Treatment of experimental injury of anal sphincters with primary surgical repair and injection of bone marrow-derived mesenchymal stem cells.
OBJECTIVE
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.
Lorenzi
Bruno
B
Department of Surgery, University of Siena, Viale Bracci, 53100 Siena, Italy. lorenzi@unisi.it
Pessina
Federica
F
Lorenzoni
Paola
P
Urbani
Serena
S
Vernillo
Remo
R
Sgaragli
Giampietro
G
Gerli
Renato
R
Mazzanti
Benedetta
B
Bosi
Alberto
A
Saccardi
Riccardo
R
Lorenzi
Marco
M
D001003:Anal Canal / Q000293:injuries* / Q000473:pathology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D003082:Colectomy / Q000379:methods*; D004195:Disease Models, Animal; D007267:Injections; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009119:Muscle Contraction; D051381:Rats; D011920:Rats, Inbred WF; D012002:Rectal Diseases / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D016896:Treatment Outcome