Table 4a.
Xenogeneic MSC therapy in AKI I/R preclinical studies.
| Model | Animal/Strain | Treatment | Dose | Adm.route | Outcome | References |
|---|---|---|---|---|---|---|
| AKI I/R | Rat SD |
hASCs | 2 × 106 in 500 μl EBM-2/1% BSA | IA (abdominal aorta) | ↓SCr, tubular damage ↓T cell infiltration in kidneys ↑Tregs |
(150) |
| AKI I/R | Rat Wistar |
hUC-MSCs hASCs |
1 x 106cells in 2 mL saline | IP | UC-MSCs more prominent renal function protection compared to ASCs treated. Amelioration of long-term renal function. ↓β-galactosidase and ↑ Klotho compared to ASCs |
(151) |
| AKI I/R | Rat SD |
hSVF hASCs |
2 x 106cells in 100 μl PBS | IR | ↑Cell proliferation ↓Apoptosis, IL-10, TNF-α |
(152) |
| AKI I/R | Mouse C57BL/6 |
hASCs | IV (tail vein) | ↑ Proliferation, tubular sox9 by release of exosomes ↓TGF-β1 |
(153) | |
| AKI I/R | Rat Wistar |
VEGF-hAFSCs | 1 x 106cells or 5 x 105cells | IA (aorta) | Treatment with higher dose: ↑ SCr, BUN, Acute tubular necrosis, hyaline cast formation. Treatment with lower dose: ↑ Proliferation, FOXP3+ cells. |
(154) |
| AKI I/R | Rat Wistar |
hUCB-MSC | 1 x 106cells | IV (tail vein) | ↓ SCr, BUN, oxidative stress. | (155) |
| AKI I/R | Mouse SCID |
h Gl-MSC hGl-MSC-EVs Progenitor cells from cortical tissue T-CD133+ cells T-CD133+ cells EVs |
1 x 105cells 400–480 x 106Evs |
IV (tail vein) | hGl-MS-EVs: more efficiently improved renal function compared to T-CD133+ EVs. hGl-MSCs: ↑ proliferation of tubular cells. RNAse treated EVs: ineffective |
(156) |
| AKI I/R | Mouse C57 BL/6 |
hERCs | 1 x 106cells | IV (tail vein) | ↓ SCr, BUN, TNF-α, IL-6, IFNγ, splenic and renal CD4+, CD8+ T cells. ↑CD4+, CD25+ Tregs and M2 macrophages |
(157) |
| AKI I/R | Mouse FVB |
Micro RNA-486-5p from hECFCs-derived exosomes | 20 μg | IV (yugular vein) | ↓SCr, BUN ↓Apoptosis ↓Neutrophil infiltration |
(158) |
| AKI I/R | Rat | hWJ-MSC-EVs | 100 μg EVs | IV (cava caudalis) | ↓Apoptosis, sNgal ↑Nrf2/ARE, HO-1 |
(159) |
| AKI I/R | Rat | hUC-MSC | 100 μg | IV (caudal vein) | ↓Apoptosis ↑VEGF ↓HIF-1α |
(160) |
| AKI I/R | Rat Sprague-Dawley |
hWJ-MSC-EVs | 100 μg | IV (caudal vein) | ↓Cell apoptosis ↓Expression of miRNA-30 |
(161) |
| AKI I/R | Mouse NOD.CB1-Prkdc scid/J |
hUC-MSC and hUC-MSC-EVs | 1 x 106in 100 μl PBS | IV (yugular vein) | ↓ SCr, tubular necrosis, oxidative stress, apoptosis. No cell persistence in kidneys. |
(30) |
| AKI I/R | Rat SD |
hUC-MSC-MVs | 30 μg | IV (cava caudalis) | ↓Collagen deposition, proliferation tubular cells. ↑HGF mRNA expression. TGF-β1, IGF-1 and EGF not affected. mRNAse treatment abolishes renoprotective effect |
(162) |
| AKI I/R | Mouse C57BL/6 |
hWJ-EPCs | 5 x 105cells | IR (subcapsular space) | Cells found in cortex at 1–2 days post AKI and in medulla and cortex 7 days post AKI. ↓ SCr, tubular necrosis and dilation ↑Microvascular density |
