Table 1.
The basic characteristics of included studies
| Study model | Cell type | Scaffold | Surgical approach | Size of implanted construct | Follow-up/study period | Outcome measure | Limitations | Reference No. |
|---|---|---|---|---|---|---|---|---|
| Male New Zealand white rabbit | Rabbit foreskin epidermal cells | Rabbit BAM | Tubularised | 1.5 cm × 1 cm (length) × (width) | 6 months | Retrograde urethrogram/histology/immunocytochemistry | Adaptation of implanted epidermal cells into urethral environment is quite lengthy | [7] |
| Male white rabbit | Rabbit epidermal cells | Rabbit BSM | Tubularised | 1.5 cm (length) | 12 months | Histology/immunocytochemistry/urethrography | – | [75] |
| – | – | DF-assembled scaffold | Human urothelial cells | – | 28 days | Histology/cell viability/mechanical test/western blot | – | [61] |
| – | Rabbit urethral epithelial cells | Surface-modified non-knitted PLLA | – | – | 48 h | Electron microscope | – | [30] |
| – | Human keratinocytes and fibroblasts | PLGA | – | – | 3 months | Simple sterility test/scanning electron microscope/histology/biodynamic analysis/MTT assay | – | [33] |
| – | Human urothelial cells | Human amniotic membrane/PLCL | – | – | 14 days | Live/dead staining/water-soluble tetrazolium salts measurement/immunostaining | – | [51] |
| – | Human urothelial cells | Fibroblast- based self-assembled scaffold | Tubularised | – | 14 days | Histology/immunofluorescence, real-time PCR analysis, electron microscopy, permeation studies | – | [66] |
| Rabbit | Rabbit corporal smooth muscle cells and lingual keratinocytes | Porcine acellular corpus spongiosum matrices | – | – | 6 months | Retrograde urethrography/histochemical analysis | – | [37] |
| – | Human urothelial cells (HUCs) | Fibroblast-based self assembled scaffold | Tubularised | – | 14 days | Histology, immunofluorescence, real-time PCR analysis, electron microscopy, permeation studies | [66] | |
| Female Mongrel dog | Dog urethral epithelial cells and smooth muscle cells | Dog ABM | Tubularised | 3.0 cm (length) | 11 months | Retrograde urethrography/histopathological examination | Small number of dogs included/use of dog rather than rabbit as study model | [74] |
| Male New Zealand rabbi | Smooth muscle cells | BSM | Onlay |
0.5 cm × 3.5 cm patch |
3 months | Urethroscope/histological/immunochemical analysis | – | [45] |
| – | Rabbit oral keratinocytes and TGF-β1 siRNA transfected fibroblasts | BAMG | – | – | 7 days | Enzyme-linked immunosorbent assay/histology/scanning electron microscope assay | – | [72] |
| Male Beagle dog | Dog smooth muscle cells and urothelial cells | Porcine ABM | Tubularised | 6.0 cm (length) | 12 months | Retrograde and voiding computed urethrocystography/histology/immunohistochemical analysis | Small number of experimental animals evaluated each time point | [14] |
| Female beagle dog | Dog bladder urothelial cells | Silk fibroin | Onlay | 3 × 1 cm2 | 6 months | Scanning electron microscope/histology/immunohistochemical staining/retrograde urethrography | Sample size was not sufficiently large | [48] |
| Male New Zealand rabbit | Rabbit skeletal muscle and hUCMSC | Muscle patch | Onlay | 0.5 cm × 0.5 cm round patch | 3 months | Histopathology/urethroscope/ureterography analysis | Absence of the corpora spongiosum in the reconstructed urethra | [70] |
| Male New Zealand rabbit | Rabbit epithelial differentiated adipose derived stem cells | BAMG | Onlay | 2.0 cm × 0.8 cm (length × width) | 6 months | Retrograde urethrography/immunofluorescent/western blot/microscopic image analysis | In vitro epithelial induction need to be optimise to reach the mature epithelial differentiation of ASCs | [27] |
| Male New Zealand rabbit | – | Bi-layer silk fibroin | Onlay |
1.0 cm × 2.0 cm patch |
3 months | Retrograde urethrography/histology/immunohistochemistry/histomorphometric analysis | [3] | |
| Male New Zealand rabbit | Rabbit urethral epithelial cells | Denuded human amniotic scaffold | Onlay |
0.5 cm × 1.0 cm patch |
3 months | Histological/immunohistochemical analysis | Application of denuded human amniotic membrane seeded with rabbit urethral epithelium cells restricts initiation of human based investigations/longer follow-up period was required to reveal latent adverse effects and complications | [35] |
| – | – | Df and adipose derived stem cell base self assembled scaffold | – | – | 10 weeks | Histology/immunohistochemistry burst pressure, suture strength, failure load, elastic modulus, failure strain | – | [62] |
| Male chinchilla rabbit | Rabbit keratinocyte | Sponge + collagen gel containing human or rabbit fibroblast | Onlay | – | 3 months | Histological analysis | – | [7] |
| Male New Zealand rabbit | – | BSM + autologous urethral tissue | Onlay |
