Stem-cell therapy for erectile dysfunction

Peer review under responsibility of Arab Association of Urology.

Figures & data

Table 1 An overview of preclinical SC studies targeting ED (adapted from [11]). The erectile function was improved in all studies.

Ref.	Pathophysiology	Type of SC	Time of evaluation	Tissue/molecular effects
[24]	CNI (rat)	Neuronal ESC	3 months	Improved neurofilament staining in dorsal and cavernous nerves. No evidence of incorporation of SCs
[25]	CNI (crush, rat)	MDSC	2 + 4 weeks	Increased cavernous level of axonal marker. Persistent LacZ expression (used as cell marker)
[26]	Ageing (rat)	BMSC or BMSC modified with eNOS	7 + 21 days	Cells expressing LacZ found in erectile tissue up to 21 days. Increased eNOS expression and activity, increased cGMP levels
[27]	Ageing (rat)	MDSC	2 + 4 weeks	Co-location of DAPI, α-smooth muscle actin and smoothelin Increased α-smooth muscle actin
[28]	CN resection (rat)	Bone marrow mononuclear fraction	3 + 5 weeks	Improved nNOS and eNOS levels, decreased apoptosis
[29]	Ageing (rat)	BMSC	3, 4 weeks, 3 + 4 months	Increased cGMP in CC, markedly dilated sinusoidal spaces in the CC
[30]	DM type II (rat)	ADSC	3 weeks	Increased nNOS levels in dorsal penile nerve endothelial cells in CC. No significant SC incorporation
[31]	Hyperlipidaemia (rat)	ADSC	4 weeks	Increased nNOS levels in dorsal penile nerve and endothelial cells in CC. No significant SC incorporation
[32]	CNI (crush, rat)	BMSC selected for p75 neurotrophin	4 weeks	Rare long-term engraftment of GFP-positive cells, showing mesenchymal morphology (no receptor expression or differentiation)
[21]	CNI (crush, rat)	ADSC or ADSC-derived lysate	4 weeks	Preservation of nNOS and smooth muscle content in the penis Prevention of cavernous fibrosis. No significant cell incorporation
[33]	Diabetes type I (rat)	BMSC	4 weeks	Increased smooth muscle and endothelial markers. Few CM-DiI (cell marker)-positive cells at 4 weeks co-located with smooth muscle and endothelial markers
[34]	CNI (crush, rat)	ADSC	1,3,7,28 days	Increased smooth muscle: collagen ratio in the erectile tissue + time-dependent increase in nNOS expression in dorsal nerve after intracavernous injection. Injected cells recruited to the MPG in injured rats, not in sham, soon after injury, but not permanently engrafted
[35]	CNI (crush, rat)	MDSC	4 weeks	Increased cGMP levels in penile tissue
[36]	CNI (crush, rat)	ADSC	2 or 7 days	Both autologous and allogeneic ADSCs exit the CC within days of injection and CNI; migrates preferentially towards bone marrow
[37]	Diabetes type I (rat)	BMSC	4 weeks	Increased smooth muscle and endothelial markers. Enhanced penile VEGF expression
[18]	CNI (crush, rat)	SVF	3 months	Improved nNOS and neurofilament staining in the dorsal penile nerve. Improved smooth muscle/collagen ratio in erectile tissue
[38]	Pelvic irradiation	ADSC	6 weeks	Improved nNOS expression in dorsal penile nerve and MPG, improved smooth muscle content, EdU (cell marker)-positive cells migrated into the MPG
[39]	CNI (crush, rat)	BMSC	4 weeks	Improved nNOS and eNOS levels
[22]	Diabetes type I (rat)	BMSC or BMSC-conditioned culture medium	4 weeks	In-vitro: secretion of neurotrophic molecules by BMSC. Invivo: improved nNOS and neurofilament staining in the dorsal penile nerve. Time-dependent decrease in number of BMSCs in CC after injection
[40]	CNI (crush, rat)	ADSC embedded in a BDNF membrane	4 weeks	Increased smooth muscle/collagen ratio, nNOS content, phospho-eNOS protein expression, and cGMP level
[41]	Diabetes type I (rat)	ADSC	4 weeks	This result absent after genetic knock-down of andromedullin Increased VE-cadherin and eNOS.
[23]	Diabetes type [1] SVF	2 weeks	This result absent after adding a VEGF blocker. Increased eNOS	(mouse) phosphorylation, and cGMP expression. Increased cavernous VEGF-A expression
[42]	CNI (crush, rat)	ADSC	3 months	Increased nNOS levels
[43]	CNI (crush, rat)	ADSC in NGF-hydrogel	4 weeks	Increased smooth muscle content, increased eNOS levels
[44]	CNI (crush, rat)	BMSC	4 weeks	Improved smooth muscle content, improved nNOS expression
[45]	CNI (crush, rat)	ADSC	4 weeks	Improved smooth muscle content

BDNF, bone-derived neurotrophic factor; VEGF, vascular endothelial growth factor.