nach oben

Erschienen in:

01.04.2008 | Original Contribution

Treatment of Experimental Injury of Anal Sphincters with Primary Surgical Repair and Injection of Bone Marrow-Derived Mesenchymal Stem Cells

verfasst von: Bruno Lorenzi, M.D., Federica Pessina, Ph.D., Paola Lorenzoni, Ph.D., Serena Urbani, B.S., Remo Vernillo, M.D., Giampietro Sgaragli, M.D., Renato Gerli, M.D., Benedetta Mazzanti, Ph.D., Alberto Bosi, M.D., Riccardo Saccardi, M.D., Marco Lorenzi, M.D.

Erschienen in: Diseases of the Colon & Rectum | Ausgabe 4/2008

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Sphincter injury is a common cause of anal incontinence. Surgical repair remains the operation of choice; however, the outcome often is poor. We investigated the ability of injected bone marrow-derived mesenchymal stem cells to enhance sphincter healing after injury and primary repair in a preclinical model.

Methods

Twenty-four inbred Wistar Furth rats were divided into three groups. As a control, Group A underwent sham operation. Group B had sphincterotomy and repair of both anal sphincters plus saline injections. The study group (Group C) underwent sphincterotomy and repair followed by intrasphincteric injections of syngenic bone marrow-derived mesenchymal stem cells. A further group (Group D) of outbred Wistar rats treated with mesenchymal stem cells and immunosuppressive therapy also was evaluated. At 30 days, histologic and morphometric analysis and in vitro contractility testing was performed.

Results

A significant decrease of muscle tissue was observed at the site of repair after sphincter injury. However, in Groups C and D, histologic examination demonstrated new muscle fibers and morphometric analysis revealed a significantly greater muscle area fraction than in Group B (P < 0.05). Moreover, mesenchymal stem cells injection improved contractility of sphincters strips compared with Group B (P < 0.05). No significant differences were found between Groups C and D.

Conclusions

In our experimental model, bone marrow-derived mesenchymal stem cells injection improved muscle regeneration and increased contractile function of anal sphincters after injury and repair. Therefore, mesenchymal stem cells may represent an attractive tool for treating anal sphincter lesions in humans. Investigations into the biologic basis of this phenomenon should increase our knowledge on underlying mechanisms involved in sphincter repair.

Rothbarth J, Bemelman WA, Meijerink WJ, et al. What is the impact of fecal incontinence on quality of life? Dis Colon Rectum 2001;44:67–71.PubMedCrossRef

Whitehead WE, Wald A, Norton NJ. Treatment options for fecal incontinence. Dis Colon Rectum 2001;44:131–44.PubMedCrossRef

Oliveira L, Wexner SD. Anal incontinence. In: Beck DE, Wexner SD, eds. Fundamentals of anorectal surgery. London: WB Saunders Company Ltd., 1998:115–52.

Sultan AH, Kamm MA, Hudson CN, Thomas JM, Bartram CI. Anal-sphincter distruption during vaginal delivery. N Engl J Med 1993;329:1905–11.PubMedCrossRef

Varma A, Gunn J, Gardiner A, Lindow SW, Duthie GS. Obstetric anal sphincter injury: prospective evaluation of incidence. Dis Colon Rectum 1999;42:1537–43.PubMedCrossRef

Oberwalder M, Dinnewitzer A, Baig MK, et al. The association between late-onset fecal incontinence and obstetric anal sphincter defects. Arch Surg 2004;139:429–32.PubMedCrossRef

Lindsey I, Jones OM, Smilgin-Humphreys MM, Cunningham C, Mortensen NJ. Patterns of fecal incontinence after anal surgery. Dis Colon Rectum 2004;47:1643–9.PubMedCrossRef

Casillas S, Hull TL, Zutshi M, Trzcinski R, Bast JF, Xu M. Incontinence after a lateral internal sphincterotomy: are we underestimating it? Dis Colon Rectum 2005;48:1193–9.PubMedCrossRef

Karoui S, Leroi AM, Koning E, Menard JF, Michot F, Denis P. Results of sphincteroplasty in 86 patients with anal incontinence. Dis Colon Rectum 2000;43:813–20.PubMedCrossRef

10.

Malouf AJ, Norton CS, Engel AF, Nicholls RJ, Kamm MA. Long-term results of overlapping anterior anal-sphincter repair for obstetric trauma. Lancet 2000;355:260–5.PubMedCrossRef

11.

Halverson AL, Hull TL. Long-term outcome of overlapping anal sphincter repair. Dis Colon Rectum 2002;45:345–8.PubMedCrossRef

12.

Bravo Gutierrez A, Madoff RD, Lowry AC, Parker SC, Buie WD, Baxter NN. Long-term results of anterior sphincteroplasty. Dis Colon Rectum 2004;47:727–32.PubMedCrossRef

13.

Vaizey CJ, Norton C, Thornton MJ, Nicholls RJ, Kamm MA. Long-term results of repeat anterior anal sphincter repair. Dis Colon Rectum 2004;47:858–63.PubMedCrossRef

14.

