Table 1.

Selected pre-clinical studies of secretome treatment for urological diseases

Study	Pathology	Stem Cell Type	Study Design	Major Conclusions
Dissaranan et al., 2014	SUI	MSCs, CCM	IV MSCs or peri-urethral CCM were administered after vaginal dilation. One week after injury, LPP and EUS EMG were measured.	LPP was significantly improved in both treatment groups, demonstrating that local injection of CCM provided a similar benefit to systemic cell therapy
Deng et al., 2015	SUI	MSCs, CCM	IV MSC or IP CCM were administered following vaginal distension and PN crush. Three weeks after injury, LPP and PN sensory branch potentials were measured.	LPP was significantly improved in both treatment groups, suggesting systemic administration of acellular secretome has similar efficacy to cell therapy
Bi et al., 2007	AKI	MSCs, CCM	MSCs or CCM were administered systemically after cisplatin-induced AKI in rats.	Both MSC and CCM treatment improved renal function and histology following acute renal injury when administered systemically.
Van Koppen et al., 2012	CKD	CCM	In a sub-total nephrectomy model of CKD, rats were intravenously injected with CCM or non-conditioned media. Renal function and histology were analyzed 6 weeks after treatment.	Treatment with CCM improved GFR significantly compared to control. CCM-treated rats had less tubular damage. CCM was effective in reversing chronic kidney damage.
Da Silva et al., 2015	CKD	MSCs, CCM	In a unilateral ureteral obstruction model of CKD, rats were administered IV MSC or CCM. Inflammatory cytokines and renal histology were analyzed.	In both treatment groups, levels of inflammatory cytokines were reduced. Histological analysis showed decrease fibrosis and apoptosis in both groups.
Zhang et al.,	DBD	ADSCs	DBD was induced in rats using a high fat diet and streptozocin. ADSCs were injected in the detrusor or via tail vein. Conscious cystometry was performed 1 month later to assess bladder function.	60% of rats receiving tail vein injections and 40% of rats receiving intra-detrusor injections demonstrated bladder dysfunction, compared to 100% in the control group. Only a fraction of injected ADSCs remained in the bladder, suggesting a paracrine effect.
Song et al., 2013	OAB	MSCs	Intra-detrusor (human) MSCs or IV solifenacin were administered to rats with OAB induced by urethral ligation. Cystometry was performed at 2 and 4 weeks.	Bladder parameters improved with MSC treatment and at 4 weeks surpassed those of the anti-muscarinic group. This effect occurs without engraftment of human MSCs.
Albersen et al., 2010	ED	ADSCs, ADSC lysate	Intracavernosal ADSCs or ADSC lysate were injected in a bilateral cavernosal nerve injury ED model. Erectile function was measured 4 weeks later by assessing intracavernosal pressure	Animals in both treatment groups had improved erectile function. In the stem cell group, only a small fraction of cells were observed in the cavernosal tissue after 1 month, suggesting a paracrine effect.
Sun et al., 2012	ED	MSC, CCM	Intracavernosal injections of MSCs or CCM were administered to rats with diabetes-induced ED. Erectile function was measured 4 weeks later by assessing intracavernosal pressure.	Both treatment groups experienced partial restoration of erectile function. Immunohistochemistry demonstrated increased staining of nNOS and NF fibers.

SUI: stress urinary incontinence, MSC: mesenchymal stem cells, CCM: conditioned culture media, LPP: leak point pressure, EUS: external urethral sphincter, EMG: electromyography, IV: intravenous, IP: intraparenchymal, PN: pudendal nerve, AKI: acute kidney injury, GFR: glomerular filtration rate, DBD: diabetic bladder dysfunction, OAB: overactive bladder, ED: erectile dysfunction, nNOS: nitric oxide synthase, NF: neurofilament