Chinese Journal of Tissue Engineering Research ›› 2019, Vol. 23 ›› Issue (29): 4629-4636.doi: 10.3969/j.issn.2095-4344.1799

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Astragaloside-incubated adipose-derived stem cells for the treatment of diabetic nephropathy

Gao Junli1, 2, Zhu Yunjie1, Liu Guoxiang1, Wang Weiwei1, Zhang Jinyuan1   

  1. 1Department of Nephrology, the 455th Hospital of PLA, Shanghai 201203, China; 2Department of Nephrology, Jinshan Branch, Shanghai Sixth People’s Hospital, Shanghai 201500, China
  • Revised:2019-03-20 Online:2019-10-18 Published:2019-10-18
  • Contact: Wang Weiwei, MD, Associate chief physician, Department of Nephrology, the 455th Hospital of PLA, Shanghai 201203, China
  • About author:Gao Junli, Master, Department of Nephrology, the 455th Hospital of PLA, Shanghai 201203, China; Department of Nephrology, Jinshan Branch, Shanghai Sixth People’s Hospital, Shanghai 201500, China
  • Supported by:

    Shanghai Advanced Chinese and Western Medicine Talents Training Program, No. ZY3-RCPY-4-2039 (to WWW); Medical Science and Technology Innovation Project of the Nanjing Military Region, No. 14ZX05 (to WWW)

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Abstract:

BACKGROUND: Proteinuria is an independent risk factor for the progression of diabetic nephropathy, and the occurrence and development of proteinuria is closely related to podocyte injury.
OBJECTIVE: To observe the effect of astragaloside-incubated human adipose-derived stem cells (Ast-hADSCs) on renal injury in a rat model of diabetic nephropathy.
METHODS: Human adipose-derived stem cells were purchased from ATCC, USA. Male Sprague-Dawley rats were purchased from the Animal Experimental Center of Shanghai University of Traditional Chinese Medicine. The study protocol was approved by the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine. Rats were randomly divided into normal group, model group, hADSCs group and Ast-hADSC group. Animal models of diabetic nephropathy were established by left kidney extraction combined with streptozotocin injection in the latter three groups. hADSCs or Ast-hADSCs suspension was infused via the tail vein in the two intervention groups, every 2 weeks, for six sessions. Rats in the model group were given the same volume of normal saline. Levels of renal function indicators, blood lipids, urine microalbumin and urine protein were detected at 23 weeks. The pathological changes and glomerular area of the kidney were observed by hematoxylin-eosin staining and Masson staining. The podocyte density was detected by WT-1 staining. The distribution of stem cells in the kidney was observed by laser confocal microscopy.
RESULTS AND CONCLUSION: Compared with the model group, there was a reduction in total cholesterol, urine microalbumin and urine protein levels decreased in the two intervention groups. Moreover, a greater reduction was found in the Ast-hADSC group than the hADSC group (P < 0.05). Triacylglycerol, low-density lipoprotein, urea nitrogen, high-density lipoprotein levels were similar in the model, hADSC and Ast-hADSC groups (P > 0.05). Renal pathological findings revealed a relief in renal damage and reduced renal index and glomerular cross-sectional area but significantly increased podocyte density in the hADSC and Ast-hADSC groups (P < 0.01). The renal pathological changes of the Ast-hADSC group were superior to those of the hADSC group (P < 0.05). Under the laser confocal microscope, a small amount of red fluorescence was expressed in the kidney. These results indicate that transplantation of human adipose-derived stem cells through the tail vein can increase the density of podocytes, reduce renal damage, and improve proteinuria in diabetic nephropathy rats. Incubation with astragaloside IV for 48 hours can promote the efficacy of human adipose-derived stem cells in the repair of damaged kidney tissue in diabetic nephropathy rats.

Key words: diabetic nephropathy, human adipose-derived stem cells, astragaloside IV, PKH26, cell transplantation, podocytes, proteinuria, renal function

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