Effects of conditioned media derived from human Wharton’s jelly mesenchymal stem cells on diabetic nephropathy and hepatopathy via modulating TGF-β and apelin signaling pathways in male rats

Figures

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  Fig. 1. The flow cytometry revealed the frequency of hWJ-MSCs that reacted to CD90 and CD73 was high, whereas the frequency of the cells that responded to CD34 and CD144 was negligible (A), Oil red O staining showed that the cells stored lipid droplets in the presence of adipogenic medium (B), and Alizarin red S showed that the cells deposited Ca2+ in the presence of osteogenic medium (C)

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  Fig. 2. Timeline and protocol of conditioned media therapy as well as the identification of rat DM model. The timeline of rat treatment from day 0 to week 11 (A) and FBG concentration curve on three consecutive days after STZ injection (B). Data are expressed as mean ± SEM (n = 10). ****P < 0.0001, ***P < 0.001, and **P < 0.01 represent significant differences with controls. DM = Diabetic mellitus; hWJ-MSCs-CM = Conditioned media derived from human Wharton’s jelly mesenchymal stem cells; FBG = Fasting blood glucose; STZ = Streptozotocin

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  Fig. 3. The effects of three weeks of hWJ-MSCs-CM treatment (500 µL per rat, i.p.) on serum creatinine (A), V0 (B), and GFR (C) in rats with DM. Data are expressed as mean ± SEM (n = 10). ****P < 0.0001 represents significant differences between experimental groups. DM = Diabetic mellitus; hWJ-MSCs-CM = Conditioned media derived from human Wharton’s jelly mesenchymal stem cells; V0 = urine flow rate; GFR = glomerular filtration rate

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  Fig. 4. The effects of three weeks of hWJ-MSCs-CM treatment (500 µL per rat, i.p.) on serum activity of AST (A), ALT (B), ALP (C), LDH (D) enzymes, and total bilirubin (E) in rats with DM. Data are expressed as mean ± SEM (n = 10). *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001 represent significant differences between experimental groups. DM = Diabetic Mellitus; hWJ-MSCs-CM = Conditioned media derived from human Wharton’s jelly mesenchymal stem cells; AST = aspartate aminotransferase; ALT = alanine aminotransferase; ALP = alkaline phosphatase; LDH = lactate dehydrogenase

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  Fig. 5. The effects of three weeks of hWJ-MSCs-CM treatment (500 µL per rat, i.p.) on gene expressions of apelin and TGF-β in the kidney (A and B) and liver (C and D) in rats with DM. Data are expressed as mean ± SEM (n = 7). *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001 represent significant differences between experimental groups. DM = Diabetic Mellitus; hWJ-MSCs-CM = Conditioned media derived from human Wharton’s jelly mesenchymal stem cells; TGF-β = transforming growth factor-beta

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  Fig. 6. Hematoxylin and Eosin (H & E) staining of pancreas tissue; photomicrographs of the control, diabetic (without treatment), and diabetic rats treated with condition media (CM) of human umbilical cord Wharton’s jelly mesenchymal stem cells (hWJ-MSCs), [×200 and ×400 magnifications; Scale bar: 50 μm]. Microscopic views of the pancreas of control rats (A and B); diabetic rats with severe necrotic changes in the islets (black circle) and severe atrophy of the acinar parts (C and D); diabetic rats treated with condition media without any specific pathological changes except a mild decrease in the islet cells number and diameter (E and F)

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  Fig. 7. Hematoxylin and Eosin (H&E) staining of kidney tissue; photomicrographs of the control, diabetic (without treatment), and diabetic rats treated with condition media (CM) of human umbilical cord Wharton’s jelly mesenchymal stem cells (hWJ-MSCs), [×400 magnifications; Scale bar: 50 μm]. Microscopic views of the kidney of control rats (A); diabetic rats with marked dilatation of the urinary space (blue arrow), interstitial hemorrhage (white arrow), and mononuclear infiltration (green arrow) (B); diabetic rats treated with condition media without any specific pathological changes except partial hyperemia and slight swelling of tubular cells (C)

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  Fig. 8. Hematoxylin and Eosin (H&E) staining of liver tissue; photomicrographs of the control, diabetic (without treatment), and diabetic rats treated with condition media (CM) of human umbilical cord Wharton’s jelly mesenchymal stem cells (hWJ-MSCs), [×200 and ×400 magnifications; Scale bar: 50 μm]. Microscopic views of the liver of control rats (A and B); section from the liver of the diabetic group with degenerated hepatocytes, karyolysed nuclei, extensive necrosis (C), mild fibrosis, bile duct proliferation (C, arrow), and lymphatic cell infiltration in parenchymal areas (D, two head-arrows); diabetic rats treated with condition media without any specific pathological changes except a mild degeneration and locally inflammatory cell infiltration (E and F)