Urine-Derived Stem Cells: The Present and the Future

Table 1

Disease-specific iPSCs derived from urine cells.

Disease	Genetic etiology/mutation sites	Reprogramming factors	Reprogramming strategy	Major findings	Refs
Type 2 long QT syndrome	KCNH2/A561P.c7:150 648 800G>C	OSKMLN + SV40LT	Episomal vectors	A561P-UhiPSC lines were established.; A561P-UhiPSCs could be differentiated into functional cardiomyocyte cells.; A561P KCNH2 mutation caused a trafficking defect of the HERG channel.; HERG A561P mutation increased the susceptibility to arrhythmia.	[16]
Multiple endocrine neoplasia type 1 syndrome	Men1/exon 9	OSK + miR-302-367	Episomal plasmids	MEN1-iPSC lines of male and female were established.; No functional experiments were achieved.	[41, 42]
Novel heterozygous PAI-1 mutation	PAI-1/exon 4	OSKM	Sendai virus	PAI-1-iPSC line and the control line were established.; No functional experiments were achieved.	[43, 44]
Hemophilia A	FVIII/intron 22 inversion	OSK + SV40LT	Episomal vectors	HA-iPSC lines were established.; HA-iPSCs could be differentiated into hepatocyte-like cells in vitro.; HA-iPSC-derived hepatocyte-like cells displayed FVIII deficiency.	[45]
Down syndrome	Trisomy 21	OSKM	Episomal vectors	T21-iPSC lines were established.; T21-iPSCs were more sensitive to proteotoxic stress than euploid iPSCs.; T21-iPSCs could be differentiated into glutamatergic neurons and cardiomyocytes.; Neurons fromT21-iPSCs could fire AP similar to euploid iPSCs.	[46]
Spinal cord injury	No verification/no verification	OSKM	Sendai virus	SCI-iPSC lines were established.; SCI-iPSCs could be differentiated into A2B5^+ NPCs.; A2B5^+ NPCs could give rise to neurons and astrocytes after implantation.	[47]
Attention-deficit hyperactivity disorder	No verification/no verification	OSKM	Sendai virus	ADHD-iPSC lines were established.; No functional experiments were achieved.	[48]
Dilated cardiomyopathy	No verification/no verification	OSKM	Sendai virus	DCM-iPSC lines were established.; No functional experiments were achieved.	[49]
Muscular dystrophy	Dystrophin/exon deletion	OSKM	Sendai virus	MD-iPSC lines were established.; MD-iPSCs lack the expression of dystrophin.	[50]
Fibrodysplasia ossificans progressiva	ALK2/R206H	OSKM/OSK + miR-302-367	Sendai virus/episomal vectors	FOP-iPSC lines were established.; Differentiation efficiency into bone-forming progenitors was decreased.; Expression of VEGF receptor 2 in differentiated endothelial cells was reduced.; Mineralization of pericytes from FOP-hiPSCs was increased.	[51, 52]
Systemic lupus erythematosus	No verification/no verification	OSKM	Lentivirus	SLE-iPSC lines were established.; No functional experiments were achieved.	[53]
Cryptorchid	INSL3/c.A178>G, ZNF214/c.A197>G, c.T383>A and c.T754>C, ZNF215/c.T108>A, c.A400>C, c.A780>T, and c.C788>T	OSKM	Lentivirus	Cryp-iPSC lines were established.; Cryp-iPSCs could be differentiated into VASA^+ germ cell.	[54]
Hypercholesterolemia	PCSK9/S127R and R104C/V114A	OSKMLN + SV40LT	Episomal vectors	PCSK9-iPSC lines were established.; PCSK9-iPSCs could be differentiated into hepatocyte-like cells.; PCSK9 secretion and LDL uptake were altered.	[55]
Paroxysmal kinesigenic dyskinesia	PRRT2/c.649dupC	OSKM	Retroviruses	PKD-iPSC lines were established.; PKD-iPSCs could be differentiated into functional glutamatergic, dopaminergic, and motor neurons.; The expression of PRRT2 was decreased in PKD-iPSCs.	[56]

The abbreviations represent a combination of reprogramming factors: O: OCT3/4; S: SOX2; K: KLF4; M: c-MYC; L: LIN28; N: NANOG.