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Digholkar G, Varghese R, Pal K, Sharma R. Adipose-derived stem cells: an upcoming novel therapeutic in the management of Erectile dysfunction post radical prostatectomy in prostate cancer patients. Int J Impot Res 2024; 36:818-819. [PMID: 38443556 DOI: 10.1038/s41443-024-00866-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 02/04/2024] [Accepted: 02/23/2024] [Indexed: 03/07/2024]
Affiliation(s)
- Gargi Digholkar
- Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be) University, Pune, Maharashtra, 411038, India
| | - Ryan Varghese
- Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be) University, Pune, Maharashtra, 411038, India
- Advanced Centre for Treatment, Research, and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra, 410210, India
- Homi Bhabha National Institute, Anushakti Nagar, Mumbai, Maharashtra, 400094, India
- Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, Saint Joseph's University, Philadelphia, PA, 19104, USA
| | - Kavita Pal
- Advanced Centre for Treatment, Research, and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra, 410210, India.
- Homi Bhabha National Institute, Anushakti Nagar, Mumbai, Maharashtra, 400094, India.
| | - Rohit Sharma
- Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India.
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Mazza M, Margoni S, Mandracchia G, Donofrio G, Fischetti A, Kotzalidis GD, Marano G, Simonetti A, Janiri D, Moccia L, Marcelli I, Sfratta G, De Berardis D, Ferrara O, Bernardi E, Restaino A, Lisci FM, D'Onofrio AM, Brisi C, Grisoni F, Calderoni C, Ciliberto M, Brugnami A, Rossi S, Spera MC, De Masi V, Marzo EM, Abate F, Boggio G, Anesini MB, Falsini C, Quintano A, Torresi A, Milintenda M, Bartolucci G, Biscosi M, Ruggiero S, Lo Giudice L, Mastroeni G, Benini E, Di Benedetto L, Caso R, Pesaresi F, Traccis F, Onori L, Chisari L, Monacelli L, Acanfora M, Gaetani E, Marturano M, Barbonetti S, Specogna E, Bardi F, De Chiara E, Stella G, Zanzarri A, Tavoletta F, Crupi A, Battisti G, Monti L, Camardese G, Chieffo D, Gasbarrini A, Scambia G, Sani G. This pain drives me crazy: Psychiatric symptoms in women with interstitial cystitis/bladder pain syndrome. World J Psychiatry 2024; 14:954-984. [PMID: 38984334 PMCID: PMC11230088 DOI: 10.5498/wjp.v14.i6.954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 04/22/2024] [Accepted: 05/07/2024] [Indexed: 06/19/2024] Open
Abstract
BACKGROUND Interstitial cystitis/bladder pain syndrome (IC/BPS) is an at least 6-mo noninfectious bladder inflammation of unknown origin characterized by chronic suprapubic, abdominal, and/or pelvic pain. Although the term cystitis suggests an inflammatory or infectious origin, no definite cause has been identified. It occurs in both sexes, but women are twice as much affected. AIM To systematically review evidence of psychiatric/psychological changes in persons with IC/BPS. METHODS Hypothesizing that particular psychological characteristics could underpin IC/BPS, we investigated in three databases the presence of psychiatric symptoms and/or disorders and/or psychological characteristics in patients with IC/BPS using the following strategy: ("interstitial cystitis" OR "bladder pain syndrome") AND ("mood disorder" OR depressive OR antidepressant OR depression OR depressed OR hyperthymic OR mania OR manic OR rapid cyclasterisk OR dysthymiasterisk OR dysphoriasterisk). RESULTS On September 27, 2023, the PubMed search produced 223 articles, CINAHL 62, and the combined PsycLIT/ PsycARTICLES/PsycINFO/Psychology and Behavioral Sciences Collection search 36. Search on ClinicalTrials.gov produced 14 studies, of which none had available data. Eligible were peer-reviewed articles reporting psychiatric/psychological symptoms in patients with IC/BPS, i.e. 63 articles spanning from 2000 to October 2023. These studies identified depression and anxiety problems in the IC/BPS population, along with sleep problems and the tendency to catastrophizing. CONCLUSION Psychotherapies targeting catastrophizing and life stress emotional awareness and expression reduced perceived pain in women with IC/BPS. Such concepts should be considered when implementing treatments aimed at reducing IC/BPS-related pain.
