Table 1.
MSCs as treatment for DN
| Source of MSCs | Experimental model | Route of injection | In vivo localization of MSCs | Mechanism of action | Findings |
|---|---|---|---|---|---|
| AD-MSCs | SD rats + STZ n = 8/group |
Intravenous | Kidney | Effect on MAPK signaling pathway, suppression of oxidative stress and inflammatory response. | AD-MSCs treatment reduced oxidative damage and expression of pro-inflammatory cytokines, p-p38, p-ERK and p-JNK [75] |
| BM-MSCs | Wistar rats + STZ n = 16/group |
Intravenous | Kidney | Suppression of inflammatory response and inhibition of MCP-1 expression by secreting HGF. | AD-MSCs treatment reduced hyperglycemia and albuminuria, decreased the expression of fibronectin, Collagen I, MCP-1 and pro-inflammatory cytokines while the expression of HGF was up-regulated [77] |
| NOD/scid mice + STZ n = 9/group |
Intracardiac | Pancreas and kidney | Increased insulin secretion and improved renal lesions. | Successful homing of human BM-MSCs in the kidney of diabetic mice resulted in improvement of mesangial thickening and macrophage infiltration [76] | |
| SD rats + STZ n = 16/group |
Intracardiac | Heart, Pancreas and kidney | Decreased blood glucose | BM-MSCs treatment ameliorated DN characterized by decreased blood glucose, albumin/creatinine ratio and renal hypertrophy [78] | |
| C57BL/6 mice + STZ n = 8/group |
Intravenous | Pancreas and kidney | β-pancreatic islets regeneration | BM-MSCs treatment resulted in regeneration of pancreatic islets and prevented kidney damage [3] | |
| C57BL/6 mice + STZ n = 20/group |
Intravenous | Kidney and bone marrow | Produced renotrophic factors or anti-inflammatory cytokines | MSC treated mice maintained basal levels of albuminuria and only showed slight tubular dilatation [79] | |
| Wistar rats + STZ n = 12/group |
Intravenous | Kidney | Inhibited oxidative stress and reduced cellular glucose uptake mediated by GLUT1 | BM-MSCs treatment reduced hyperglycemia, albuminuria and renal mass index. Glomerulosclerosis, expression of collagen I and fibronectin was significantly reduced. Oxidative stress was also markedly reduced. The expression of TGF-β and membrane localization of GLUT1 was also down-regulated by MSCs [80] | |
| Albino rats + STZ n = 20/group |
Intravenous | Kidney | Paracrine action via different growth factors such as VEGF, TGFβ & TNFα and antiapoptotic action via bcl2 & Bax genes | BM-MSCs treatment decreased albuminuria, normalized serum urea and creatinine levels, increased VEGF, and bcl2 while decreasing TNF-α, fibrogenic growth factor TGF β, and Bax [95] | |
| UC-MSCs | NRK-52E SD rats + STZ n = 7/group |
Intravenous | Kidney | Secretion of humoral factors | UC-MSCs treatment prevented DN. However, renal hypertrophy was observed. There was no effect on blood glucose level [90]. |