Table 4b.
Xenogeneic MSC therapy in Cisplatin-induced AKI preclinical studies.
| Model | Animal/Strain | Treatment | Dose | Adm. route | Outcome | References |
|---|---|---|---|---|---|---|
| Cisplatin-induced AKI | Rat NIH-Foxn1rn |
hKDCs | 106 cells in 500 μl PBS (twice) | IV (tail vein) |
↓FITC-sinistrin t1/2, sCr, serum urea, urinary albumin, tubular luminal area | (86) |
| Cisplatin-induced AKI | Mouse C57BL/6 |
hUCB-MSC | 106 cells. Early and late treatment |
IV (tail vein), IP |
Time-sensitive effect of MSCs. hUCB-MSCs early treatment: ↓BUN, apoptosis, tubular injury scores. ↑Treg. ↑anti-inflammatory and ↓pro-inflammatory cytokines Renoprotective effect addressed to immunomodulation activity. |
(31) |
| Cisplatin-induced AKI | Mouse BALB/cOlaHsd |
hUC-MSC+ATG pre-treatment |
5 x 105 cells |
IV | ↓BUN, sCr, kidney weight, in situ inflammation and oxidative stress | (179) |
| Cisplatin-induced AKI | Rat SD |
hASCs | 5 x 106 cells | IV (tail vein) |
↓BUN, sCr, oxidative stress, histological indices of injury in the renal cortex and outer medulla. | (180) |
| Cisplatin-induced AKI | Rat SD |
hASCs, hAFSCs | 5 x 106 cells | IV (tail vein) |
↓BUN, sCr, oxidative stress. ↑Regeneration and proliferation achieved with hAFSCs compared to hASCs. |
(181) |
| Cisplatin-induced AKI | Rat SD |
hAFSCs | 5 x 106 cells | IV (tail vein) |
↓BUN, sCr, oxidative stress, fibrosis. ↑Tissue regeneration. Renoprotective effect addressed to paracrine antioxidant activity. |
(182) |
| Cisplatin-induced AKI | Mouse BALB/c nude |
HIF-1α-hASCs | 105 cells per 200 μl | IV (tail vein) |
↓BUN, sCr, TNF-α, tubular damage score. ↑Antiapoptotic activity, HO-1 gene expression |
(183) |
| Cisplatin-induced AKI | Rat SD |
hASCs | 1–2 x 106 cells in 1 ml saline | IV (tail vein) |
↓BUN, sCr, apoptosis ↑Tubular cell proliferation |
(184) |
| Cisplatin-induced AKI | Mouse NOD-SCID |
RPC-hiPSCs | 5 x 105 cells |
IV (tail vein) |
↓ BUN, renal tubular damage. | (88) |
| Cisplatin-induced AKI | Mouse C3H |
hBM-MSC + pFUS pre-treatment | 106 cells |
IV (tail vein) |
↓BUN, sCr, mouse TNF-α, apoptosis, necrosis. ↑Human IL-10, mouse VEGF. M1 to M2 macrophage phenotype shift. pFUS improves MSCs homing to injured kidneys and increases the aforementioned outcome. |
(185) |
| Cisplatin-induced AKI | Rat SD |
hASCs, hAFSCs | 5 x 106 cells | IV (tail vein) |
↓sCr, tissue oxidative stress. ↑Tissue regeneration and proliferation. Renoprotective effect achieved by both cell types. An antioxidant activity is proposed. |
(186) |
| Cisplatin-induced AKI | Rat White albino |
hUCB-HSCs | 3 x 106 cells | IP | ↓BUN, sCr, TNF-α, HGF, IGF-1, VEGF, p53. | (187) |
| Cisplatin-induced AKI | Rat SD |
hUC-MSC | 2 x 106 Cells in 500 μl saline solution |
IV (tail vein) |
↓BUN, sCr, apoptosis, IL-1b, and TNF-α, inflammatory cell accumulation, kidney interstitial fibrosis. ↑Renal cell proliferation. Homing to the renal lesion site observed. EMT inhibition. |
(32) |