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Affiliation(s)
- Marianna Mazza
- Department of Neurosciences, Fondazione Policlinico Universitario A Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Stella Margoni
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Giuseppe Mandracchia
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Guglielmo Donofrio
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Alessia Fischetti
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | | | - Giuseppe Marano
- Department of Neurosciences, Fondazione Policlinico Universitario A Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Alessio Simonetti
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Delfina Janiri
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Lorenzo Moccia
- Department of Neurosciences, Section of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Ilaria Marcelli
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Greta Sfratta
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | | | - Ottavia Ferrara
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Evelina Bernardi
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Antonio Restaino
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | | | | | - Caterina Brisi
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Flavia Grisoni
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Claudia Calderoni
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Michele Ciliberto
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Andrea Brugnami
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Sara Rossi
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Maria Chiara Spera
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Valeria De Masi
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Ester Maria Marzo
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Francesca Abate
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Gianluca Boggio
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | | | - Cecilia Falsini
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Anna Quintano
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Alberto Torresi
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Miriam Milintenda
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Giovanni Bartolucci
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Marco Biscosi
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Sara Ruggiero
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Luca Lo Giudice
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Giulia Mastroeni
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Elisabetta Benini
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Luca Di Benedetto
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Romina Caso
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Francesco Pesaresi
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Francesco Traccis
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Luca Onori
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Luca Chisari
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Leonardo Monacelli
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Mariateresa Acanfora
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Eleonora Gaetani
- Medical and Surgical Sciences, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Monia Marturano
- Division of Gynecologic Oncology, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Sara Barbonetti
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Elettra Specogna
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Francesca Bardi
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Emanuela De Chiara
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Gianmarco Stella
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Andrea Zanzarri
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Flavio Tavoletta
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Arianna Crupi
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Giulia Battisti
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Laura Monti
- UOS Psicologia Clinica, Governo Clinico, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
| | - Giovanni Camardese
- Department of Psychiatry, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Daniela Chieffo
- UOS Psicologia Clinica, Governo Clinico, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
| | - Antonio Gasbarrini
- CEMAD Digestive Disease Center, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome 00168, Italy
| | - Giovanni Scambia
- Department of Woman and Child Health, Catholic University, Rome 00168, Italy
| | - Gabriele Sani
- UOC Psichiatria Clinica e d’Urgenza, Dipartimento di Scienze Dell’Invecchiamento, Neurologiche, Ortopediche e Della Testa-collo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
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Islam MM, Naveen NR, Anitha P, Goudanavar PS, Rao GSNK, Fattepur S, Rahman MM, Shiroorkar PN, Habeebuddin M, Meravanige G, Telsang M, Nagaraja S, Asdaq SMB, Anwer MDK. The Race to Replace PDE5i: Recent Advances and Interventions to Treat or Manage Erectile Dysfunction: Evidence from Patent Landscape (2016-2021). J Clin Med 2022; 11:jcm11113140. [PMID: 35683526 PMCID: PMC9181403 DOI: 10.3390/jcm11113140] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 05/18/2022] [Accepted: 05/29/2022] [Indexed: 02/01/2023] Open
Abstract
For a few decades, globally, erectile dysfunction (ED) has become more prominent even in young adults and represents a mounting health concern causing a significant effect on men’s quality of life. There is an expectation that by the end of 2025, the number of ED cases can rise to 322 million. We aimed to comprehensively analyze the scientific output of scholarly articles and studies in the field of ED (2016–2021). Data from scholarly articles were collected using Pubmed, and clinical trials-related information was accessed from the clinical trials website. An extensive patent search was conducted using databases such as USPTO (United States patent and trademark office) and EPO (European patent office), WIPO (World Intellectual Property Organization), etc. Owing to the high market value of ED drugs, considerable interest was attained to grab the opportunities. The race to replace the phosphodiesterase type 5 inhibitor (PDE5 inhibitor-PDE5i) can be identified as evident from the significant number of patents filed and the inventions cleared with clinical trials. Some other intriguing interventions are identified for ED treatment but have yet to gain public acceptance. The current analysis confirms the overall evolution and unexplored corners of research on ED treatment strategies with a current global projection.
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Affiliation(s)
- Mohammed Monirul Islam
- Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
- Correspondence: (M.M.I.); (N.R.N.); (S.F.)
| | - Nimbagal Raghavendra Naveen
- Department of Pharmaceutics, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, B.G. Nagar 571448, Karnataka, India
- Correspondence: (M.M.I.); (N.R.N.); (S.F.)
| | - Posina Anitha
- Department of Pharmaceutics, Annamacharya College of Pharmacy, New Boyanapalli, Rajampet 516126, Andhra Pradesh, India; (P.A.); (P.S.G.)
| | - Prakash S. Goudanavar
- Department of Pharmaceutics, Annamacharya College of Pharmacy, New Boyanapalli, Rajampet 516126, Andhra Pradesh, India; (P.A.); (P.S.G.)
| | - G. S. N. Koteswara Rao
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida 203201, Uttar Pradesh, India;
| | - Santosh Fattepur
- School of Pharmacy, Management and Science University, Seksyen 13, Shah Alam 40100, Selangor, Malaysia
- Correspondence: (M.M.I.); (N.R.N.); (S.F.)
