Application prospects of urine-derived stem cells in neurological and musculoskeletal diseases

Table 1 Surface markers of urine-derived stem cells

Surface markers in USCs		Ref.
MSC-like markers	CD73, CD90, CD29, CD44, CD146
	CD73, CD29, CD44
	CD73, CD90, CD44, CD146
	CD73, CD90, CD105 (high), CD44, CD146
	CD73, CD90, CD146
	CD73, CD90, CD105, CD29, CD24, CD146
	CD73, CD90, CD29
	CD73, CD90, CD29, CD44, CD54, CD166, CD146
	CD73, CD90, CD105, CD29, CD44
	CD90, CD29, CD44
	CD73, CD90, CD105, CD29, CD44, CD166, STRO-1, CD54, CD146
	CD73, CD90, CD105, CD44
	CD73, CD90, CD105, STRO-1 (low), CD146
	CD73, CD90, CD105, CD24, CD29, CD44, CD117, STRO-1, CD146
	CD29, CD44, CD73, CD90, CD105 (low)
	CD24, CD29, CD34, CD44, CD73, CD90
Other pluripotency markers	TRA-1-60, TRA-1-81, SSEA-4, SOX2, OCT4, MYC, KLF4
	SSEA-4
	OCT4, MYC
	OCT4, NANOG	[20]
	CD133
Urinary system markers	Nephrin, WT1	[20]
	PAX2, PAX8
	Uroplakin Ia, cytokeratin 7, cytokeratin 19
MP markers	PAX7, MYF5, MOYD, desmin, dystrophin, myogenin, α-smooth muscle actin	[24]

CD: Cluster of differentiation; KLF: Kruppel-like factor 4; MP: Myogenic pedigree; MSC: Mesenchymal stem cells; MYC: Myelocytomatosis oncogene; MYF: Myogenic factor 5; NANOG: Nanog homeobox; OCT4: Octamer binding transcription factor 4; PAX: Paired-box; SOX2: Sex determining region Y-box 2; SSEA-4: Stage-specific embryonic antigen-4; STRO-1: Stromal cell antigen-1; TRA: Tumor resistance antigen; USCs: Urine-derived stem cells; WT: Wilms’ tumor.

Table 2 Reprogramming methods of urine-derived stem cells

Reprogramming method	Vectors	Factors	Ref.
SeV	SeV	OSKM	[15,43,44,48,49,58,60,63,71]
		OCT4, SOX2, NANOG, LIN28
		JDP2, JHDM1B, MKK6, GLIS1, NANOG, ESSRB, SALL4
Exogenous plasmids	Epi	KLD4, MYC, OCT4, SOX2, LIN28, shP53
		OCT4, SOX2, KLF4, miR-302-367
		OCT4, SOX2, NANOG, LIN28, KLF4 and MYC	[85,86]
		OCT4, SOX2, SV40 LT, KLF4 and miR302-367
		OCT4, SOX2, NANOG, MYC, KLF4, LIN28
		OCT4, SOX2, KLF4, and miR-302-367
	pCXLE-hOCT4-shP53-F, pCXLE-hSK, pCXLE-h UL	OSKM, shP53, LIN28
	TET-ON-induced expression vector	OSKM
	pEP4EO2SET2K	OCT4, SOX2, SV40 LT and KLF4, miR-302b, c, a, d and miR-367
SM		Cyclic pifithrin-a, A-83-01, CHIR99021, thiazovivin, NaB, PD0325901
mRNA		OSKM LNg
srRNA		OSKM, NSP 1-4
Lentivirus	Lentiviral vectors	OSKM

ESSRB: Estrogen related receptor beta; Epi: Episomal vector; JHDM1B: Jumonji C domain-containing histone demethylase 1B; KLD4: Kelch domain-containing protein 4miR: MicroRNA; MKK6: Mitogen-activated protein kinase kinase 6; NaB: Sodium butyrate; NSP: Non-structural proteins; OSKM: Octamer-binding transcription factor 4, sex determining region Y-box transcription factor 2, kruppel-like factor 4, and myelocytomatosis oncogene; SeV: Sendai virus; shP53: P53 short-hairpin RNA; SM: Small molecules; srRNA: Self-replicating mRNA; SV40 LT: Simian virus 40 large T antigen.