Zorcolo L, Covotta L, Bartolo DC. Outcome of anterior sphincter repair for obstetric injury: comparison of early and late results. Dis Colon Rectum 2005;48:524–31.PubMedCrossRef

15.

Rosenthal N. Prometheus’s vulture and the stem-cell promise. N Engl J Med 2003;349:267–74.PubMedCrossRef

16.

Herzog EL, Chai L, Krause DS. Plasticity of marrow-derived stem cells. Blood 2003;102:3483–93.PubMedCrossRef

17.

LaBarge MA, Blau HM. Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury. Cell 2002;111:589–601.PubMedCrossRef

18.

Muguruma Y, Reyes M, Nakamura Y, et al. In vivo and in vitro differentiation of myocytes from human bone marrow-derived multipotent progenitor cells. Exp Hematol 2003;31:1323–30.PubMedCrossRef

19.

Bossolasco P, Corti S, Strazzer S, et al. Skeletal muscle differentiation potential of human adult bone marrow cells. Exp Cell Res 2004;295:66–78.PubMedCrossRef

20.

Santa María L, Rojas CV, Minguell JJ. Signals from damaged but not undamaged skeletal muscle induce myogenic differentiation of rat bone–marrow-derived mesenchymal stem cells. Exp Cell Res 2004;300:418–26.PubMedCrossRef

21.

Yokoyama T, Huard J, Pruchnic R, et al. Muscle-derived cell transplantation and differentiation into lower urinary tract smooth muscle. Urology 2001;57:826–31.PubMedCrossRef

22.

Yiou R, Dreyfus P, Chopin DK, Abbou CC, Lefaucheur JP. Muscle precursor cell autografting in a murine model of urethral sphincter injury. BJU Int 2002;89:298–302.PubMedCrossRef

23.

Cannon TW, Lee JY, Somogyi G, et al. Improved sphincter contractility after allogenic muscle-derived progenitor cell injection into the denervated rat urethra. Urology 2003;62:958–63.PubMedCrossRef

24.

Yiou R, Yoo JJ, Atala A. Restoration of functional motor units in a rat model of sphincter injury by muscle precursor cell autografts. Transplantation 2003;76:1053–60.PubMedCrossRef

25.

Peyromaure M, Sebe P, Praud C, et al. Fate of implanted syngenic muscle precursor cells in striated urethral sphincter of female rats: perspectives for treatment of urinary incontinence. Urology 2004;64:1037–41.PubMedCrossRef

26.

Kwon D, Minnery B, Kim Y, et al. Neurologic recovery and improved detrusor contractility using muscle-derived cells in rat model of unilateral pelvic nerve transaction. Urology 2005;65:1249–53.PubMedCrossRef

27.

Dobson KR, Reading L, Haberey M, Marine X, Scutt A. Centrifugal isolation of bone marrow from bone: an improved method for the recovery and quantitation of bone marrow osteoprogenitor cells from rat tibiae and femurae. Calcif Tissue Int 1999;65:411–3.PubMedCrossRef

28.

Brading AF, Sibley GN. A superfusion apparatus to study field stimulation of smooth muscle from mammalian urinary bladder. J Physiol 1983;334:11–2.

29.

Young CJ, Mathur MN, Eyers AA, Solomon MJ. Successful overlapping anal sphincter repair: relationship to patient age, neuropathy, and colostomy formation. Dis Colon Rectum 1998;41:344–9.PubMedCrossRef

30.

Gilliland R, Altomare D, Moreira H Jr, Oliveira L, Gilliland JE, Wexner SD. Pudendal neuropathy is predictive of failure following anterior overlapping sphincteroplasty. Dis Colon Rectum 1998;41:1516–22.PubMedCrossRef

31.

Norderval S, Öian P, Revhaug A, Vonen B. Anal incontinence after obstetric sphincter tears: outcome of anatomic primary repairs. Dis Colon Rectum 2005;48:1055–61.PubMedCrossRef

32.

Fitzpatrick M, Behan M, O’Connell PR, O’Herlihy C. A randomized clinical trial comparing primary overlap with approximation repair of third-degree obstetric tears. Am J Obstet Gynecol 2000;183:1220–4.PubMedCrossRef

33.

Tjandra JJ, Han WR, Goh J, Carey M, Dwyer P. Direct repair vs. overlapping sphincter repair: a randomized, controlled trial. Dis Colon Rectum 2003;46:937–43.PubMedCrossRef

34.

Pinta TM, Kylänpää ML, Salmi TK, Teramo KA, Luukkonen PS. Primary sphincter repair: are the results of the operation good enough? Dis Colon Rectum 2004;47:18–23.PubMedCrossRef

35.

Kairaluoma MV, Raivio P, Aarnio MT, Kellokumpu IH. Immediate repair of obstetric anal sphincter rupture: medium-term outcome of the overlap technique. Dis Colon Rectum 2004;47:1358–63.PubMedCrossRef

36.

