Laboratory of Transplant Engineering and Immunology
West China Hospital, Sichuan University
Intravenous injection of human mesenchymal stem cells ameliorated early renal damage in diabetic rhesus monkey model
Xingxing An1, MM Shi1, YJ Yuan1, JP Liu1, YN Chen1, B Chen1, L Li1, GN Liao1, J Zhang1, G Yang1, SY Liu1, RX Luo1, YM Li1, LZ Li1, JQ Cheng1, YR Lu1.
1Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
Background: Mesenchymal stem cells (MSC) have multi-directional differentiation potential, and play an important role in immune modulation. Accumulated evidence shows that MSC are capable to regulate inflammation in the microenvironment of specific tissues and participate in the repair of tissue damage through direct contact and/or paracrine. Diabetic nephropathy is one of the most severe chronic complications of diabetes, and inflammation is the key pathophysiological factor for its development. In previous study, we have successfully established rhesus monkey diabetic models with early renal damage characterized by microalbuminuria. In the present research, we aim to study the effects of intravenous transfusion of human MSC in early diabetic renal damage of rhesus monkeys, which would provide insight for the clinical application of MSC in diabetic nephropathy.
Methods: Three diabetic rhesus monkeys (male, 8 to10 years old, induced by STZ，80 mg / kg, iv) were given high salt and high fat diet to induce early renal damage. Human umbilical cord MSC were intravenously injected at 2 x 106/Kg every 2 weeks for total 4 times. CM-DiI labeled MSC were administrated at the last injection. The animals were monitored for survival, blood and urine biochemistry, kidney imaging by Color Doppler ultrasound and renal histology before and after MSC treatments.
Results: After MSC treatments, the animals showed more stable vital signs than before. One month after the last injection of MSC, improved renal function was observed (Table 1): One of the three recipients has shown robustly reduced urine albumin excretion (UAE) and albumin to creatinine ratio (monkey 1), and other two have shown slighter alterations. All of them showed decreases in the serum levels of LDL, Chol, Urea and UA2. Moreover, HE and Masson staining from the renal biopsies 2 weeks after the last injection showed that the pathological damages in kidney fibrin and glomerulus were alleviated (Fig. 1A). Interestingly, the fluorescent tracing of MSC grafts showed that the MSC specifically accumulated around the renal tubules (Fig. 1B). In addition, real-time PCR and immunohistochemistry analysis indicated that expressions of IL-1, IL-6, IL-8, MCP-1 and TNF-α have been distinctly repressed in renal tissues.
Conclusion: This study suggests that MSC infusion is able to ameliorate pathological damage of kidney and improve renal function in early nephropathy of diabetic monkeys. Our research has provided important preclinical evidence for the therapeutic potential of MSC in the treatment of early-stage diabetic nephropathy.
National Natural Science Foundation of China (No.81370824).
11:00 - 12:30
|Mesenchymal Stromal Cells||Intravenous injection of human mesenchymal stem cells ameliorated early renal damage in diabetic rhesus monkey model||Room 111-112|