(163) |
| AKI I/R | Rat Wistar |
hAFSCs with renal progenitor phenotype | 1 x 106 cells in 800 μl fresh expansion media | IA (intra aorta, directed to kidney by subsequent clamping) | ↓ SCr, tubular necrosis, cast formation, macrophage infiltration, myofibroblast formation, interstitial fibrosis | (164) |
| AKI I/R | Mouse NOD.CB1-Prkdc scid/J |
hiPSCs | 1.5 x 106cells | IR (subcapsular) | ↓ SCr, BUN, tubular necrosis, interstitial fibrosis | (165) |
| AKI I/R | Mouse C57BL/6 |
hSHEDs | 1 x 106cells in 10μl PBS | IR (subrenal capsule) | ↓ SCr, BUN, infiltration of macrophages and neutrophils, MIP-2, IL-1β, MCP1 | (166) |
| AKI I/R | Rat SD |
hASCs hypoxia preconditioned | 2 x 106cellsin 100μl saline | IR (renal cortex) | ↓ SCr, BUN, apoptosis, histological injury. ↑Vascularization In hypoxia preconditioned compared to non-hypoxia preconditioned |
(78) |
| AKI I/R | Mouse C57BL/6 |
hBM-MSC | 1 x 106 | IV | Homing to kidneys ↓SCr, BUN, KIM-1 M2 macrophage polarization |
(167) |
| AKI I/R | Rat SD |
hWJ-MSC-MVs | 100 μg MVs | IV (cava caudalis) | ↓Tubular necrosis, apoptosis, CD68+ macrophages, CX3CL1, α-SMA. ↑Cell proliferation, IL-10 |
(168) |
| AKI I/R | Mouse C57BL/6 |
hUCB-MSC | 1 x 106 before AKI | IP | ↓IFN⋎ ↑VEGF ↑%Tregs |
(169) |
| AKI I/R | Rat SD |
hWJ-MSC | 2 x 106 in 500 μl serum-free medium | IV | Shifting HGF/TGF-β1 to HGF Reduction in overall kidney fibrosis |
(170) |
| AKI I/R | Mouse C57BL/6 |
hUC-MSC | 2 x 106 24 h after AKI | IV (caudal vein) | ↓Apoptosis ↑M2 macrophages |
(171) |
| AKI I/R | Rat SD |
hUCB-MSC- EVs | EVs only EVs+IFN⋎ |
IA (carotid artery) | EVs only ↓serum creatinine, urea, cute tubular necrosis. EVs+ IFNγ No ameliorative effect |
(172) |
| AKI I/R | Mouse NOD.CB1-Prkdc scid/J and FVB/NJ |
hUCB-MSC CD133+ | 1 x 106cells in 100 μl saline | IV (jugular vein) | ↑ SCr and urea, k+ and PO4, tubular injury | (173) |
| AKI I/R | Rat Wistar |
EPC-MVs | 30 μg | IV | ↑Tubular cell proliferation ↓Apoptosis, leukocyte infiltration, interstitial fibrosis. Loss or renoprotective effect when treated with RNAse, Dicer knock-down or depletion of miRNA-126 and miRNA-296 |
(174) |
| AKI I/R | Rat SD |
hBM-MSC- MVs | 30 μg | IV | ↓ SCr, BUN in acute phase, apoptosis, kidney fibrosis. Treatment with RNAse abolish renoprotective effects |
(175) |
| AKI I/R | Rat Wild type |
hMSCs from fetal membranes | 1 x 106 in 150 μl PBS MSCs only or pre-treated with butyric acid |
IR | ↓ SCr, urea, IFNγ, IL-1β, IL-1α, IL-6. ↑VEGF |
(176) |
| AKI I/R | Rat | Hepatocyte growth factor modified hUC-MSCs | Not specified | IA (carotid artery) | ↓SCr, BUN ↓Hyperemia, tubular cast formation ↓Caspase-3 ↑Tubular cell proliferation |
(177) |
| AKI I/R | Rat SD |
hUCB-MSC | 1 x 106in 500 μl saline | IA (carotid artery) | No transdifferentiation into renal cells. ↓SCr, urea, caspase-3, IL-1β |
(178) |