title: Local injection of bone marrow progenitor cells for the treatment of anal sphincter injury: in-vitro expanded versus minimally-manipulated cells.
abstract: BACKGROUND
  Anal incontinence is a disabling condition that adversely affects the quality of life of a large number of patients, mainly with anal sphincter lesions. In a previous experimental work, in-vitro expanded bone marrow (BM)-derived mesenchymal stem cells (MSC) were demonstrated to enhance sphincter healing after injury and primary repair in a rat preclinical model. In the present article we investigated whether unexpanded BM mononuclear cells (MNC) may also be effective.
  
  
  METHODS
  Thirty-two rats, divided into groups, underwent sphincterotomy and repair (SR) with primary suture of anal sphincters plus intrasphincteric injection of saline (CTR), or of in-vitro expanded MSC, or of minimally manipulated MNC; moreover, the fourth group underwent sham operation. At day 30, histologic, morphometric, in-vitro contractility, and functional analysis were performed.
  
  
  RESULTS
  Treatment with both MSC and MNC improved muscle regeneration and increased contractile function of anal sphincters after SR compared with CTR (p < 0.05). No significant difference was observed between the two BM stem cell types used. GFP-positive cells (MSC and MNC) remained in the proximity of the lesion site up to 30 days post injection.
  
  
  CONCLUSIONS
  In the present study we demonstrated in a preclinical model that minimally manipulated BM-MNC were as effective as in-vitro expanded MSC for the recovery of anal sphincter injury followed by primary sphincter repair. These results may serve as a basis for improving clinical applications of stem cell therapy in human anal incontinence treatment.
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134, Florence, Italy. benedetta.mazzanti@unifi.it.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Mazzanti
authors.affiliation: Upper GI Service, Mid Essex Hospital Services NHS Trust, Broomfield Hospital, Chelmsford, UK.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lorenzi
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Borghini
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134, Florence, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Boieri
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134, Florence, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Ballerini
authors.affiliation: Cell Therapy and Transfusion Medicine Unit, Careggi University Hospital, Florence, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Saccardi
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Weber
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Pessina
mesh_terms: D001003:Anal Canal / Q000293:injuries / Q000601:surgery*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology; D004195:Disease Models, Animal; D005242:Fecal Incontinence / Q000503:physiopathology / Q000628:therapy*; D017930:Genes, Reporter; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000502:physiology / Q000637:transplantation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D012038:Regeneration / Q000502:physiology; D016717:Sphincterotomy, Endoscopic
keywords: Anal incontinence; Anal sphincter injury; Anal sphincter repair; Bone marrow mesenchymal stem cells; Bone marrow mononuclear cells