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

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.

Evaluation of anatomical and functional results of overlapping anal sphincter repair with or without the injection of bone marrow aspirate concentrate: a case–control study

“…This theory was confirmed by the findings of Mazzanti et al . who concluded that mononuclear cells of the bone marrow and mesenchymal stem cells are equally effective as an adjunct to primary repair for the management of anal sphincter injuries in the animal model.…”

“…Alternatively, Mazzanti et al . have demonstrated in a preclinical model on rats that minimally manipulated bone marrow mononuclear cells are as effective as in vitro expanded mesenchymal stem cells for the recovery of anal sphincter injury.…”

“…The high cost and the advanced laboratory and technical efforts required for the preparation of ex vivo cultivated stem cells could limit their clinical application in humans [15]. Alternatively, Mazzanti et al [16] have demonstrated in a preclinical model on rats that minimally manipulated bone marrow mononuclear cells are as effective as in vitro expanded mesenchymal stem cells for the recovery of anal sphincter injury.…”

Mesenchymal Stromal Cells Anno 2019: Dawn of the Therapeutic Era? Concise Review

“…For most immunological disorders, intravenous administration has been the route of choice whereas for bone repair purposes, MSCs are seeded on transplantable scaffolds or administered as in vitro generated cartilaginous templates that undergo osteogenic differentiation after implantation . For treatment of other types of tissue injuries, MSCs have been applied into the wound area via local injections .…”

Functional Outcome of Human Adipose Stem Cell Injections in Rat Anal Sphincter Acute Injury Model

“…Recently Fitzwater et al noticed that the administration of rat myogenic stem cells enhanced the contractile function of the sphincter without significant changes in histologic morphology, which addresses the paracrine processes in stem cell therapy 14. To simplify the cell isolation and proliferation process, Mazzanti et al used freshly isolated minimally manipulated bone‐marrow derived mononuclear cells without expansion and found them to be as effective as in vitro expanded BM‐MSCs in the recovery of iatrogenic anal sphincter rupture 38. Muscle‐derived stem cell injections have been used in small pilot studies in women and the results are promising 39, 40, 41.…”