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Tissue engineering as a potential alternative or adjunct to surgical reconstruction in treating pelvic organ prolapse

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Abstract

Introduction and hypothesis

Cell-based tissue engineering strategies could potentially provide attractive alternatives to surgical reconstruction of native tissue or the use of surgical implants in treating pelvic organ prolapse (POP).

Methods

Based on a search in PubMed, this review focuses on candidate cell types, scaffolds, and trophic factors used in studies examining cell-based tissue engineering strategies to treat POP, stress urinary incontinence (SUI), and the closely related field of hernias.

Results

In contrast to the field of SUI, the use of cell-based tissue engineering strategies to treat POP are very sparsely explored, and only preclinical studies exist.

Conclusion

The available evidence suggests that the use of autologous muscle-derived cells, fibroblasts, or mesenchymal stem cells seeded on biocompatible, degradable, and potentially growth-promoting scaffolds could be an alternative to surgical reconstruction of native tissue or the use of conventional implants in treating POP. However, the vagina is a complex organ with great demands of functionality, and the perfect match of scaffold, cell, and trophic factor has yet to be found and tested in preclinical studies. Important issues such as safety and economy must also be addressed before this approach is ready for clinical studies.

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Abbreviations

POP:

Pelvic organ prolapse

SUI:

Stress urinary incontinence

PP:

Polypropylene

MDSC:

Muscle-derived stem cells

SIS:

Small intestine submucosa

MPEG:

Methoxy-poly-ethylene-glycol

PLGA:

Polylactic-co-glycolic acid

PGA:

Poly-glycolic acid

MSC:

Mesenchymal stem cells

BMSC:

Bone marrow mesenchymal stem cells

ADSC:

Adipose-tissue-derived stem cells

References

  1. Maher CM, Feiner B, Baessler K, Glazener CM (2011) Surgical management of pelvic organ prolapse in women: the updated summary version Cochrane review. Int Urogynecol J 22:1445–1457

    Article  PubMed  Google Scholar 

  2. Blandon RE, Gebhart JB, Trabuco EC, Klingele CJ (2009) Complications from vaginally placed mesh in pelvic reconstructive surgery. Int Urogynecol J Pelvic Floor Dysfunct 20:523–531

    Article  PubMed  Google Scholar 

  3. Diwadkar GB, Barber MD, Feiner B, Maher C, Jelovsek JE (2009) Complication and reoperation rates after apical vaginal prolapse surgical repair: a systematic review. Obstet Gynecol 113:367–373

    PubMed  Google Scholar 

  4. Maher C, Baessler K, Glazener CM, Adams EJ, Hagen S (2008) Surgical management of pelvic organ prolapse in women: a short version Cochrane review. Neurourol Urodyn 27:3–12

    Article  PubMed  CAS  Google Scholar 

  5. Sung VW, Rogers RG, Schaffer JI, Balk EM, Uhlig K, Lau J, Abed H, Wheeler TL, Morrill MY, Clemons JL, Rahn DD, Lukban JC, Lowenstein L, Kenton K, Young SB (2008) Graft use in transvaginal pelvic organ prolapse repair: a systematic review. Obstet Gynecol 112:1131–1142

    Article  PubMed  Google Scholar 

  6. Abed H, Rahn DD, Lowenstein L, Balk EM, Clemons JL, Rogers RG (2011) Incidence and management of graft erosion, wound granulation, and dyspareunia following vaginal prolapse repair with graft materials: a systematic review. Int Urogynecol J 22:789–798

    Article  PubMed  Google Scholar 

  7. Patel H, Ostergard DR, Sternschuss G (2012) Polypropylene mesh and the host response. Int Urogynecol J 23:669–679

    Article  PubMed  Google Scholar 

  8. Ostergard DR (2011) Degradation, infection and heat effects on polypropylene mesh for pelvic implantation: what was known and when it was known. Int Urogynecol J 22:771–774

    Article  PubMed  Google Scholar 

  9. Allahdin S, Glazener C, Bain C (2008) A randomised controlled trial evaluating the use of polyglactin mesh, polydioxanone and polyglactin sutures for pelvic organ prolapse surgery. J Obstet Gynaecol 28:427–431

