Feng Zhou1, Yu Hui1, Yongde Xu2, Hongen Lei2, Bicheng Yang2, Ruili Guan2, Zhezhu Gao2, Zhongcheng Xin3, Jianquan Hou4. 1. Department of Urology, First Affiliated Hospital of Soochow University, Soochow University, No. 188, Shizi Street, Gusu District, Suzhou, 215006, China. 2. Molecular Biology Laboratory of Andrology Center, Peking University First Hospital, Peking University, No. A59, Di'anmen West Street, Xicheng District, Beijing, 100034, China. 3. Molecular Biology Laboratory of Andrology Center, Peking University First Hospital, Peking University, No. A59, Di'anmen West Street, Xicheng District, Beijing, 100034, China. xinzc@bjmu.edu.cn. 4. Department of Urology, First Affiliated Hospital of Soochow University, Soochow University, No. 188, Shizi Street, Gusu District, Suzhou, 215006, China. hjq0192@foxmail.com.
Abstract
PURPOSE: Erectile dysfunction (ED) is a distressing complication in men with diabetes mellitus (DM). This study aimed to investigate the effects of adipose-derived stem cells (ADSCs) plus insulin on ED in streptozotocin (STZ)-induced diabetic rats. METHODS: Forty-five eight-week-old male Sprague-Dawley rats received intraperitoneal injection of STZ (60 mg/kg). Eight weeks after the induction, the determined diabetic rats were randomly distributed into four groups: rats in DM + PBS group received a one-time intracavernous (IC) injection of phosphate-buffered saline (PBS) solution, DM + ADSCs group received IC injection of ADSCs, DM + Insulin group received subcutaneous injection of neutral protamine Hagedorn twice a day, and DM + ADSCs + Insulin group received both ADSCs and neutral protamine Hagedorn treatments. Another 10 normal rats were served as control group and received IC injection of PBS. Four weeks after the treatments, intracavernous pressure, histopathological changes in penis, functional proteins of ADSCs, and penis were measured. RESULTS: We found that ADSCs expressed vascular endothelial growth factor, TIMP metallopeptidase inhibitor 1 (TIMP-1), and lipopolysaccharide-inducible CXC chemokine (LIX). ADSC injection partially restored cavernous endothelium and smooth muscle contents and nNOS-positive nerves, and reduced apoptosis in penis compared with PBS-treated diabetic rats. Insulin treatment could further modulate inflammatory response and reduce advanced glycation end-product accumulation in penis. CONCLUSIONS: Better than single therapy, ADSCs combined with insulin ameliorate ED and pathological changes in diabetic rats to near-normal levels.
PURPOSE:Erectile dysfunction (ED) is a distressing complication in men with diabetes mellitus (DM). This study aimed to investigate the effects of adipose-derived stem cells (ADSCs) plus insulin on ED in streptozotocin (STZ)-induced diabeticrats. METHODS: Forty-five eight-week-old male Sprague-Dawley rats received intraperitoneal injection of STZ (60 mg/kg). Eight weeks after the induction, the determined diabeticrats were randomly distributed into four groups: rats in DM + PBS group received a one-time intracavernous (IC) injection of phosphate-buffered saline (PBS) solution, DM + ADSCs group received IC injection of ADSCs, DM + Insulin group received subcutaneous injection of neutral protamine Hagedorn twice a day, and DM + ADSCs + Insulin group received both ADSCs and neutral protamine Hagedorn treatments. Another 10 normal rats were served as control group and received IC injection of PBS. Four weeks after the treatments, intracavernous pressure, histopathological changes in penis, functional proteins of ADSCs, and penis were measured. RESULTS: We found that ADSCs expressed vascular endothelial growth factor, TIMP metallopeptidase inhibitor 1 (TIMP-1), and lipopolysaccharide-inducible CXC chemokine (LIX). ADSC injection partially restored cavernous endothelium and smooth muscle contents and nNOS-positive nerves, and reduced apoptosis in penis compared with PBS-treated diabeticrats. Insulin treatment could further modulate inflammatory response and reduce advanced glycation end-product accumulation in penis. CONCLUSIONS: Better than single therapy, ADSCs combined with insulin ameliorate ED and pathological changes in diabeticrats to near-normal levels.
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