Table 1 Selected preclinical studies of MSCs transplantation for PFDs
Author/year | Animal/models | MSC sources | Method of injection/number of cells | Tracking of MSCs | Functional assessments | Main outcomes | Conclusions |
|---|---|---|---|---|---|---|---|
Lin et al. 2010 [38] | Rats/VD | Human ADSCs | Urethral or intravenous/1 × 106 | Labeled with BrdU and EdU | Conscious cystometry | Urinary voiding function improved, elastin and smooth muscle content increased and MSCs survival for at least 4 weeks. | Transplantation of ADSCs via urethral or intravenous injection was effective in the treatment and/or prevention of SUI in a preclinical setting |
Cruz et al. 2012 [57] | Rats/VD | Rat BM-MSCs | Intravenous/2 × 106 | Labelled with GFP | / | GFP + MSCs in the pelvic region both 4 and 10 days after VD; the total flux decreased from 4 to 10 days after VD and sham VD | Intravenous administration of MSCs could provide an effective route for cell-based therapy |
Sadeghi et al. 2015 [80] | Rats/VD | Human BM-MSCs | Periurethral or intravenous/1 × 106 | In situ hybridization; bioluminescence imaging | LPP test | LPP, connective tissue content and vascular density increased in periurethral or intravenous groups; no labeled cells were observed in urethras at 4, 10, and 14 days | Human MSCs restored urinary continence with an immediate and sustained effect in the VD model; MSCs remained at the site of periurethral injection for < 7 days |
Menachem- Zidon et al. 2019 [58] | Rats/posterior midline vaginal incision | Rat BM-MSCs | Intravenous or vaginal subepithelial/2 × 106 | Labeled with PKH-26 or GFP | / | The epithelial layer healed; systemically transplanted MSCs differentiate into endothelial cells; systemically transplanted MSCs form blood vessel structures | These findings pave the way to further studies of the potential role of MSCs transplantation in improving surgical outcome in women with PFD |
Salcedo et al. 2013 [81] | Rats/SP or PNC | Rat BM-MSCs | Intravenous (IV) or intramuscular (IM) into the anal sphincter/2 × 106 | Labelled with GFP | Anal pressure test; anal sphincter EMG | Anal sphincter pressure increased in IV and IM groups after SP, but not after PNC; sphincter EMG amplitude also increased in both groups, but frequency only increased in IV group | MSC treatment resulted in significant improvement in anal pressures after SP, suggesting that MSCs could be utilized to facilitate recovery after anal sphincter injury |
Salcedo et al. 2014 [82] | Rats/SP | Rat BM-MSCs | IM/5 × 105 or serial IV/5 × 105 daily for 6 consecutive days | Labelled with GFP | Anal pressure test | Both IM and IV MSC treatment after injury caused an increase in anal pressure sustained at 5 weeks | MSCs delivered intravenously and intramuscularly resulted in functional recovery |
Kuismanen et al. 2018 [83] | Rats/SP | Human ADSCs | Intramuscular into the external sphincter/3 × 105 | Labelled with PMP-50 | ARM | ARM pressure was significantly higher in ADSCs treatment groups; No difference in the sphincter muscle continuation between the groups | The ADSCs injection with both saline and Bulkamid is a promising nonsurgical treatment for acute anal sphincter injury |
Gautam et al. 2014 [102] | Rabbits/cryoinjured urethral model | Autologous ADSCs | Urethral/2 × 106 | Labeled with PKH26 | LPP test | LPP of the cell-implanted group was higher compared with control group; implanted PKH26-labeled ADSCs were immunohistochemically positive for myoglobin, SMA, and Pax7 antibodies | Implantation of ADSCs into cryoinjured rabbit urethras promoted the recovery of urethral function |