Stem Cell Therapy in Bladder Dysfunction: Where Are We? And Where Do We Have to Go?

Table 1

Studies about stem cell therapy for bladder dysfunction.

Source	Mechanism of bladder dysfunction	Stem cell	Animal	Transplantation route	Tracking of stem cell	Bladder activity	Functional study	Smooth muscle differentiation	Remarks
Lee et al. [19]	BOO	Human BM-MSC	Rat	Direct transplantation into bladder	Iron oxide nanoparticle	Overactivity	UDS done: improvement of ICI, MVP, and RU	No	In vivo MRI examination for tracking MSC
Song et al. [20]	BOO	Human BM-MSC	Rat	Direct transplantation into bladder	None	Overactivity	UDS done: improvement of ICI and MVP	Yes	Transfection of human HGF gene into MSC
Woo et al. [21]	BOO	Mice BM-MSC	Mice	Intravenous injection	None	Overactivity	UDS done: improvement of capacity and compliance	No	Expression of chemokine CCL2
Tanaka et al.; [36]	BOO	BMD cell	Mice	Direct transplantation into BM	GFP labeling	Overactivity	UDS done: improvement of compliance and capacity	No	BOO was made by periurethral collagen injection, radiation was induced, and CCL2 induction increased.
Nishijima et al. [39]	BOO	BM cell	Rat	Direct transplantation into bladder	GFP labeling	Underactivity	UDS done: improvement of ICI and RU	Yes	Underactive model was created
Chen et al. [40]	Chronic ischemia by bilateral iliac artery ligation	BM-MSC	Rat	Intra-arterial injection	BrdU labeling	Underactivity	UDS done: improvement of ICI	No	Doxazosin mesylate was intragastrically administrated
Huang et al.; [41]	Chronic ischemia by hyperlipidemia	ADSC	Rat	Direct transplantation into bladder/intravenous injection	EdU labeling	Overactivity	UDS done: improvement of ICI and VV	Yes	Direct transplanted group showed better differentiation and better functional improvement
Zhang et al. [46]	Diabetes	ADSC	Rat	Direct transplantation into bladder/intravenous injection	EdU labeling	Overactivity. underactivity	UDS done: improvement of ICI and VV	No	Direct transplanted group showed better differentiation and better functional improvement
De Coppi et al. [54]	Cryoinjured	BM-MSC and AF-MSC	Rat	Direct transplantation into bladder	GFP labeling	N/A	N/A	Yes	Cell fusion in vitro
Huard et al. [56]	Cryoinjured	Muscle-derived cell	Mice	Direct transplantation into bladder	LacZ staining	Underactivity	Contractility test using muscle strip done: improvement of contractility	Yes	Ex vivo gene transfer using β-galactosidase
Sakuma et al. [57]	Cryoinjured	Adipocyte derived fat cell	Mice	Direct transplantation into bladder	GFP labeling	Underactivity	N/A	Yes	TGF-β signaling for smooth muscle differentiation
Nitta et al. [10]	Pelvic nerve injured	Sk-MSC	Rat	Damaged nerve lesion	GFP labeling	Underactivity	UDS done under electrical stimulation: improvement of IVP	Yes	Autologous and heterologous models were experimented together
Kwon et al. [11]	Pelvic nerve injured	Muscle-derived cell	Rat	Damaged nerve lesion	Enkephalin staining	Underactivity	UDS done under electrical stimulation: improvement of IVP	No	Autograft
Mitsui et al.; [49]	SCI	Neural stem cell	Rat	Damaged cord lesion	BrdU labeling	Overactivity	UDS done: improvement of VV and VP	No	No difference in the incidence of detrusor overactivity
Temeltas et al. [52]	SCI	Bone marrow stromal cell	Rat	Damaged cord lesion	E-NACM staining	Overactivity	UDS done: improvement of VV, RU and VP	N/A	Glial restricted precursor was also treated
Hu et al. [53]	SCI	Bone marrow stromal cell	Rat	Intravenous injection	BrdU labeling	Overactivity	UDS done: improvement of compliance and capacity	N/A	External urethral sphincter activity was checked

BOO: bladder outlet obstruction; SCI: spinal cord injury; MSC: mesenchymal stem cell; BMD: bone marrow derived cell; ADSC: adipose derived stem cell; AF-MSC: amniotic fluid derived mesenchymal stem cell; Sk-MSC: Skeletal muscle derived mesenchymal stem cell; UDS: urodynamic study; ICI: inter-contraction interval; MVP: maximal voiding pressure; RU: residual urine; VV: voided volume; VP: voiding pressure; IVP: intravesical pressure; GFP: green fluorescent protein.