Table 1.

Current studies utilizing stem cells in various capacities for bladder bioengineering or regeneration.

Bladder Tissue Layer	Cell Source or Growth Factor	Model System	Major Findings	Reference(s)
Urothelium	Human bone marrow-derived mesenchymal stem cells (MSCs)	In vitro co-culture with human urothelial cells or urothelial cell conditioned medium	Induced urothelial-like cells that express cytokeratins typical of urothelium	[21]
			Exhibited epithelial characteristics via TEM
		In vitro co-culture with human urothelium or culture in urothelial cell conditioned medium	Induced urothelium that expressed urothelial markers Uroplakin Ia (UPIa) and cytokeratins 7 and 13	[22]
	Adipose-derived stem cells (ASCs)	In vitro co-culture with human urothelial cells or urothelial cell conditioned medium	Induction of uroplakin-expressing urothelial cells in vitro	[23,24,25]
		ASCs mixed with human urothelial cell line and implanted subcutaneously into athymic mice	High expression of UPIa and Uroplakin II(UPII) at 4 weeks post-implant	[26]
	Urine-derived stem cells (USCs)	In vitro culture in urothelial specific medium and in vivo implantation of induced urothelial cells	High expression of Uroplakins in induced urothelium in vitro and in vivo	[27,28,29]
			Barrier function in vitro
			Stratified layers of induced urothelium in vivo
	Human amniotic fetal stem cells	In vitro co-culture with bladder cancer cell conditioned medium	Morphologically resemble urothelial cells and express UPII, cytokeratin 8 and Fibroblast growth factor 10 (FGF10)	[30]
	Human umbilical cord-derived mesenchymal stromal cells (HUMSCs)	In vitro co-culture with urothelial cell conditioned medium	Morphologically resemble urothelial cells and express UPII and cytokeratins	[31]
		HUMSCs seeded on BAMGs were used to repair bladder defects in vivo using a canine transplant model	Bladder acellular matrix grafts (BAMGs) seeded with HUMSCs had better urothelial and muscle regeneration than did non-seeded grafts	[32]
	Human embryonic stem cells (ESCs)	In vitro culture through definitive endoderm (DE) intermediary step, then induction to urothelial cells with urothelial cell-specific medium	Expression of proteins involved in urothelial fate specification during induction	[33]
			High production of urothelium determined by uroplakin expression
	Induced pluripotent stem cells (iPSCs)	In vitro culture through DE intermediary step, then induction to urothelial cells with urothelial cell-specific medium	High production of urothelium determined by uroplakin expression	[33,34]
		Urinary tract-derived iPSCs cultured in vitro culture with urothelial cell conditioned medium	Differentiation of urothelial cells expressing UPs, cytokeratins and claudins	[35]
Muscle	Adipose-derived stem cells (ASCs)	In vitro culture in smooth muscle differentiation medium	Induced SMCs exhibited upregulation of smooth muscle proteins and contraction/relaxation properties in vitro	[36]
	Human bone marrow-derived MSCs	In vitro differentiated smooth muscle cells (via co-culture with human bladder SMCs or conditioned medium from the SMCs) were seeded onto scaffolds and transplanted in vivo	Induced smooth muscle cells increased expression of desmin in vivo and improved contractility in seeded grafts versus non-seeded grafts in vitro	[22]
		Poly (1,8-octaneodiol-co-citrate) elastomeric scaffolds were seeded with MSCs and transplanted onto cystectomized rat bladders	MSCs differentiated into SMCs within the graft and formed more organized muscular networks than did non-MSC seeded grafts	[37,38]
	Urine-derived stem cells (USCs)	USCs induced into SMCs via conditioned medium in vitro then seeded onto cellulose scaffolds and implanted subcutaneously in athymic mice	Increased SMC marker expression and functional contraction in vitro	[27,29]
			3D formation of bladder tissue in vivo
	Hair follicle stem cells	BAMGs seeded with hair follicle stem cells in vitro then transplanted to the rat bladder	Seeded grafts showed better muscle regeneration than did non-seeded grafts	[39]
	Muscle-derived stem cells	Small intestinal submucosa (SIS) scaffolds seeded with muscle-derived stem cells were cultured in vitro	Seeded grafts exhibited spontaneous contractile activities in vitro	[40]
Blood Vessels	Vascular endothelial growth factor (VEGF)	BAMGs were hydrated with various concentrations of VEGF and utilized in a porcine model of bladder augmentation	Significant increase in vascularization, epithelialization and muscle regeneration in vivo in VEGF-hydrated BAMGs	[41]
		BAMGs seeded with VEGF-loaded nanoparticles were transplanted onto bladders of rabbits after partial cystectomy	VEGF-loaded BAMGs showed significant increase in microvessel density with decreased rate of graft contracture	[42]
	Platelet-derived growth factor-BB (PDGF-BB) + VEGF	Porcine BAMGs were loaded with Platelet derived growth factor-BB (PDGF-BB) and VEGF and transplanted into rabbits after partial cystectomy	Porcine BAMGs loaded with PDGF-BB and VEGF improved smooth muscle regeneration, vascularization and contractility	[43]
	Adipose-derived endothelial progenitor cells (ADEPCs)	ADEPCs were isolated from rat adipose tissue and cultured in vitro	ADEPCs expressed endothelial cell markers and formed capillary-like structures in BAMGs	[44]
	CD34+ hematopoietic stem/progenitor cells (HPSCs) + Bone marrow-derived MSCs	CD34+ HPSCs and MSCs were seeded onto poly (1,8-octaneodiol-co-citrate) elastomeric scaffolds and transplanted onto rat bladders after partial cystectomy	CD34+ HSPCs and MSCs increased vascularization of grafts and induced de novo vascularization and peripheral nerve growth	[37]
	VEGF-expressing endothelial progenitor cells (EPCs)	BAMGs were seeded with EPCs modified to express VEGF and used in a porcine model of partial cystectomy and transplantation	Seeded BAMGs showed enhanced vascularization versus non-EPC/VEGF seeded grafts	[45]