Progress in the application of mesenchymal stem cells to attenuate apoptosis in diabetic kidney disease

Table 1 Role of mesenchymal stem cells on apoptosis in a high glucose cell models and animal models of diabetic kidney disease

Cell types	Animal models/cell	Dose	Injection method	Frequency/time	Outcomes	Ref.
BM-MSCs	STZ-induced SD rats	1 × 106 cells	Tail vein	Once	↑VEGF, Bcl2; ↓TNF-α, TGF-β, Bax	[59]
BM-MSCs	Podocytes	Transfected with miR-124a	Co-culture	24 hours	↓Apoptosis rate, ↓Bax, caspase-3, ↑Bcl2	[79]
BM-MSCs	STZ-induced rats	3 × 106 cells with miR-124a 4 ng/mm3	Tail vein	Once	↓Bax, caspase-3, ↑Bcl2	[79]
BM-MSCs	STZ-induced male C57BL/6 mice	1 × 104 cells	Tail vein	Twice	↓Apoptotic cells, Bax, ROS; ↑ Bcl2	[82]
BM-MSCs	STZ-induced SD rats	2 × 107 cells	Intraperitoneally	One time at 4 weekly intervals	↑ATF3, Bcl2; ↓Fas, FasL, P53, caspase-3, BAX,BAX/BCL -2	[83]
BM-MSCs	High-fat diet and STZ administration	2 × 106 cells	Tail vein		↑LAMP2; ↓β-cell apoptosis	[84]
AD-MSCs	STZ-induced SD rats	1 × 107 cells	Tail vein	Once	↑Bcl2, klotho, ↓Bax, Wnt1, Wnt3a, Snail, β-catenin	[38]
AD-MSCs	STZ-induced SD rats	5 × 106 cells	Tail vein	Five times at 4 weekly intervals	↑WT1, ↓disruption of the tubules and interstitium	[85]
AD-MSCs	MPC5	1 × 105 cells/cm2	Cultured with hAd-MSC-conditioned medium	24, 48, 72 hours	↓Cleaved caspase-3; Maintain the normal arrangement of synaptopodin and nephrin in podocytes	[43]
hUC-MSCs	STZ-induced SD rats	2 × 106 cells	Tail vein	Once a week for 2 weeks	↓Apoptosis rate, ↓Bax, hioredoxin-interacting protein, ↑Bcl2	[89]
hUC-MSCs	STZ-induced SD rats	2 × 106 cells	Tail vein	three times every 10 days	↓TUNEL + cells, ↓caspase-3, ↑Bcl2/ Bax	[90]

TNF: Tumor necrosis factor; BM-MSCs: Bone marrow-derived mesenchymal stem cells; VEGF: Vascular endothelial growth factor; SD: Sprague Dawley; AD-MSCs: Adipose-derived mesenchymal stem cells; hUC-MSCs: Human umbilical cord mesenchymal stem cells; TGF: Transforming growth factor.

Table 2 Role of extracellular vesicles derived from stem cells on apoptosis in a high glucose cell models and animal models of diabetic kidney disease

Exosome source	Animal models	miRNA	Dose	Injection method	Frequency/time	Outcomes	Ref.
BM-MSCs	Renal tubular epithelial cells		5.3 × 107	Co-culture	96 hours	↓TGF-β 1, ↓Apotpsis, ↑ZO-1	[92]
BM-MSCs	HUVECs	miR-146a-5p	100 μL	Co-ulture	48 hours	↑IL-10, ↓apoptosis rate, NF-KB	[93]
AD-MSCs	MPC5	miR-486	25 μg/mL	Co-culture	48 hours	Cleaved caspase-3↓	[94]
AD-MSCs	db/db	miR-486		Tail vein	12 weeks	↓Cleaved caspase-3, ↓p-mTOR	[94]
AD-MSCs	MPC 5	miR-15b-15p	25 μg/mL	Co-culture	24 hours	↑Caspase3, Bcl2, ↓cleaved caspase3	[96]
AD-MSCs	SD rats with type 1 diabetes	MiR-125a	50 μg	Tail vein	Twice a week for 3 weeks	↓Bax, ↑Bcl2, ET1↓	[97]
AD-MSCs	MP5 cells	miR-26a-5p	25 mg/mL	Co-culture	48 hours	↓Cleaved caspase-3, Bax↓ Bcl2↑	[98]
AD-MSCs	db/db mice	miR-26a-5p		Tail vein	Once at 13 weeks	↓TUNEL + cells; ↓cleaved caspase-3, Bax; ↑Bcl2	[98]
HUC-MSCs	Podocytes		30 μg/mL	Co-culture	48 hours	↑Podocytes cell viability, ↓apoptosis of podocytes	[99]
HUC-MSCs	HK2 cells	miR-424-5p	50 μg/mL	Co-culture	48 hours	↓Apoptosis rate, ↓TUNEL + cells, ↓Bax,cleaved caspase-3/caspase-3, ↑Bcl2	[100]
HUC-MSCs	db/db	miR-424-5p	10 mg/kg bw	Tail vein	twice a week for 6 weeks	↓Bax, cleaved caspase-3/total caspase-3, ↑Bcl2	[100]
HUC-MSCs	STZ-induced SD rat	Mi-R-146a-5p	2 × 106	Tail vein	Once a week for 2 weeks	↑IL-10, M2 macrophage marker; ↓IL-1β, IL-6 and TNF-αmRNA, TRAF6, M1 macrophage marker	[101]
HUC-MSCs	Type 2 diabetic BKS. db/db mice	MiR-22-3p	Exo 20, μg/mL	Tail Vein	3 times in the first week, twice a week in the next 3 weeks	↑wnt-1; ↓ Caspase-1, ASC	[102]
HUC-MSCs	Podocytes	MiR-22-3p	20 μg/mL	Co-culture	24 hours	↑Podocytes cell viability; ↓apoptosis of podocytes; ↓Caspase-1	[102]
USCs	STZ-induced SD rat	VEGF, TGF-β1, angiogenin, BMP-7	100 μg	Tail vein	Weekly for 12 weeks	↓Apoptosis rate; ↓TUNEL + cells; ↓caspase-3	[103]
USCs	HPDCs	miR-16-5p	0.4 × 105 cells	Co-culture	4-5 days	↑Podocyte viability; ↓apoptosis rate, Bax, Caspase-3, α-SMA, VEGFA	[104]
USCs	STZ induced SD rat	miR-16-5p	100 μg	Tail vein	once a week for 12 weeks	↓VEGFA, MCP-1, TGF-β1, TNF-α	[104]
USCs	STZ-induced SD rat		2 × 106 cells	Tail vein	Six times every other week	↓TUNEL + cells; ↓caspase-3	[105]

BM-MSCs: Bone marrow-derived mesenchymal stem cells; TGF: Transforming growth factor; HUVECs: Human umbilical vein endothelial cells; AD-MSCs: Adipose-derived mesenchymal stem cells; mTOR: Mammalian target of rapamycin; SD: Sprague Dawley; hUC-MSCs: Human umbilical cord mesenchymal stem cells; USCs: Urothelial stem cells; BMP-7: Bone morphogenetic protein-7; TNF: Tumor necrosis factor.