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

Abstract

Anal incontinence is a devastating condition that significantly reduces the quality of life. Our aim was to evaluate the effect of human adipose stem cell (hASC) injections in a rat model for anal sphincter injury, which is the main cause of anal incontinence in humans. Furthermore, we tested if the efficacy of hASCs could be improved by combining them with polyacrylamide hydrogel carrier, Bulkamid. Human ASCs derived from a female donor were culture expanded in DMEM/F12 supplemented with human platelet lysate. Female virgin Sprague‐Dawley rats were randomized into four groups (n = 14–15/group): hASCs in saline or Bulkamid (3 × 105/60 μl) and saline or Bulkamid without cells. Anorectal manometry (ARM) was performed before anal sphincter injury, at two (n = 58) and at four weeks after (n = 33). Additionally, the anal sphincter tissue was examined by micro‐computed tomography (μCT) and the histological parameters were compared between the groups. The median resting and peak pressure during spontaneous contraction measured by ARM were significantly higher in hASC treatment groups compared with the control groups without hASCs. There was no statistical difference in functional results between the hASC‐carrier groups (saline vs. Bulkamid). No difference was detected in the sphincter muscle continuation between the groups in the histology and μCT analysis. More inflammation was discovered in the group receiving saline with hASC. The hASC injection therapy with both saline and Bulkamid is a promising nonsurgical treatment for acute anal sphincter injury. Traditional histology combined with the 3D μCT image data lends greater confidence in assessing muscle healing and continuity. Stem Cells Translational Medicine 2018;7:295–304

Perspectives for Clinical Translation of Adipose Stromal/Stem Cells

“…Moreover, the safety and efficacy of human ASCs have been demonstrated in animal models for the treatment of multiple sclerosis [160, 161], glioblastoma [162, 163], spinal fusion [164], chronic liver failure [165, 166], and acute kidney injuries [167, 168]. Furthermore, human ASCs have been successfully used in bone regeneration [73, 169, 170] and for the treatment of acute anal sphincter injuries [171]. The capacity of ASCs to cure inflammatory bowel diseases has been proven, both in vivo [10] and in phase III clinical trials.…”

MSC-based therapy in female pelvic floor disorders

“…Also, in both MSCs treated groups, less fibrosis and more collagen deposition were found, with the intravascular injection group showing the least scarring. Kuismanen et al [83] reported similar results of an increase in anal sphincter pressure after MSCs delivery in the same animal model. In addition, a biocompatible carrier, polyacrylamide hydrogel Bulkamid was found to be a suitable carrier for MSCs, because Bulkamid well integrated into the tissue, and a minor foreign body reaction was found in the group receiving Bulkamid with MSCs.…”

Stem cell therapy for faecal incontinence: Current state and future perspectives

“…Going further, Lane et al[ 49 ] performed a more aggressive injury defined as a “proctoepisiotomy”, but did not describe the technical details or extension. Similar or minor modified procedures have been employed by Mazzanti[ 60 ], Salcedo[ 75 ], Elmi[ 50 ], Pathi[ 42 ], Fitzwater[ 54 ], Montoya[ 57 ], Kuismanen[ 65 ] and Li[ 67 ].…”

“…The following publication was from Kuismanen et al[ 65 ] with Sprague-Dawley rats and with the novelty of employing xenogeneic human ASCs supplemented with human platelet lysate. For injury, the authors mimicked an acute fourth grade sphincter tear by sectioning both AS and anal mucosa, and then repaired them plane by plane with 6-0 poliglecaprone running sutures using magnifying loupes.…”