    Article  PubMed  CAS  Google Scholar 

  10. Claerhout F, De RD, Van BD, Coremans G, Veldman J, Lewi P, Deprest J (2010) Sacrocolpopexy using xenogenic acellular collagen in patients at increased risk for graft-related complications. Neurourol Urodyn 29:563–567

    PubMed  Google Scholar 

  11. Feldner PC Jr, Castro RA, Cipolotti LA, Delroy CA, Sartori MG, Girao MJ (2010) Anterior vaginal wall prolapse: a randomized controlled trial of SIS graft versus traditional colporrhaphy. Int Urogynecol J Pelvic Floor Dysfunct 21:1057–1063

    Article  Google Scholar 

  12. Mouritsen L, Kronschnabl M, Lose G (2010) Long-term results of vaginal repairs with and without xenograft reinforcement. Int Urogynecol J Pelvic Floor Dysfunct 21:467–473

    Google Scholar 

  13. 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 20:435–441

    Article  PubMed  Google Scholar 

  14. Paraiso MF, Barber MD, Muir TW, Walters MD (2006) Rectocele repair: a randomized trial of three surgical techniques including graft augmentation. Am J Obstet Gynecol 195:1762–1771

    Article  PubMed  Google Scholar 

  15. Aboushwareb T, McKenzie P, Wezel F, Southgate J, Badlani G (2011) Is tissue engineering and biomaterials the future for lower urinary tract dysfunction (LUTD)/pelvic organ prolapse (POP)? Neurourol Urodyn 30:775–782

    Article  PubMed  CAS  Google Scholar 

  16. Badylak SF, Nerem RM (2010) Progress in tissue engineering and regenerative medicine. Proc Natl Acad Sci U S A 107:3285–3286

    Article  PubMed  CAS  Google Scholar 

  17. Demirbag B, Huri PY, Kose GT, Buyuksungur A, Hasirci V (2011) Advanced cell therapies with and without scaffolds. Biotechnol J 6:1437–1453

    Article  PubMed  CAS  Google Scholar 

  18. Olson JL, Atala A, Yoo JJ (2011) Tissue engineering: current strategies and future directions. Chonnam Med J 47:1–13

    Article  PubMed  CAS  Google Scholar 

  19. Mason C, Dunnill P (2008) A brief definition of regenerative medicine. Regen Med 3:1–5

    Article  PubMed  Google Scholar 

  20. De Filippo RE, Bishop CE, Filho LF, Yoo JJ, Atala A (2008) Tissue engineering a complete vaginal replacement from a small biopsy of autologous tissue. Transplantation 86:208–214

    Article  PubMed  Google Scholar 

  21. Raya-Rivera A, Esquiliano DR, Yoo JJ, Lopez-Bayghen E, Soker S, Atala A (2011) Tissue-engineered autologous urethras for patients who need reconstruction: an observational study. Lancet 377:1175–1182

    Article  PubMed  Google Scholar 

  22. Gras S, Lose G (2011) The clinical relevance of cell-based therapy for the treatment of stress urinary incontinence. Acta Obstet Gynecol Scand 90:815–824

    Article  PubMed  Google Scholar 

  23. Wang HJ, Chuang YC, Chancellor MB (2011) Development of cellular therapy for the treatment of stress urinary incontinence. Int Urogynecol J 22:1075–1083

    Article  PubMed  CAS  Google Scholar 

  24. Rubod C, Boukerrou M, Brieu M, Jean-Charles C, Dubois P, Cosson M (2008) Biomechanical properties of vaginal tissue: preliminary results. Int Urogynecol J Pelvic Floor Dysfunct 19:811–816

    Article  PubMed  Google Scholar 

  25. Ho MH, Heydarkhan S, Vernet D, Kovanecz I, Ferrini MG, Bhatia NN, Gonzalez-Cadavid NF (2009) Stimulating vaginal repair in rats through skeletal muscle-derived stem cells seeded on small intestinal submucosal scaffolds. Obstet Gynecol 114:300–309

