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Stem cell-derived exosomes as a therapeutic tool for cardiovascular disease

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World Journal of Stem Cells 2016年第9期8卷 297-305页

作者： etsu Suzuki Daishi Fujita Masao Takahashi Shigeyoshi Oba Hiroaki Nishimatsu Institute of Medical Science St. Marianna University School of Medicine Department of Internal Medicine Faculty of Medicine University of Tokyo Department of Urology Faculty of MedicineUniversity of Tokyo

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.

关键词： Exosomes Messenger RNA Cardiovascular disease Mesenchymal stem cells Stem cells MicroRNA

Theta Activity in the Regio Inferior of the Temporal Hippocampus by Odor Stimulation in Anesthetized Pigs

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Open Journal of Animal Sciences 2017年第4期7卷 365-375页

作者： Toshiyuki Saito Sei-etsu Fujiwara Takashi Yamaguchi Faculty of Life Sciences Kyoto Sangyo University Kyoto Japan National Institute of Agrobiological Sciences Tsukuba Japan School of Medicine St. Marianna University Kawasaki Japan Graduate School of Science and Engineering Yamagata University Yonezawa Japan

We examined theta activity in the temporal hippocampus of ure-thane-chloralose-anesthetized pigs by stimulation with two chemical odors, beta-phenyl ethyl alcohol (PEA;rose-like odor) and n-amyl acetate (banana-like odor). Neural activity was recorded in the neural cell layer nearby fimbria of the temporal hippocampus in three of six animals. Odor stimulation with PEA at a low concentration (10-4 w/w;100 ppm) significantly increased power of the low-frequency theta band (type-2;4 - 6 Hz) for the middle 10 s (w (3, 6, 2.5%) >2.56). The PEA odor at a higher concentration (10-3 w/w;1000 ppm), however, showed a tendency for gradual increase in?the low-frequency theta but the response was insignificant compared with the control. On the other hand, odor stimulation with n-amyl acetate (10-4 w/w;100 ppm) caused no apparent increase or a tendency for decrease in power of the low-frequency theta. Thus, the type-2 theta response in the temporal hippocampus to the PEA odor contrasted strikingly with that to the n-amylacetate in the ure-thane-chloralose-anesthetized pigs. The response of the type-2 theta rhythm in the temporal hippocampus may underlie the difference in emotional sensation and cognition of PEA from n-amyl acetate in the pig.

关键词： Fast Fourier Transform Rhythmic Oscillations Sus scrofa domesticus

The effect of exercise on dopaminergic brain functions

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The effect of exercise on dopaminergic brain functions

Adult stem cells as a tool for kidney regeneration

第十五届国际药理学大会

作者： Sutoo Den’ etsu Akiyama Kayo Institute of Medical Science University of TsukubaTsukuba 305-8575Japan Institute of Medical Science University of TsukubaTsukuba 305-8575Japan

＜正＞ The effect of exercise on brain function was investigated through animal experiments . Previous our studies indicated that calcium increases brain dopamine （DA） synthesis through a calmodu lin- dependent *** leads to increased serum calcium levels,and the calcium is transported to the brain. This in turn enhances brain DA synthesis,and increased DA levels regulate various brain functions. There are abnormally low levels of DA in the neos-triatum and nucleus accumbens of epileptic mice （El mice） and spontaneously hypertensive rats （SHR）. The low DA levels in those animals were improved following intracerebroventricular administration of calcium chloride. Blood pressure and DA levels in SHR were also normalized by exercise. In epileptic El mice,convulsions normalized DA levels and physiologic function. These findings suggest that exercise or convulsions affect various brain functions through calcium -dependent DA synthesis. This leads to the possibility that symptoms in various diseases that involve DA dysfunction such as Parkinson’s disease or senile dementia might be improved by exercise. Ref.: Neurobiol. Dis. 13: 1-14. 2003.

关键词： calcium/calmodulin dopamine synthesis exercise.

来源： cnki会议评论

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World Journal of Nephrology 2016年第1期5卷 43-52页

作者： etsu Suzuki Daishi Fujita Masao Takahashi Shigeyoshi Oba Hiroaki Nishimatsu Institute of Medical Science St. Marianna Univer- sity School of Medicine Department of Internal Medicine Faculty of Medicine University of Tokyo Department of Urology Faculty of Medicine University of Tokyo

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.

