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

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Diseases of the Colon & Rectum

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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.

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Acknowledgment

The authors thank Professor Alison F. Brading (University Department of Pharmacology, Oxford, United Kingdom) for critical discussion and review of the manuscript.

Author information

Authors and Affiliations

  1. Department of Surgery, University of Siena, Viale Bracci, 53100, Siena, Italy

    Bruno Lorenzi M.D., Remo Vernillo M.D. & Marco Lorenzi M.D.

  2. Department of Biomedical Sciences, University of Siena, Siena, Italy

    Federica Pessina Ph.D. & Giampietro Sgaragli M.D.

  3. Molecular Medicine Section, Department of Neurosciences, University of Siena, Siena, Italy

    Paola Lorenzoni Ph.D. & Renato Gerli M.D.

  4. Bone Marrow Transplantation Unit, Department of Haematology, Careggi Hospital, Florence, Italy

    Serena Urbani B.S., Benedetta Mazzanti Ph.D., Alberto Bosi M.D. & Riccardo Saccardi M.D.

Authors
  1. Bruno Lorenzi M.D.
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  2. Federica Pessina Ph.D.
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  3. Paola Lorenzoni Ph.D.
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  4. Serena Urbani B.S.
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  5. Remo Vernillo M.D.
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  11. Marco Lorenzi M.D.
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Corresponding author

Correspondence to Bruno Lorenzi M.D..

Additional information

Supported by a grant from the University of Siena (PAR 2005).

Address of correspondence: Marco Lorenzi, M.D., Department of Surgery, University of Siena, Viale Bracci, 53100 Siena, Italy.

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Lorenzi, B., Pessina, F., Lorenzoni, P. et al. Treatment of Experimental Injury of Anal Sphincters with Primary Surgical Repair and Injection of Bone Marrow-Derived Mesenchymal Stem Cells. Dis Colon Rectum 51, 411–420 (2008). https://doi.org/10.1007/s10350-007-9153-8

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  • DOI: https://doi.org/10.1007/s10350-007-9153-8

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