    Article  PubMed  Google Scholar 

  26. Boennelycke M, Christensen L, Nielsen LF, Gras S, Lose G (2011) Fresh muscle fiber fragments on a scaffold in rats-a new concept in urogynecology? Am J Obstet Gynecol 205:235.e10–235.e14

    Google Scholar 

  27. Hung MJ, Wen MC, Hung CN, Ho ES, Chen GD, Yang VC (2010) Tissue-engineered fascia from vaginal fibroblasts for patients needing reconstructive pelvic surgery. Int Urogynecol J Pelvic Floor Dysfunct 21:1085–1093

    Article  Google Scholar 

  28. Deprest J, Zheng F, Konstantinovic M, Spelzini F, Claerhout F, Steensma A, Ozog Y, De RD (2006) 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–S25

    PubMed  Google Scholar 

  29. Slack M, Ostergard D, Cervigni M, Deprest J (2012) A standardized description of graft-containing meshes and recommended steps before the introduction of medical devices for prolapse surgery. Consensus of the 2nd IUGA Grafts Roundtable: optimizing safety and appropriateness of graft use in transvaginal pelvic reconstructive surgery. Int Urogynecol J 23(Suppl 1):S15–S26

    Article  PubMed  Google Scholar 

  30. Ayele T, Zuki AB, Noorjahan BM, Noordin MM (2010) Tissue engineering approach to repair abdominal wall defects using cell-seeded bovine tunica vaginalis in a rabbit model. J Mater Sci Mater Med 21:1721–1730

    Article  PubMed  CAS  Google Scholar 

  31. Drewa T, Galazka P, Prokurat A, Wolski Z, Sir J, Wysocka K, Czajkowski R (2005) Abdominal wall repair using a biodegradable scaffold seeded with cells. J Pediatr Surg 40:317–321

    Article  PubMed  Google Scholar 

  32. Falco EE, Roth JS, Fisher JP (2008) Skeletal muscle tissue engineering approaches to abdominal wall hernia repair. Birth Defects Res C Embryo Today 84:315–321

    Article  PubMed  CAS  Google Scholar 

  33. Fann SA, Terracio L, Yan W, Franchini JL, Yost MJ (2006) A model of tissue-engineered ventral hernia repair. J Invest Surg 19:193–205

    Article  PubMed  Google Scholar 

  34. Kunisaki SM, Fuchs JR, Kaviani A, Oh JT, LaVan DA, Vacanti JP, Wilson JM, Fauza DO (2006) Diaphragmatic repair through fetal tissue engineering: a comparison between mesenchymal amniocyte—and myoblast-based constructs. J Pediatr Surg 41:34–39

    Article  PubMed  Google Scholar 

  35. Lai JY, Chang PY, Lin JN (2003) Body wall repair using small intestinal submucosa seeded with cells. J Pediatr Surg 38:1752–1755

    Article  PubMed  Google Scholar 

  36. Propst JT, Fann SA, Franchini JL, Lessner SM, Rose JR, Hansen KJ, Terracio L, Yost MJ (2009) Focused in vivo genetic analysis of implanted engineered myofascial constructs. J Invest Surg 22:35–45

    Article  PubMed  Google Scholar 

  37. Thorrez L, Shansky J, Wang L, Fast L, VandenDriessche T, Chuah M, Mooney D, Vandenburgh H (2008) Growth, differentiation, transplantation and survival of human skeletal myofibers on biodegradable scaffolds. Biomaterials 29:75–84

    Article  PubMed  CAS  Google Scholar 

  38. Urita Y, Komuro H, Chen G, Shinya M, Saihara R, Kaneko M (2008) Evaluation of diaphragmatic hernia repair using PLGA mesh-collagen sponge hybrid scaffold: an experimental study in a rat model. Pediatr Surg Int 24:1041–1045

    Article  PubMed  Google Scholar 

  39. Valentin JE, Turner NJ, Gilbert TW, Badylak SF (2010) Functional skeletal muscle formation with a biologic scaffold. Biomaterials 31:7475–7484