关键词：肾脏再生成体干细胞治疗方法临床分析

向往的世界是怎样的世界呢?——“不在此地,不在别处”展前言

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天津美术学院学报 2016年第2期 30-37页

作者：江上越中央美术学院

元典美术馆于2016年1月12日开幕的展览"不在此地,不在别处",是一个集结了中国年轻艺术家作品的展览。这些作品都指向一个相对集中的话题,即"身份"。身处不同地域,艺术家自身携带的身份信息就自然流露出来,形成差异、多元的现象,正如今... 详细信息

元典美术馆于2016年1月12日开幕的展览"不在此地,不在别处",是一个集结了中国年轻艺术家作品的展览。这些作品都指向一个相对集中的话题,即"身份"。身处不同地域,艺术家自身携带的身份信息就自然流露出来,形成差异、多元的现象,正如今天世界的缩影。在此,本刊将此展览的前言与作品一并呈现给读者,弥补未到现场观看的观众的遗憾。

关键词：世界前言向往艺术家展览美术馆作品中国年

Stem cell therapy for erectile dysfunction

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World Journal of Clinical Urology 2014年第3期3卷 272-282页

作者： etsu Suzuki Hiroaki Nishimatsu Yukio Homma Institute of Medical Science St. Marianna University School of MedicineMiyamae-kuKawasaki 216-8512 Japan The Department of Urology Faculty of Medicine University of TokyoBunkyo-kuTokyo 113-8655 Japan

Erectile dysfunction(ED)is an important health problem that has commonly been clinically treated using phosphodiesterase type 5 inhibitors(PDE5Is).However,PDE5Is are less effective when the structure of the cavernous body has been severely injured,and thus regeneration is *** cell therapy has been investigated as a possible means for regenerating the injured cavernous *** cells are classified into embryonic stem cells and adult stem cells(ASCs),and the intracavernous injection of ASCs has been explored as a therapy in animal ED *** marrowderived mesenchymal stem cells and adipose tissuederived stem cells are major sources of ASCs used for the treatment of ED,and accumulated evidence now suggests that ASCs are useful in the restoration of erectile function and the regeneration of the cavernous ***,the mechanisms by which ASCs recover erectile function remain *** studies indicated that ASCs were differentiated into the vascular endothelial cells,vascular smooth muscle cells,and nerve cells that originally resided in the cavernous body,whereas other studies have suggested that ASCs improved erectile function via the secretion of anti-apoptotic and/or proangiogenic cytokines ratherthan differentiation into other cell *** this paper,we reviewed the characteristics of stem cells used for the treatment of ED,and the possible mechanisms by which these cells exert their *** also discussed the problems to be solved before implementation in the clinical setting.

关键词： Erectile dysfunction Stem cell therapy Bone marrow-derived mesenchymal stem cells Adipose tissue-derived stem cells Endothelial progenitor cells Adrenomedullin Angiopoietin-1

Chronic kidney disease and erectile dysfunction

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World Journal of Nephrology 2014年第4期3卷 220-229页

作者： etsu Suzuki Hiroaki Nishimatsu Shigeyoshi Oba Masao Takahashi Yukio Homma Institute of Medical Science St.Marianna University School of Medicine The Department of Urology Faculty of MedicineUniversity of Tokyo The Department of Internal Medicine Faculty of MedicineUniversity of Tokyo

Erectile dysfunction(ED) is a common condition among male chronic kidney disease(CKD) *** prevalence is estimated to be approximately 80% among these *** 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 *** affecting these pathways can induce *** etiology of ED in CKD patients is *** 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 *** improvement of general conditions is the first step of *** dialysis and adequate nutritional intake are *** addition,control of anemia and secondary hyperparathyroidism is *** of drugs that potentially affect erectile function may be ***,zinc supplementation may be necessary whenzinc deficiency is *** type 5 inhibitors(PDE5Is) are commonly used for treating ED in CKD patients,and their efficacy was confirmed by many *** replacement therapy in addition to PDE5 Is may be useful,particularly for CKD patients with *** transplantation may restore erectile *** 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.

关键词：勃起功能障碍慢性肾病治疗方法临床分析

Adipose tissue-derived stem cells as a therapeutic tool for cardiovascular disease

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World Journal of Cardiology 2015年第8期7卷 454-465页

作者： etsu Suzuki Daishi Fujita Masao Takahashi Shigeyoshi Oba Hiroaki Nishimatsu Institute of Medical Science St. Marianna University School of Medicine the Department of Internal Medicine Faculty of Medicine University of Tokyo the Department of Urology Faculty of Medicine University of Tokyo

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.

关键词： Adipose tissue-derived stem cells Cardio-vascular disease Acute myocardial infarction Ischemic cardiomyopathy Hindlimb ischemia Stroke