0.5 cm × 2.5 cm patch |
3 months | Retrograde urethrography/immunohisto-chemical/histological analysis | Small number of study rabbits/short follow-up period/lack of penile curvature evaluation to confirm sufficient elasticity to maintain erection/lack of uroflowmetry/lack of anatomic analysis with cystoscopy | [44] |
| – | Dog urothelial cells | Hybrid PCL/PLLA | – | – | 14 days | 3-(4,5-Dimethylthiazole-2,5-di-phenyltetrazolium bromide (MTT)/scanning electron microscope/histology/immunohisto-chemical analysis | – | [42] |
| Male New Zealand rabbit | Rabbit epithelial | ICG-001 delivering collagen-P(LL-CL) | Tubularised | 2.0 cm × 1.0 cm (length × width) | 3 months | Urethrography/histology/immunohisto-logical analysis | More appropriate animal model is needed to evaluate the treatment outcomes for the post-traumatic urethral stricture | [43] |
| – | Rabbit urothelial cells and smooth muscle cells | PCL/PLCL | Tubularised | 2.0 cm | 7 days | MTS assay/live, dead assay and immunohistochemistry | – | [59] |
| Nude athymic male rat | Bone marrow derived mesenchymal stem cells and CD34 + HSPC | Poly(1,8-octanediol-co-citric acid) | Onlay | 2 mm × 8 mm × 0.15 mm | 28 days | Immunohistochemistry, bright field and polarised microscope images, Picrosirius staining | limited information was collected only from specific aspects of the innate immune system | [23] |
| Male New Zealand rabbit | Undifferentiated human amniotic mesenchymal stem cells | Hybrid PLLA/PEG | Onlay |
1.5 cm × 2.0 cm patch |
3 months | Histology/immunohistochemistry/retrograde urethrography analysis | Unknown mechanism of hAMSCs-based urethral regeneration | [34] |
| Male New Zealand rabbit | – | Rat-tail collagen type I | Tubular | 2 cm | 9 months | Scanning electron microscopy/histology/immunohistochemistry | – | [38] |
| New Zealand white male rabbit | Autologous rabbit urine stem cells | Small intestinal submucosa | Onlay | 2 cm | 3 months | Retrograde urethrogram/histological analysis/immunohistochemistry | The bioactive factors secreted by urine stem cells that might play role in tissue regeneration were not analysed, urethral defects were created in healthy animals and the number of experimental animals was not sufficient. | [47] |
| Male New Zealand white rabbit | Rabbit mesothelial cells | Autogenous tissue granulated silastic tube | Tubularised | 2.0 cm | 6 months | Retrograde urethrography/histology/immunohisto-chemistry | Urethral defect was created in healthy urethra, small number of experimental animal, using of small animal which is not clinically informative and potential risk of pyogenic infection development | [12] |
| Male beagle dog | Dog’s adipose derived stem cells and oral mucosal epithelial cells | Fibroblast based self-assembled scaffold | Tubularised | 2.0 cm | 3 months | MRI/Retrograde urethrogram/histology/prussian blue staining/immunohisto-chemistry | Complicated and time consuming procedures, short follow up period, short-segment urethral reconstruction | [69] |
| Male New Zealand white rabbit | Bi-layer silk fibroin scaffold | Onlay | 5 mm × 10 mm (length × width) | 3 months | Urethroscopy, retrograde urethroplasty, histological and immunohisto-chemical analyses | Small number of rabbits, short-term implantation period and lack of functional assessment | [49] | |
| New Zealand white rabbit | Rabbit adipose derived stem cells | Silk fibroin | Onlay | 2.5 cm × 1 cm | 6 weeks | Urethrography/histology/ | – | [50] |
| – | Human urothelial cells | DF and adipose derived stem cell based self assembled scaffold | – | – | 21 days | Histology/immunohistochemistry/mechanical testing/scanning electron microscopy | – | [64] |
| – | Porcine urothelial cells | Df based self assembled scaffold | – | – | 7 days | Histology/immunohistochemistry/permeability test/mechanical test/ | – | [63] |
| Human (all suffering from lichen sclerosus) | Human buccal mucosa keratinocyte and fibroblast | Human de-epidermised dermis | Onlay | 9.0–11.0 cm (various length in different patients) | 32–37 months (mean: 33.6 months) | Cystoscopy | – | [13] |
| Human | Human muscle and epithelial cell | Polyglycolic acid:poly(lactide-co-glycolide acid) | Tubularised | 4.0–6.0 cm (length) | 72 months | Histology/immunohistochemistry/urine analysis/cystourethroscopy/cystourethrography/flow measurement | – | [5] |
| Male athymic mouse | Human umbilical vein endothelial cells | Fibroblast based self-assembled scaffold | Tubularised | 28 days | Histology, immunostaining | – | [68] |
ABM acellular bladder matrix, BAM bladder acellular matrix, BAMG bladder acellular matrix graft, BSM bladder submucosal matrix, DF dermal fibroblast, PEG poly ethylene glycol, PLC poly-l-lactide-co-ε-caprolactone, PLGA polylactic-co-glycolic acid, PLLA poly-l-lactic acid