    Article  PubMed  CAS  Google Scholar 

  40. Zhang L, Li Q, Qin J, Gu Y (2012) Musculature tissue engineering to repair abdominal wall hernia. Artif Organs 36:348–352

    Article  PubMed  Google Scholar 

  41. Cannon TW, Sweeney DD, Conway DA, Kamo I, Yoshimura N, Sacks M, Chancellor MB (2005) A tissue-engineered suburethral sling in an animal model of stress urinary incontinence. BJU Int 96:664–669

    Article  PubMed  Google Scholar 

  42. Zou XH, Zhi YL, Chen X, Jin HM, Wang LL, Jiang YZ, Yin Z, Ouyang HW (2010) Mesenchymal stem cell seeded knitted silk sling for the treatment of stress urinary incontinence. Biomaterials 31:4872–4879

    Article  PubMed  CAS  Google Scholar 

  43. Lecoeur C, Swieb S, Zini L, Riviere C, Combrisson H, Gherardi R, Abbou C, Yiou R (2007) Intraurethral transfer of satellite cells by myofiber implants results in the formation of innervated myotubes exerting tonic contractions. J Urol 178:332–337

    Article  PubMed  Google Scholar 

  44. Budatha M, Roshanravan S, Zheng Q, Weislander C, Chapman SL, Davis EC, Starcher B, Word RA, Yanagisawa H (2011) Extracellular matrix proteases contribute to progression of pelvic organ prolapse in mice and humans. J Clin Invest 121:2048–2059

    Article  PubMed  CAS  Google Scholar 

  45. Kapischke M, Prinz K, Tepel J, Tensfeldt J, Schulz T (2005) Precoating of alloplastic materials with living human fibroblasts—a feasibility study. Surg Endosc 19:791–797

    Article  PubMed  CAS  Google Scholar 

  46. Mangera A, Bullock AJ, Macneil S, Chapple C (2010) Developing an autologous tissue engineered prosthesis for use in stress urinary incontinence and pelvic organ prolapse (ICS-IUGA 2010 Abstracts). Int Urogynecol J Pelvic Floor Dysfunct 21:S325–S326

    Article  Google Scholar 

  47. Skala CE, Petry IB, Gebhard S, Hengstler JG, Albrich SB, Maltaris T, Naumann G, Koelbl H (2009) Isolation of fibroblasts for coating of meshes for reconstructive surgery: differences between mesh types. Regen Med 4:197–204

    Article  PubMed  CAS  Google Scholar 

  48. Zhao W, Zhang C, Jin C, Zhang Z, Kong D, Xu W, Xiu Y (2011) Periurethral injection of autologous adipose-derived stem cells with controlled-release nerve growth factor for the treatment of stress urinary incontinence in a rat model. Eur Urol 59:155–163

    Article  PubMed  CAS  Google Scholar 

  49. Dolce C, Stefanidis D, Keller J, Walters K, Newcomb W, Heath J, Norton H, Lincourt A, Kercher K, Heniford B (2010) Pushing the envelope in biomaterial research: initial results of prosthetic coating with stem cells in a rat model. Surg Endosc 24:2687–2693

    Google Scholar 

  50. Jakus SM, Shapiro A, Hall CD (2008) Biologic and synthetic graft use in pelvic surgery: a review. Obstet Gynecol Surv 63:253–266

    Article  PubMed  Google Scholar 

  51. Jones K, Feola A, Meyn L, Abramowitch S, Moalli P (2009) Tensile properties of commonly used prolapse meshes. Int Urogynecol J 20:847–853

    Article  Google Scholar 

  52. Albo M, Brubaker L, Daneshgari F (2006) Open and unresolved clinical questions in female pelvic medicine and reconstructive surgery. BJU Int 98(Suppl 1):110–116

