mechanical properties of cross-linked collagen meshes after human adipose derived stromal cells seeding. J Biomed Mater Res A 96(2):341–348CrossRefPubMedGoogle Scholar
  13. 13.
    Voytik-Harbin SL, Brightman AO, Kraine MR, Waisner B, Badylak SF (1997) Identification of extractable growth factors from small intestinal submucosa. J Cell Biochem 67:478–491CrossRefPubMedGoogle Scholar
  14. 14.
    Gandhi S, Kubba LM, Abramov Y, Botros SM, Goldberg RP, Victor TA et al (2005) Histopathologic changes of porcine dermis xenografts for transvaginal suburethral slings. Am J Obstet Gynecol 192:1643–1648CrossRefPubMedGoogle Scholar
  15. 15.
    De Tayrac R, Alves A, Therin M (2007) Collagen-coated vs noncoated low-weight polypropylene meshes in a sheep model for vaginal surgery. A pilot study. Int Urogynecol J 18:513–520CrossRefGoogle Scholar
  16. 16.
    Mutter D, Jamali FR, Moody DL, Rodeheaver GT, Therin M, Marescu J (2000) The concept of protected mesh to minimize adhesion formation in intraperitoneal abdominal wall reinforcement. preclinical evaluation of a new composite mesh. Hernia 4 [Suppl]:S3–S9CrossRefGoogle Scholar
  17. 17.
    Donzelli E, Salvadè A, Mimo P, Viganò M, Morrone M, Papagna R et al (2007) Mesenchymal stem cells cultured on a collagen scaffold: in vitro osteogenic differentiation. Arch Oral Biol 52(1):64–73CrossRefPubMedGoogle Scholar
  18. 18.
    Badylak S, Kokini K, Tullius B, Simmons-Byrd A, Morff R (2002) Morphologic study of small intestinal submucosa as a body wall repair device. J Surg Res 103(2):190–202CrossRefPubMedGoogle Scholar
  19. 19.
    Konstantinovic ML, Lagae P, Zheng F, Verbeken KE, De Ridder D, Deprest JA (2005) Comparison of host response to polypropylene and non-cross-linked porcine small intestine serosal-derived collagen implants in a rat model. BJOG 112:1554–1560CrossRefPubMedGoogle Scholar
  20. 20.
    Morishita T, Honoki K, Ohgushi H, Kotobuki N, Matsushima A, Takakura Y (2006) Tissue engineering approach to the treatment of bone tumors: three cases of cultured bone grafts derived from patients’ mesenchymal stem cells. Artif Organs 30(2):115–118CrossRefPubMedGoogle Scholar
  21. 21.
    Janssens S, Dubois C, Bogaert J, Theunissen K, Deroose C, Desmet W et al (2006) Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet 367:113–121CrossRefPubMedGoogle Scholar
  22. 22.
    Yamamoto T, Gotoh M, Kato M, Majima T, Toriyama K, Kamei Y et al (2012) Periurethral injection of autologous adipose-derived regenerative cells for the treatment of male stress urinary incontinence: report of three initial cases. Int J Urol 19(7):652–659CrossRefPubMedGoogle Scholar
  23. 23.
    Ahn HH, Kim KS, Lee JH, Lee MS, Song IB, Cho MH et al (2007) Porcine small intestinal submucosa sheets as a scaffold for human bone marrow stem cells. Int J Biol Macromol 41(5):590–596CrossRefPubMedGoogle Scholar
  24. 24.
    Klosterhalfen B, Klinge U, Schumpelick V (1998) Functional and morphological evaluation of different polypropylene-mesh modifications for abdominal wall repair. Biomaterials 19:2235–2246CrossRefPubMedGoogle Scholar
  25. 25.
    Dolce CJ, Stefanidis D, Keller JE, Walters KC, Newcomb WL, Heath JJ et al (2010) Pushing the envelope in biomaterial research: initial results of prosthetic coating with stem cells in a rat model. Surg Endoscop 24(11):2687–2693CrossRefGoogle Scholar
  26. 26.
    Altman AM, Abdul Khalek FJ, Alt EU, Butler CE (2010) Adipose tissue– derived stem cells enhance Bioprosthetic mesh repair of ventral hernias. Plast Reconstr Surg 126(3):845–854CrossRefPubMedGoogle Scholar
  27. 27.
    Mouritsen L, Kronschnabl M, Lose G (2010) Long-term results of vaginal repairs with and without xenograft reinforcement. Int Urogynecol J Pelvic Floor Dysfunct 21:467–473CrossRefGoogle Scholar
  28. 28.
    Ozog Y, Konstantinovic ML, Verschueren S, Spelzini F, De RD, Deprest J (2009) Experimental comparison of abdominal wall repair using different methods of enhancement by small intestinal submucosa graft. Int Urogynecol J Pelvic Floor Dysfunct 20:435–441CrossRefPubMedGoogle Scholar
  29. 29.
    Boennelycke M, Gras S, Lose G (2013) Tissue engineering as a potential alternative or adjunct to surgical reconstruction in treating pelvic organ prolapse. Int Urogynecol J 24:741–747CrossRefPubMedGoogle Scholar
  30. 30.
    Urogynecologic surgical mesh: update on the safety and effectiveness of transvaginal placement for pelvic organ prolapse. July 2011
  31. 31.
    Hilger WS, Walter A, Zobit ME, Leslie KO, Magtibay P, Cornella J (2006) Histological and biomechanical evaluation of implanted graft materials in a rabbit vaginal and abdominal model. Am J Obstet Gynecol 195(6):1826–1831CrossRefPubMedGoogle Scholar
  32. 32.
    Manodoro S, Endo M, Uvin P, Albersen M, Vlacil J, Engels A et al (2013) Graft-related complications and biaxial tensiometry following experimental vaginal implantation of flat mesh of variable dimensions. BJOG 120:244–250CrossRefPubMedGoogle Scholar

Copyright information

© The International Urogynecological Association 2014

Authors and Affiliations

  • Federico Spelzini
    • 1
  • Stefano Manodoro
    • 1
    • 2
    Email author
  • Matteo Frigerio
    • 1
  • Gabriella Nicolini
    • 3
  • Daniele Maggioni
    • 3
  • Elisabetta Donzelli
    • 3
  • Lina Altomare
    • 4
  • Silvia Farè
    • 4
  • Fanny Veneziano
    • 1
  • Federica Avezza
    • 3
  • Giovanni Tredici
    • 3
  • Rodolfo Milani
    • 1
  1. 1.Department of Obstetrics and Gynaecology, San Gerardo HospitalUniversity of Milano-BicoccaMonzaItaly
  2. 2.Department of Obstetrics and GynaecologyHospital of DesioDesioItaly
  3. 3.Department of Surgery and Interdisciplinary MedicineUniversity of Milano-BicoccaMonzaItaly
  4. 4.Department of Chemistry, Materials and Chemical Engineering “G. Natta” Politecnico di MilanoMilanItaly

Personalised recommendations