| Cisplatin-induced AKI | Mouse BALB/c nude | hUSSC | 105 cells in 500 μl PBS | IV (tail vein) |
No amelioration observed. No statistically significant changes in the levels of BUN, sCr, TGF-β 1, HGF, and IGF-1. Cell transplantation worsens the kidney architecture (↑ injury score) |
(188) |
| Cisplatin-induced AKI | Rat SD |
hUC-MSC-Exs, hUC-MSC- CM |
Exs: 200 μg. CM: not specified |
Renal capsule injection (both kidneys) | Exs: ↓Oxidative stress, tubuli apoptosis. ↑ Cell proliferation. No significant changes in the levels of BUN and sCr observed. CM: No notable changes observed. |
(189) |
| Cisplatin-induced AKI | Mouse C57BL6/J | hESC-MPs | 5 x 105 cells |
IV (tail vein) |
BUN, sCr, apoptosis, pro-inflammatory cytokines. ↑Anti-inflammatory cytokines, tubular cell proliferation. Cells engraftment in the kidney. |
(190) |
| Cisplatin-induced AKI | Rat SD |
hADSC, hASC-CM |
hASCs: 5 x 105 cells, hASC-CM: 4 ml |
hASCs: IV (tail vein), hASC-CM: IP |
hASCs and CM: ↓BUN, sCr, renal tissue injury, tubular apoptosis, TNF-α, NF-kB, COX2. ↑Animal survival. However, additional studies are needed to clarify if the protective effects of CM are equivalent to Ad-MSC treatment. |
(79) |
| Cisplatin-induced AKI | Rat SAS- SD |
hBM-MSC-CM | 1 ml | IV (penile vein) |
↓BUN, sCr, renal tissue injury, tubular apoptosis, IL-1β, TNFα, IL-6 and IL-1ra. ↑IL-10, animal survival |
(191) |
| Cisplatin-induced AKI | Mouse NOD-SCID |
hAFSCs | 5 x 105 cells |
IV | ↓BUN, sCr, renal tissue injury, apoptosis. ↑Animal survival. Cells engraftment in the peritubular region. Preconditioning with GDNF enhances the regenerative potential of hAFSCs. |
(192) |
| Cisplatin-induced AKI | Mouse SCID | hBM-MSC-MVs | Single dose: 10 μg. Multiple dose: 100 μg + 5 x 50 μg |
IV (tail vein) |
MVs single dose: ↓BUN, sCr. ↓↓Apoptosis. ↑Survival. MVs multiple doses: ↓↓BUN, sCr. ↓Apoptosis. ↑↑Survival. Kidney morphology restoration. |
(56) |
| Cisplatin-induced AKI | Mouse BALB/c |
hE-MSC, VEGF-hE-MSCs |
5 x 105 cells per 500 μl | IV (tail vein) |
VEGF-hE-MSC can strengthen the renoprotective effect of MSCs by antiapoptotic effect and proliferation on peritubular capillaries. | (193) |
| Cisplatin-induced AKI | Mouse BALB/c |
hUSSC-CM | No amelioration in terms of serum urea and creatinine, histopathologic examinations and physical activity score was found. | (194) | ||
| Cisplatin-induced AKI | Mouse NOD-SCID |
hUCB-MSC | 5 x 105 cells |
IV | ↓BUN, renal tubular damage, oxidative stress, apoptosis, inflammation. ↑Animal survival, tubular cell proliferation, serum HGF, kidney mRNA HGF |
(85) |
| Cisplatin-induced AKI | Mouse NOD-SCID |
hBM-MSC | 5 x 106 cells |
IP | ↓BUN, amylase, phosphorous, alanine aminotransferase, creatinine, cytokines/chemokines (MIP-2, G-CSF, KC, IL, MCP-1, PDGF, TNF-α, GM-CSF, IL-6). ↑Animal survival. |
(195) |
| Cisplatin-induced AKI | Mouse NOD-SCID |
hBM-MSC | 5 x 105 cells(500 μl) | IV (tail vein) |
↓BUN, sCr, renal tissue injury, tubular cell apoptosis, peritubular capillary changes. ↑Animal survival. |
(196) |