    Article  PubMed  Google Scholar 

  53. Brubaker L, Richter HE, Norton PA, Albo M, Zyczynski HM, Chai TC, Zimmern P, Kraus S, Sirls L, Kusek JW, Stoddard A, Tennstedt S, Gormley EA (2012) 5-year continence rates, satisfaction and adverse events of burch urethropexy and fascial sling surgery for urinary incontinence. J Urol 187:1324–1330

    Article  PubMed  CAS  Google Scholar 

  54. McBride AW, Ellerkmann RM, Bent AE, Melick CF (2005) Comparison of long-term outcomes of autologous fascia lata slings with Suspend Tutoplast fascia lata allograft slings for stress incontinence. Am J Obstet Gynecol 192:1677–1681

    Article  PubMed  Google Scholar 

  55. Molsted-Pedersen L, Rudnicki M, Lose G (2006) Transvaginal repair of enterocele and vaginal vault prolapse using autologous fascia lata graft. Acta Obstet Gynecol Scand 85:874–878

    Article  PubMed  Google Scholar 

  56. Quiroz LH, Gutman RE, Shippey S, Cundiff GW, Sanses T, Blomquist JL, Handa VL (2008) Abdominal sacrocolpopexy: anatomic outcomes and complications with Pelvicol, autologous and synthetic graft materials. Am J Obstet Gynecol 198:557.e1–557.e4

    Article  Google Scholar 

  57. Anitua E, Sanchez M, Orive G (2010) Potential of endogenous regenerative technology for in situ regenerative medicine. Adv Drug Deliv Rev 62:741–752

    Article  PubMed  CAS  Google Scholar 

  58. Evans CH, Palmer GD, Pascher A, Porter R, Kwong FN, Gouze E, Gouze JN, Liu F, Steinert A, Betz O, Betz V, Vrahas M, Ghivizzani SC (2007) Facilitated endogenous repair: making tissue engineering simple, practical, and economical. Tissue Eng 13:1987–1993

    Article  PubMed  CAS  Google Scholar 

  59. Hodde JP, Badylak SF, Brightman AO, Voytik-Harbin SL (1996) Glycosaminoglycan content of small intestinal submucosa: a bioscaffold for tissue replacement. Tissue Eng 2:209–217

    Article  PubMed  CAS  Google Scholar 

  60. Voytik-Harbin SL, Brightman AO, Kraine MR, Waisner B, Badylak SF (1997) Identification of extractable growth factors from small intestinal submucosa. J Cell Biochem 67:478–491

    Article  PubMed  CAS  Google Scholar 

  61. Kim NN, Min K, Pessina MA, Munarriz R, Goldstein I, Traish AM (2004) Effects of ovariectomy and steroid hormones on vaginal smooth muscle contractility. Int J Impot Res 16:43–50

    Article  PubMed  CAS  Google Scholar 

  62. Moalli PA, Talarico LC, Sung VW, Klingensmith WL, Shand SH, Meyn LA, Watkins SC (2004) Impact of menopause on collagen subtypes in the arcus tendineous fasciae pelvis. Am J Obstet Gynecol 190:620–627

    Article  PubMed  CAS  Google Scholar 

  63. Moalli PA, Debes KM, Meyn LA, Howden NS, Abramowitch SD (2008) Hormones restore biomechanical properties of the vagina and supportive tissues after surgical menopause in young rats. Am J Obstet Gynecol 199:161–168

    Article  PubMed  CAS  Google Scholar 

  64. Pessina MA, Hoyt RF Jr, Goldstein I, Traish AM (2006) Differential effects of estradiol, progesterone, and testosterone on vaginal structural integrity. Endocrinology 147:61–69

    Article  PubMed  CAS  Google Scholar 

  65. Smith P (1993) Estrogens and the urogenital tract. Studies on steroid hormone receptors and a clinical study on a new estradiol-releasing vaginal ring. Acta Obstet Gynecol Scand Suppl 157:1–26

    PubMed  CAS  Google Scholar 

  66. Higgins EW, Rao A, Baumann SS, James RL, Kuehl TJ, Muir TW, Pierce LM (2009) Effect of estrogen replacement on the histologic response to polypropylene mesh implanted in the rabbit vagina model. Am J Obstet Gynecol 201:505–509

