Status, challenges, and future prospects of stem cell therapy in pelvic floor disorders

Table 1 The types of stem cells used for pelvic floor disorders treatment

No.	Cell type	Model	Transplantation method	Function	Results	Ref.
1	BMSCs	SUI animals	Periurethral injection	Differentiation into striated muscles and peripheral nerves cells	Restored the defected external urethral sphincter; Improved the symptoms of SUI and alleviated LPP	Corcos et al[17]; Kinebuchi et al[18]
2	HUMSCs	Sprague-Dawley rats	HUMSCs and SMCs combined with meshes transvaginally implanted into Sprague-Dawley rats	Anti-inflammatory effects and vascularization	A high collagen I/III ratio; Maturation of scar tissue during the wound healing stage	Ding et al[20]
3	EMSCs	POP rats	Subcutaneous tissue transplantation of EMSCs combined with meshes	Induction of collagen generation and arrangement; Enhancing mesh tension; Inhibition of FBS and recruitment of M2 macrophages	Improved the symptoms of SUI; Neo-tissue regeneration in POP repair	Edwards et al[25]; Paul et al[26]
4	ADMSCs	SUI rat model	Transplantation of ADMSCs into SUI rat model	Differentiation into muscle cells; Differentiation into fibroblasts and myeloblasts	Significant treatment of SUI; Strengthened tissue structure repair; Increased leak point pressure and maximum bladder capacity	Caplan et al[27]; Wu et al[29]; Fu et al[30]
5	MDSCs	Clinical trials of patients with SUI	Transurethral injection of MDSCs into urethral rhabdosphincter	NA	Patients exhibited improvement of SUI and reached a 75% success rate, without short or long-term adverse events	Stangel-Wojcikiewicz et al[35]; Carr et al[36]
6	hiPSCs	SUI rats	MACS-sorted pSMCs and ESC/iPSC-derived pSMCs injected periurethrally into SUI rats	Increasing tissue contents of elastin and collagen III and improving LPP values	Facilitated the functional recovery and restoration of sphincter structure in SUI rats, without tumor or teratoma formation or abnormal histology	Li et al[41]
7	USCs	Athymic mice	VEGF-expressing UDSCs mixed with human umbilical vein endothelial cells subcutaneously implanted into athymic mice	High differentiation, self-renewal, and anti-urine toxicity; Neovascularization, nerve regeneration and myogenic differentiation were enhanced by VEGF in vivo	75% USCs were safely persevered in urine over 24 h; Stem cell characteristics were retained; Potential use in genitourinary reconstruction	Lang et al[44]; Wu et al[45]

BMSCs: Bone marrow-derived mesenchymal cells; SUI: Stress urinary incontinence; HUMSCs: Human umbilical cord mesenchymal stem cells; SMC: Smooth muscle cell; EMSCs: Endometrial mesenchymal stem cells; POP: Pelvic organ prolapse; ADMSCs: Adipose-derived mesenchymal stem cells; MDSCs: Muscle-derived stem cells; NA: Not available; hiPSCs: Human induced pluripotent stem cells; MACS-sorted pSMCs: Muscle progenitor cells derived from human-induced pluripotent stem cells; ESC: Embryonic stem cells; iPSC: Induced pluripotent stem cells; USCs: Urine-derived stem cells; VEGF: Vascular endothelial growth factor.

Table 2 Clinical trials of stem cells used for pelvic floor disorders treatment

No.	Cell type	Patients	Transplantation method	Follow-up	Complications	Results	Ref.
1	ADMSCs	5 patients with SUI	Transurethral injection	1 yr	No severe complications reported	3 patients with a negative cough test; 40% patients satisfied with the treatment; The 24-h pad test also showed improvement	Kuismanen et al[31]
2	MDSCs	16 patients with SUI	Injection into the urethral sphincter	1 yr	No severe complications reported	50% continence; 25% some improvement; 25% no improvement	Stangel-Wojcikiewicz et al[35]
3	MDSCs	8 patients with SUI	Transurethral injection	Mean follow-up of 16.5 mo	No serious adverse events reported	62.5% improvement in SUI by the diary and pad weight test; 1 case of total continence; Cure or improvement continued for a median of 10 mo; 2 continued to have stress episodes and positive pad weight tests	Carr et al[36]
4	MDSCs	12 patients with SUI	Intrasphincteric injections	1 yr	1 case of occasional episodes of UTI; No other adverse events	25% dry; 7 patients improved in the pad test; 50% quality of life improved; 2 patients slightly worsened	Surcel et al[37]
5	MDSCs	20 patients with SUI	Injection into the urethral submucosa and rhabdosphincter	2 yr	No serious adverse events reported	90% were cured and 10% significantly improved after 1 yr; 89% were cured and 11% improved after 2 yr	Mitterberger et al[38]
6	MDSCs	123 patients with SUI	Ultrasonography-guided transurethral injections	1 yr	No serious adverse events reported	79% were completely continent; 13% with substantial and 8% with slight improvement; 4 patients were lost to follow-up after 1 yr	Mitterberger et al[39]

ADMSCs: Adipose-derived mesenchymal stem cells; MDSCs: Muscle-derived stem cells; SUI: Stress urinary incontinence.