Combination of laser and human adipose-derived stem cells in repair of rabbit anal sphincter injury: a new therapeutic approach

Abstract

BackgroundAnal sphincter injury leads to fecal incontinence. Based on the regenerative capability of laser and human adipose-derived stem cells (hADSCs), this study was designed to assess the effects of co-application of these therapies on anal sphincter recovery after injury.DesignMale rabbits were assigned to equal groups (n = 7) including control, sphincterotomy, sphincterotomy treated with laser (660 nm, 90 s, immediately after sphincterotomy, daily, 14 days), hADSCs (2 × 106 hADSCs injected into injured area of the sphincter immediately after sphincterotomy), and laser + hADSCs. Ninety days after sphincterotomy, manometry and electromyography were performed, sphincter collagen content was evaluated, and Ki67, myosin heavy chain (MHC), skeletal muscle alpha-actin (ACTA1), vascular endothelial growth factor A (VEGFA), and vimentin mRNA gene expression were assessed.ResultsThe laser + hADSCs group had a higher resting pressure compared with the sphincterotomy (p < 0.0001), laser (p < 0.0001), and hADSCs (p = 0.04) groups. Maximum squeeze pressure was improved in all treated animals compared with the sphincterotomized animals (p < 0.0001), without a significant difference between treatments (p > 0.05). In the laser + hADSCs group, motor unit numbers were higher than those in the laser group (p < 0.0001) but did not differ from the hADSCs group (p = 0.075). Sphincterotomy increased collagen content, but the muscle content (p = 0.36) and collagen content (p = 0.37) were not significantly different between the laser + hADSCs and control groups. Laser + hADSCs increased ACTA1 (p = 0.001) and MHC (p < 0.0001) gene expression compared with laser or hADSCs alone and was associated with increased VEGFA (p = 0.009) and Ki67 mRNA expression (p = 0.01) and decreased vimentin mRNA expression (p < 0.0001) compared with laser.ConclusionThe combination of laser and hADSCs appears more effective than either treatment alone for promoting myogenesis, angiogenesis, and functional recovery after anal sphincterotomy.

A systematic review of translation and experimental studies on internal anal sphincter for fecal incontinence

“…Several translation studies have revealed the molecular mechanism of SMC in IAS as intrinsic properties, which can be characterized by Ca 2+ , RhoA/ROCK, AAID, oxidative stress, RAS, COX, and inhibitory NTM. However, we observed that previous cellular treatments [ 16 - 20 , 79 ] did not show a relationship between SMCs-related histologic or functional outcomes and basal tone or relaxation-related molecular pathways in injured IAS regardless of the cell type or confirmation of IAS-incontinence. We considered that it might be due to the complexity of the molecular mechanisms for basal tone and relaxation of IAS as intrinsic properties ( Fig.…”

“…But it remained weak and unclear for an association between functional improvement of resting pressure and the differentiation of myoblasts into SMCs of IAS. Sarveazad et al [ 79 ] reported the efficacy of co-application of laser and hASC therapy showing improved resting anal pressure and enhanced myogenesis and angiogenesis with increased expression level. All the previous incontinence models included incision of EAS or adding pudendal nerve crush [ 16 - 20 , 79 ].…”

“…Sarveazad et al [ 79 ] reported the efficacy of co-application of laser and hASC therapy showing improved resting anal pressure and enhanced myogenesis and angiogenesis with increased expression level. All the previous incontinence models included incision of EAS or adding pudendal nerve crush [ 16 - 20 , 79 ]. In the observed histologic augmentation of smooth muscular layers in IAS, but in cell tracking, no newly differentiated SMCs of implanted stem cells were found at the injury site under fluorescence in situ [ 16 ], micro-computed tomography [ 19 ], confocal microscopy, or immunofluorescence assay using green fluorescent protein labeling [ 17 , 18 ] ( Table 2 ).…”

Combined application of chondroitinase ABC and photobiomodulation with low-intensity laser on the anal sphincter repair in rabbit

“…Sphincterotomy was performed based on the fourth degree rupture of the 1999 Sultan classification [external anal sphincter (EAS), internal anal sphincter (IAS), and anal mucosa tear] [ 28 ]. As in our previous study [ 12 ], after anesthesia with ketamine (80 mg/kg) and xylazine (10 mg/kg) in all rabbits, sphincterotomy in lithotomy position after disinfection of anus and perineal area of the left side of sphincter was performed at a depth of 1 cm.…”

Mesenchymal Stem Cells in Gastric Cancer: Vicious but Hopeful

“…Over time, other surface antigens, like CD271, STRO-1, CD106 and CD146 come to be accepted and recognized for MSC identification (18,19). MSC used to arouse excitement for regenerative medicine owing to they can quickly engraft to inflammatory cytokines or chemoattractant gradients produced by injured tissue and organs to exhibit their tissue healing functions, alone or in combination with other methods (20,21). With the hypothesis "tumor equates wound that never heals" arises, the function of MSC in tumors has been realized to parallel the role of MSC in wound healing that actively promotes MSC from bone marrow or adjacent tissues to mobilize into the TME (22,23).…”