    Article  PubMed  Google Scholar 

  67. Boennelycke M, Christensen L, Nielsen LF, Everland H, Lose G (2011) Tissue response to a new type of biomaterial implanted subcutaneously in rats. Int Urogynecol J Pelvic Floor Dysfunct 22:191–196

    Article  Google Scholar 

  68. Takacs P, Zhang Y, Yavagal S, Candiotti K, Medina C (2010) Estrogen Inhibits Vaginal Smooth Muscle Cell Elastin Production: Potential Role in the Pathophysiology of Stress Urinary Incontinence (ICS-IUGA 2010 Abstracts). Int Urogynecol J Pelvic Floor Dysfunct 21:S420–S421

    Google Scholar 

  69. Goldstein SR, Nanavati N (2002) Adverse events that are associated with the selective estrogen receptor modulator levormeloxifene in an aborted phase III osteoporosis treatment study. Am J Obstet Gynecol 187:521–527

    Article  PubMed  CAS  Google Scholar 

  70. Manodoro S, Werbrouck E, Ozog Y, De Ridder D, Rizk DE, Deprest J (2011) Experimental evaluation of the effect of age, parity and hormonal status on surgical repair of fascial defects (IUGA 2011 Abstracts). Int Urogynecol J Pelvic Floor Dysfunct 22:S92–S92

    Google Scholar 

  71. DeLancey JO, Morgan DM, Fenner DE, Kearney R, Guire K, Miller JM, Hussain H, Umek W, Hsu Y, Ashton-Miller JA (2007) Comparison of levator ani muscle defects and function in women with and without pelvic organ prolapse. Obstet Gynecol 109:295–302

    Article  PubMed  Google Scholar 

  72. Dietz HP, Simpson JM (2008) Levator trauma is associated with pelvic organ prolapse. BJOG 115:979–984

    Article  PubMed  CAS  Google Scholar 

  73. Abramowitch SD, Feola A, Jallah Z, Moalli PA (2009) Tissue mechanics, animal models, and pelvic organ prolapse: a review. Eur J Obstet Gynecol Reprod Biol 144(Suppl 1):S146–S158

    Article  PubMed  Google Scholar 

  74. Collins CA, Olsen I, Zammit PS, Heslop L, Petrie A, Partridge TA, Morgan JE (2005) Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell 122:289–301

    Article  PubMed  CAS  Google Scholar 

  75. Montarras D, Morgan J, Collins C, Relaix F, Zaffran S, Cumano A, Partridge T, Buckingham M (2005) Direct isolation of satellite cells for skeletal muscle regeneration. Science 309:2064–2067

    Article  PubMed  CAS  Google Scholar 

  76. Sacco A, Doyonnas R, Kraft P, Vitorovic S, Blau HM (2008) Self-renewal and expansion of single transplanted muscle stem cells. Nature 456:502–506

    Article  PubMed  CAS  Google Scholar 

  77. Davila GW (2012) Optimizing safety and appropriateness of graft use in pelvic reconstructive surgery: introduction to the 2nd IUGA Grafts Roundtable. Int Urogynecol J 23(Suppl 1):S3–S6

    Article  PubMed  Google Scholar 

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Funding

This study was supported by the Danish National Advanced Technology Foundation

Conflicts of interest

M Boennelycke: None

S Gras: None

G Lose: Receives research support and/or works as a consultant for Contura, Phizer, Astellas and Johnson & Johnson.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Copenhagen University Hospital, Herlev, Denmark

    M. Boennelycke, S. Gras & G. Lose

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  1. M. Boennelycke
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  2. S. Gras
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  3. G. Lose
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Corresponding author

Correspondence to S. Gras.

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Boennelycke, M., Gras, S. & Lose, G. Tissue engineering as a potential alternative or adjunct to surgical reconstruction in treating pelvic organ prolapse. Int Urogynecol J 24, 741–747 (2013). https://doi.org/10.1007/s00192-012-1927-4

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  • DOI: https://doi.org/10.1007/s00192-012-1927-4

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