Garcia V, Rogers RG, Kim SS, Hall RJ, Kammerer-Doak DN. Primary repair of obstetric anal sphincter laceration: a randomized trial of two surgical techniques. Am J Obstet Gynecol 2005;192:1697–701.PubMedCrossRef

37.

Leroi AM, Kamm MA, Weber J, Denis P, Hawley PR. Internal anal sphincter repair. Int J Colorectal Dis 1997;12:243–5.PubMedCrossRef

38.

Morgan R, Patel B, Beynon J, Carr ND. Surgical management of anorectal incontinence due to internal anal sphincter deficiency. Br J Surg 1997;84:226–30.PubMedCrossRef

39.

Kratchmarova I, Blagoev B, Haack-Sorensen M, Kassem M, Mann M. Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation. Science 2005;308:1472–7.PubMedCrossRef

40.

Togel F, Hu Z, Weiss K, Isaac J, Lange C, Westenfelder C. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am J Physiol Renal Physiol 2005;289:F31–42.PubMedCrossRef

41.

Natsu K, Ochi M, Mochizuki Y, Hachisuka H, Yanada S, Yasunaga Y. Allogeneic bone marrow-derived mesenchymal stromal cells promote the regeneration of injured skeletal muscle without differentiation into myofibers. Tissue Eng 2004;10:1093–112.PubMed

42.

Deasy BM, Jankowski RJ, Huard J. Muscle-derived stem cells: characterization and potential for cell-mediated therapy. Blood Cells Mol Dis 2001;27:924–33.PubMedCrossRef

43.

Cossu G, Mavilio F. Myogenic stem cells for the therapy of primary myopathies: wishful thinking or therapeutic perspective? J Clin Invest 2000;105:1669–74.PubMedCrossRef

Titel: Treatment of Experimental Injury of Anal Sphincters with Primary Surgical Repair and Injection of Bone Marrow-Derived Mesenchymal Stem Cells
verfasst von: Bruno Lorenzi, M.D.
Federica Pessina, Ph.D.
Paola Lorenzoni, Ph.D.
Serena Urbani, B.S.
Remo Vernillo, M.D.
Giampietro Sgaragli, M.D.
Renato Gerli, M.D.
Benedetta Mazzanti, Ph.D.
Alberto Bosi, M.D.
Riccardo Saccardi, M.D.
Marco Lorenzi, M.D.
Publikationsdatum: 01.04.2008
Verlag: Springer-Verlag
Erschienen in: Diseases of the Colon & Rectum / Ausgabe 4/2008
Print ISSN: 0012-3706
Elektronische ISSN: 1530-0358
DOI: https://doi.org/10.1007/s10350-007-9153-8

Neu im Fachgebiet Chirurgie

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

23.04.2024 Ablationstherapie Nachrichten

Nach der Katheterablation von Vorhofflimmern kommt es bei etwa einem Drittel der Patienten zu Rezidiven, meist binnen eines Jahres. Wie sich spätere Rückfälle auf die Erfolgschancen einer erneuten Ablation auswirken, haben Schweizer Kardiologen erforscht.

Hinter dieser Appendizitis steckte ein Erreger

23.04.2024 Appendizitis Nachrichten

Schmerzen im Unterbauch, aber sonst nicht viel, was auf eine Appendizitis hindeutete: Ein junger Mann hatte Glück, dass trotzdem eine Laparoskopie mit Appendektomie durchgeführt und der Wurmfortsatz histologisch untersucht wurde.

Mehr Schaden als Nutzen durch präoperatives Aussetzen von GLP-1-Agonisten?

23.04.2024 Operationsvorbereitung Nachrichten

Derzeit wird empfohlen, eine Therapie mit GLP-1-Rezeptoragonisten präoperativ zu unterbrechen. Eine neue Studie nährt jedoch Zweifel an der Notwendigkeit der Maßnahme.

Ureterstriktur: Innovative OP-Technik bewährt sich

19.04.2024 EAU 2024 Kongressbericht

Die Ureterstriktur ist eine relativ seltene Komplikation, trotzdem bedarf sie einer differenzierten Versorgung. In komplexen Fällen wird dies durch die roboterassistierte OP-Technik gewährleistet. Erste Resultate ermutigen.

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Aktuelle BDC Leitlinien-Webinare

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare

CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare

CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske

Dr. med. Benjamin Meyknecht

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare

CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2008

Stapled Technique for Acute Thrombosed Hemorrhoids: A Randomized, Controlled Trial with Long-Term Results

Outcome of Transanal Endoscopic Microsurgery and Adjuvant Radiotherapy in Patients with T2 Rectal Cancer

Is C-Reactive Protein a Prognostic Factor of Colorectal Cancer?

Overlap Technique Improves Results of Primary Surgery after Obstetric Anal Sphincter Tear

The Impact of Genomics on Colorectal Surgery in the First Half of the 21st Century: Musings on a Sad Seamstress and her Offspring

Endo–vacuum Assisted Closure Treatment for Rectal Anastomotic Insufficiency

Update Chirurgie