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| 1 | Stem cell-derived exosomes as a therapeutic tool for cardiovascular disease显示文摘Mesenchymal stem cells(MSCs) have been used to treat patients suffering from acute myocardial infarction(AMI) and subsequent heart failure. Although it was originally assumed that MSCs differentiated into heart cells such as cardiomyocytes, recent evidence suggests that the differentiation capacity of MSCs is minimal and that injected MSCs restore cardiac function via the secretion of paracrine factors. MSCs secrete paracrine factors in not only naked forms but also membrane vesicles including exosomes containing bioactive substances such as proteins, messenger RNAs, and microR NAs. Although the details remain unclear, these bioactive molecules are selectively sorted in exosomes that are then released from donor cells in a regulated manner. Furthermore, exosomes are specifically internalized by recipient cells via ligand-receptor interactions. Thus, exosomes are promising natural vehicles that stably and specifically transport bioactive molecules to recipient cells. Indeed, stem cell-derived exosomes have been successfully used to treat cardiovascular disease(CVD), such as AMI, stroke, and pulmonary hypertension, in animal models, and their efficacy has been demonstrated. Therefore, exosome administration may be a promising strategy for the treatment of CVD. Furthermore, modifications of exosomal contents may enhance their therapeutic effects. Future clinical studies are required to confirm the efficacy of exosome treatment for CVD. | Etsu Suzuki Daishi Fujita Masao Takahashi Shigeyoshi Oba Hiroaki Nishimatsu | 2016 | World Journal of Stem Cells2016，8，9： | 19 |
| 2 | Adipose tissue-derived stem cells as a therapeutic tool for cardiovascular disease显示文摘Adipose tissue-deried stem cells( ADSCs) are adult stem cells that can be easily harvested from subcutaneous adipose tissue. Many studies have demonstrated that ADSCs differentiate into vascular endothelial cells(VECs), vascular smooth muscle cells(VSMCs), and cardiomyocytes in vitro and in vivo. However, ADSCs may fuse with tissue-resident cells and obtain the corresponding characteristics of those cells. If fusion occurs, ADSCs may express markers of VECs, VSMCs, and cardiomyocytes without direct differentiation into these cell types. ADSCs also produce a variety of paracrine factors such as vascular endothelial growth factor, hepatocyte growth factor, and insulin-like growth factor-1 that have proangiogenic and/or antiapoptotic activities. Thus, ADSCs have the potential to regenerate the cardiovascular system via direct differentiation into VECs, VSMCs, and cardiomyocytes, fusion with tissueresident cells, and the production of paracrine factors. Numerous animal studies have demonstrated the efficacy of ADSC implantation in the treatment of acute myocardial infarction(AMI), ischemic cardiomyopathy(ICM), dilated cardiomyopathy, hindlimb ischemia, and stroke. Clinical studies regarding the use of autologous ADSCs for treating patients with AMI and ICM have recently been initiated. ADSC implantation has been reported as safe and effective so far. Therefore, ADSCs appear to be useful for the treatment of cardiovascular disease. However, the tumorigenic potential of ADSCs requires careful evaluation before their safe clinical application. | Etsu Suzuki Daishi Fujita Masao Takahashi Shigeyoshi Oba Hiroaki Nishimatsu | 2015 | World Journal of Cardiology2015，7，8： | 17 |
| 3 | Chronic kidney disease and erectile dysfunction显示文摘Erectile dysfunction(ED) is a common condition among male chronic kidney disease(CKD) patients.Its prevalence is estimated to be approximately 80% among these patients.It has been well established that the production of nitric oxide from the cavernous nerve and vascular endothelium and the subsequent production of cyclic GMP are critically important in initiating and maintaining erection.Factors affecting these pathways can induce ED.The etiology of ED in CKD patients is multifactorial.Factors including abnormalities in gonadal-pituitary system,disturbance in autonomic nervous system,endothelial dysfunction,anemia(and erythropoietin deficiency),secondary hyperparathyroidism,drugs,zinc deficiency,and psychological problems are implicated in the occurrence of ED.An improvement of general conditions is the first step of treatment.Sufficient dialysis and adequate nutritional intake are necessary.In addition,control of anemia and secondary hyperparathyroidism is required.Changes of drugs that potentially affect erectile function may be necessary.Further,zinc supplementation may be necessary whenzinc deficiency is suspected.Phosphodiesterase type 5 inhibitors(PDE5Is) are commonly used for treating ED in CKD patients,and their efficacy was confirmed by many studies.Testosterone replacement therapy in addition to PDE5 Is may be useful,particularly for CKD patients with hypogonadism.Renal transplantation may restore erectile function.ED is an early marker of cardiovascular disease(CVD),which it frequently precedes; therefore,it is crucial to examine the presence of ED in CKD patients not only for the improvement of the quality of life but also for the prevention of CVD attack. | Etsu Suzuki Hiroaki Nishimatsu Shigeyoshi Oba Masao Takahashi Yukio Homma | 2014 | World Journal of Nephrology2014，3，4： | 3 |
| 4 | Renoprotective effect of erytbro- poietin in ischemia/reperfusion injury: Possible roles of the Akt/endothelial nitric oxide synthase - dependent pathway 显示文摘 | Shigeyoshi Oba Etsu Suzuki Hiroaki Nishimatsu | 2012 | International Journal of Urology2012，19，： | 1 |
| 5 | Adult stem cells as a tool for kidney regeneration显示文摘Kidney regeneration is a challenging but promising strategy aimed at reducing the progression to end-stage renal disease(ESRD) and improving the quality of life of patients with ESRD. Adult stem cells are multipotent stem cells that reside in various tissues, such as bone marrow and adipose tissue. Although intensive studies to isolate kidney stem/progenitor cells from the adult kidney have been performed, it remains controversial whether stem/progenitor cells actually exist in the mammalian adult kidney. The efficacy of mesenchymal stem cells(MSCs) in the recovery of kidney function has been demonstrated in animal nephropathy models, such as acute tubular injury, glomerulonephritis, renal artery stenosis, and remnant kidney. However, their beneficial effects seem to be mediated largely via their paracrine effects rather than their direct differentiation into renal parenchymal cells. MSCs not only secrete bioactive molecules directly into the circulation, but they also release various molecules, such as proteins, m RNA, and micro RNA, in membrane-covered vesicles. A detailed analysis of these molecules and an exploration of the optimal combination of these molecules will enable the treatment of patients with kidney disease without using stem cells. Another option for the treatment of patients with kidney disease using adult somatic cells is a direct/indirect reprogramming of adult somatic cells into kidney stem/progenitor cells. Although many hurdles still need to be overcome, this strategy will enable bona fide kidney regeneration rather than kidney repair using remnant renal parenchymal cells. | Etsu Suzuki Daishi Fujita Masao Takahashi Shigeyoshi Oba Hiroaki Nishimatsu | 2016 | World Journal of Nephrology2016，5，1： | 1 |
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