Urine-derived stem/progenitor cells: A focus on their characterization and potential

Table 1 Summary of human urine-derived stem cell phenotype

Marker	Percentage of expression, %	Ref.
Embryonic stem cell markers
c-Myc	[+]	[23]
SSEA4	[+++]	[24,29]
	[++++]	[12,23,27,28,30,31]
TRA-1-60	[-]	[23]
	[+]	[27]
TRA-1-81	[+]	[23,27,29]
Hematopoietic stem cell markers
CD11b	[-]	[23]
CD14	[-]	[15,23,27,29]
CD19	[-]	[23,29]
CD34	[-]	[12,13,15,18-20,22-24,28,29,32,33]
CD45	[-]	[12,13,18,19,22-24,28,29,31,33]
CD117	[-]	[12,15,19,24,28]
	[++++]	[27]
Mesenchymal stem cell markers
CD24	[+++]	[27]
	[++++]	[20,27,30-32]
CD44	[++++]	[12,13,15,19,20,22-24,28-33]
CD73	[++++]	[12,13,15,19,20,22-24,27-33]
CD90	[+]	[18,27]
	[++]	[12,29]
	[+++]	[19,23,24,28]
	[++++]	[13,15,20,22,28,30-33]
CD105	[-]	[27,31]
	[+]	[22]
	[++]	[12,24,30]
	[+++]	[18,23]
	[++++]	[15,19,20,28,29,32]
CD133	[-]	[12,15,20,22,33]
	[++]	[20]
	[+++]	[27]
	[++++]	[27]
Collagen I	[++++]	[15]
SRTO-1	[-]	[12,23,30]
	[+]	[31]
VIM	[++++]	[15,20,27]
Endothelial/adhesion markers
CD29	[++++]	[13,20,22,23,29-33]
CD31	[-]	[12,19,23,29-32,34]
CD166	[++++]	[18,23]
Immunogen markers
CMH-I	[+]	[28]
	[+++]	[29]
	[++++]	[23]
CMH-II	[-]	[18,22-24,28,29,33]
Kidney markers
AQP1	[++++]	[20]
AQP2	[-]	[20]
	[++]	[20]
CD13	[++++]	[18,23,29]
CD54	[+++]	[18]
	[++++]	[23]
CD224	[++++]	[23]
Pax8	[-]	[23]
NPHS1	[-]	[20]
	[++]	[20]
NR3C2	[++++]	[23]
SLC12A1	[-]	[20]
	[++]	[20]
UMOD	[-]	[20]
	[++]	[20]
Pericyte markers
CD140b	[-]	[19,23]
	[+]	[32]
CD146	[++++]	[12,19,23,29-32]
NG2	[-]	[19,23,32]
Other markers
KRT18	[-]	[20]
	[++]	[20]

[-]: 0-10%; [+]: 10%-30%; [++]: 30%-50%; [+++]: 50%-80%; [++++]: 80%-100% of expression.

