Local injection of bone marrow progenitor cells for the treatment of anal sphincter injury: in-vitro expanded versus minimally-manipulated cells.

Benedetta Mazzanti,Federica Pessina,Annalisa Borghini,Lara Ballerini,Elisabetta Weber,Riccardo Saccardi,Bruno Lorenzi,Margherita Boieri

doi:10.1186/s13287-016-0344-x

Abstract

BackgroundAnal 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.MethodsThirty-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.ResultsTreatment 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.ConclusionsIn 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.

Highlights

Anal incontinence is a disabling condition that adversely affects the quality of life of a large number of patients, mainly with anal sphincter lesions
Autologous local implantation of bone marrow (BM)-mononuclear cells (MNC) represents a novel strategy for the achievement of therapeutic angiogenesis and neovascularization in patients affected by peripheral arterial diseases [9,10,11]
In the present study we demonstrated, in a preclinical model, that minimally manipulated BM stem cells (MNC) were as effective as in-vitro expanded BM-mesenchymal stem cells (MSC) for the repair of anal sphincters after injury

Summary

Introduction

Anal incontinence is a disabling condition that adversely affects the quality of life of a large number of patients, mainly with anal sphincter lesions. BM-MNC (CD34+ and CD133+) are the most common BM cell types used in clinical trials for patients with acute myocardial infarction and ischemic cardiomyopathy over the last decade [12]. Another approach in regenerative medicine assumes ex-vivo expansion of mesenchymal progenitors to reach adequate numbers for surgical application [13, 14]. MSC isolated from BM can be transferred and/or expanded on appropriate biocompatible support before clinical use, mainly in the orthopedic field [15]

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Discussion

Conclusion