Table 3 Differentiation and application of urine-derived stem cells and urine-derived pluripotent stem cells

Cells	Differentiation	Factors	Diseases/animal model	Ref.
USCs	NPCs	hEGF, bFGF		[28]
	Neural lineage cells (astrocytes)	Transplantation	CCI model (rat)	[28]
	Neurons	Laminin, PDGF-BB
		VPA, CHIR99021, repsox, forskolin, SP600625, GO6983, Y27632
	NSCs	Cocktail (P, F, V, N) and srRNA (with OSKG)
	Osteoblasts	Silver nanoparticles	Bone defect model
		Y-27632
		Calcium silicate ionic, BMP2
		BMP2, FAK
		BCP-CS
		Surface mineralized BCP		[19]
		BMP2-CSM/Col I hydrogel
	Chondrocytes	Hyaluronic acid with USCs
		Y-27632
		ACM scaffolds
	Muscle cells	VEGF, IGF-1, FGF-1, PDGF-BB, HGF, NGF
		HD myogenic differentiation medium		[103]
		Lentiviral with MYOD
		hp-HA (IGF-1, HGF, PDGF-BB)
	Hepatocytes	Co-culture with HPCs		[5]
UiPSCs	Cardiac myocytes	Activin A, bFGF, BMP4, DKK1, VEGF		[56]
		Cardiomyocyte differentiation kit (Gibco, catA2921201)
		CHIR99021, BIO, KY02111, IWP2
		GIWI2
		HIR99021, IWP2	MI (rat)
	KPCs		AKI	[69]
	Kidney organoids	Y-27632, APEL-2, CHIR99021, hFGF9, heparin
	Neurons, astrocytes	Transplantation	SCI model (rat)
	NPCs	N2B27, dorsomorphin, SB4315242
	HPCs	Flavonoid
	Muscle cells	CHIR99021		[52]
	Neurons, astrocytes, VECs		Simulate the brain microenvironment of diabetes mellitus
	RCs, CCs	RDM
	LB	BMP, BMP4, BMP7, bFGF, WNT3A
	AECs II
	Hepatocytes

ACM: Acellular cartilage extracellular matrix; AECs II: Alveolar type II epithelial cells; AKI: Acute kidney injury; BCP-CS: Biphasic calcium phosphate bioceramic ornamented with chitosan sponge; bFGF: Basic fibroblast growth factor; BIO: 6-bromoindole-3-oxime; BMP: Bone morphogenetic protein; BMP2-CSM/Col I hydrogel: BMP2-releasing chitosan microspheres/type I collagen hydrogel; CCs: Cone cells; CCI: Cerebral cortex injury; Cocktail (P): Puromorphamine; DKK1: Dickkopf WNT signaling pathway inhibitor 1; F: Folliculin; FAK: Focal adhesion kinase; FGF-1: Fibroblast growth factor; GIWI2: Albumin-free GIWI; hEGF: Human epidermal growth factor; HFGF9: Human fibroblast growth factor; HGF: Hepatocyte growth factor; hp-HA: Heparin hyaluronic-acid hydrogel; HPCs: Hematopoietic progenitor cells; IGF-1: Insulin-like growth factor-1; IWP2: Inhibitor WNT protein 2; KPCs: Kidney progenitor cells; LB: Lentoid body; MI: Myocardial infarction model; MYOD: Myogenic differentiation 1; N: Sodium butyrate; NGF: Nerve growth factor; NPCs: Neural progenitor cells; NSCs: Neural stem cells; OSKG: Octamer-binding transcription factor 4, sex determining region Y-box transcription factor 2, kruppel-like factor 4, and GLIS1; PDGF-BB: Platelet-derived growth factor BB; RCs: Rod cells; RDM: Retinal differentiation medium; SCI: Spinal cord injury model; srRNA: Self-replicating mRNA; UiPSCs: Urine-derived pluripotent stem cells; USCs: Urine-derived stem cells; V: Vitamin C; VECs: Vascular endothelial cells; VEE: Venezuelan equine encephalitis; VEGF: Vascular endothelial growth factor; VPA: Valproic acid; WNT3A: Wingless/integrated family member 3A.