Table 2 Summary of urine-derived stem cell differentiation reports

Cell type	Medium	Supplements	Initial density	Protocol duration	Note	Ref.
“MSC-like” differentiated cell types
Adipogenic cells	DMEM	Dexamethasone 1 µmol/L, isobutyl-1 methylxanthine 500 µmol/L, indomethacin 66 µmol/L, hydrocortisone 500 µmol/L	14000 cells/cm²	24 d	2 d in DMEM without supplement before differentiation	[15]
	DMEM low glucose	Dexamethasone 1 µmol/L, isobutyl-1 methylxanthine 500 µmol/L, indomethacin 100 µmol/L, insulin 10 µg/mL	20000 cells/cm²	28 d	/	[30]
	Specific adipogenic medium	FBS (optional)	1000 to 5000 cells/cm²	14 d	/	[13,22,23,33,39]
	Specific adipogenic medium	NA	80% of confluency	14 d	/	[24]
Chondrogenic cells	DMEM/Ham's F12	Fetal calf serum 10%, insulin 6 µg/mL, ascorbic acid 2P 0.2 mmol/L, TGF-b1 10 ng/mL	1500 cells/cm²	28 d	/	[15]
	Specific chondrogenic medium	NA	50000 cells/cm²	28 d	/	[22,24]
	Specific chondrogenic medium	NA	300000 cells to 1000000 cells	28 d	Cell aggregation in conical polypropylene tube before differentiation	[23]
Osteogenic cells	DMEM low glucose	Dexamethasone 10-100 nmol/L, ascorbate2-phosphate 50-1500 µmol/L, glycerophosphate 10 mmol/L, FCS 10%, Vit D3 10 nmol/L (optional)	1500 to 4000 cells/cm²	28 d	/	[15,30]
	DMEM low glucose	FBS + osteogenic supplement	4000 cells/cm²	28 d	/	[23]
	Specific osteogenic medium	NA	1000 cells/ cm²	28 d	/	[39]
	Specific osteogenic medium	NA	80% confluency at P4	14 d to 21 d	/	[22,24,33]
Other cell types
Endothelial cells	EBM-2	VEGF 50 ng/mL + FBS (optional)	3000 to 5000 cells/cm²	9 d to 14 d	Coating with fibronectin + 2 d of preculture	[23,31,32]
	Microbeads	VEGF	1000 cells/cm²	14 d	MD	[35]
Neuronal cells	Specific nerve induction medium	NA	6000 cells/cm²	2 d	Pre-culture with DMEM + 20% FBS + 10 ng/mL bFGF 24 h	[23]
	DMEM F12	hEGF 20 ng/mL, bFGF 40 ng/mL, B27 2%, NEAA 1%, l-glutamine 1%, insulin-transferrin-selenite 1%.	20%-30% of confluency	12 d	Coating: Polystyrene	[22]
	NeuroCult NS-A differentiation kit	NA	100000 cells/cm²	7 d	Preculture	[24]
	NM3 basic neuronal induction medium	Y27632 10 μmol/L, A8301 5 μmol/L, CHIR99021 3 μmol/L, TTNPB 1 μmol/L, forskolin5 μmol/L, valproic acid 0.5 mmol/L, sodium butyrate 0.1 mmol/L	MD	MD	Coating with Matrigel and preculture (2 d)	[37]
Skeletal myogenic cells	DMEM	Skeletal supplement + SVF 10%, Horse serum 5%, hydrocortisone 50 µmol/L, dexamethasone 0,1 µmol/L	MD	28 d	/	[23]
	Conditioned medium	NA	MD	28 d	12 h of culture of medium with skeletal myogenic cells	[23]
	Conditioned medium	NA	80% confluency	14 d	Culture of medium with skeletal myogenic cells	[24]
Smooth muscle cells	DMEM + EFM (1:1)	FBS, TGF-β1 (2.5 ng/mL), PDG-BB (2.5 to 5 ng/mL)	1000 to 2000 cells/cm²	14 d	/	[12,19,23,34,36]
Renal differentiation
Podocytes	VRAD: DMEMF12	FBS 10%, vitamin D3 100 nmol/L, retinoic acid 100 µmol/L	MD	48 h	MD	[14]
Tubular cells	REGM	Hepatocyte growth factor 50 ng/mL	MD	21 d	MD	[14]
Urothelium cells	KFSM + EFM (1:1)	FBS 2%, EGF 30 ng/mL	3000 cell/cm²	14 d	MD	[36]
	KFSM	FBS 2%, EGF 30 ng/mL	3000 cell/cm²	14 d	MD	[34]
	KFSM + EFM (4:1)	FBS 2%, EGF 30 ng/mL	3000 cells/cm²	14 d	/	[36]
	DMEM + KFSM (4:1)	FBS 8%, EGF 30 ng/mL	1,000 cells/cm²	14 d	/	[19]
	Conditioned medium from urothelial cells 8 h + EFM + KFSM (1:1)	EGF 30 ng/mL	50000 cells/cm²	7 to 21 d	Dynamic culture	[21]
	Conditioned medium of smooth muscle cells 12 h + KFSM (1:1)	NA	50000 cells/cm²	7 to 21 d	Dynamic culture	[21]

bFGF: Basic fibroblastic growth factor; DMEM: Dulbecco’s modified Eagle’s medium; EFM: Embryonic fibroblast medium; EGF: Endothelial growth factor; FBS: Fetal bovine serum; FCS: Fetal calf serum; KFSM: Keratinocyte free serum medium; MD: Missing data; MSC: Mesenchymal stem cell; NA: Not applicable; NEAA: Non-essential amino acids; PDG-BB: Platelet-derived growth factor BB; SVF: Stromal vascular fraction; TGF: Transforming growth factor; VEGF: Vascular endothelial growth factor.