| | - Muhammad Muhitur Rahman
- Department of Civil and Environmental Engineering, College of Engineering, King Faisal University, Al-Ahsa 31982, Saudi Arabia;
| | | | - Mohammed Habeebuddin
- Department of Biomedical Sciences, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia; (P.N.S.); (M.H.); (G.M.)
| | - Girish Meravanige
- Department of Biomedical Sciences, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia; (P.N.S.); (M.H.); (G.M.)
| | - Mallikarjun Telsang
- Department of Medicine, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia;
| | - Sreeharsha Nagaraja
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Hofuf, Al-Ahsa 31982, Saudi Arabia;
- Department of Pharmaceutics, Vidya Siri College of Pharmacy, Off Sarjapura Road, Bangalore 560035, Karnataka, India
| | | | - MD. Khalid Anwer
- Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Alkharj 11942, Saudi Arabia;
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He Z, Yin G, Li QQ, Zeng Q, Duan J. Diabetes Mellitus Causes Male Reproductive Dysfunction: A Review of the Evidence and Mechanisms. In Vivo 2021; 35:2503-2511. [PMID: 34410936 DOI: 10.21873/invivo.12531] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 06/09/2021] [Accepted: 06/15/2021] [Indexed: 01/05/2023]
Abstract
The metabolic disorders caused by diabetes can lead to various complications, including dysfunction of the male reproductive system. In patients with diabetes, long-term hyperglycemia results in diabetic vascular neuropathy, oxidative stress injury, abnormal zinc metabolism, and insulin resistance syndrome. In addition, insulin deficiency and resistance in diabetes can damage the hypothalamus, pituitary gland, gonads, and perigonads. This can reduce the secretion of sex hormones including gonadotropin-releasing hormone, follicle stimulating hormone, luteinizing hormone, and testosterone, and can lead to testicular atrophy, stromal cell atrophy, seminiferous tubule damage, spermatogenic cell damage, and other structural injuries of the male reproductive organs. These actions can affect male fertility and reproductive health. Herein, we review studies that report a causative role of diabetes in male reproductive function. We also discuss the evidence-based mechanisms involved in the processes of diabetes-related male sexual and reproductive dysfunction as well as the progress in treatment.
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Affiliation(s)
- Zubin He
- 924 Hospital of PLA Joint Logistic Support Force, Guilin, P.R. China
| | - Guochao Yin
- Guilin Rehabilitation and Recuperation Center, Guilin, P.R. China
| | - Qingdi Quentin Li
- Scientific Review Branch, Division of Extramural Research and Training, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC, U.S.A
| | - Qiongfang Zeng
- 924 Hospital of PLA Joint Logistic Support Force, Guilin, P.R. China
| | - Jinliang Duan
- 924 Hospital of PLA Joint Logistic Support Force, Guilin, P.R. China;
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Irdam GA, Febriyani, Rasyid N, Taher A. A systematic review of intracavernosal injection of mesenchymal stem cells for diabetic erectile dysfunction. MEDICAL JOURNAL OF INDONESIA 2021. [DOI: 10.13181/mji.oa.204475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
BACKGROUND As current erectile dysfunction (ED) treatments are limited, other treatment such as stem cells should be explored. Hence, this study aimed to review the sources, method of administration, and therapeutic effect of mesenchymal stem cells (MSCs) for diabetic ED treatment.
METHODS All relevant articles regarding the use of MSCs for diabetic ED were searched in PubMed and Google Scholar databases from December 15, 2019 to January 1, 2020 published in the past 10 years. The keywords were “mesenchymal stem cells” and “diabetic ED”. The selection and critical appraisal of the studies were discussed. Diabetic ED was evaluated for functional and structural outcome. Functional outcome in animal studies was assessed by intracavernosal pressure/mean arterial pressure (ICP/MAP) ratio, meanwhile the structural outcome was done microscopically. In human study, the assessments were done using international index of erectile function score (IIEF-5) to erection hardness score and penile Doppler ultrasonography.
RESULTS There were 10 animal studies and 3 human studies. The studies used MSCs from adipose (n = 6), bone marrow (n = 4), placenta (n = 1), umbilical cord (n = 1), and muscle tissue (n = 1). The MSCs were administrated through intracavernosal injection in all studies. In all animal studies, functional outcome was improved, shown in higher ICP/MAP ratio. Microscopically, there were an increase of cavernosal endothelial cells, vascular endothelial growth factor, nitric oxide synthase, and smooth muscle cells. In human studies, IIEF-5 and erection hardness score were improved. Peak systolic velocity was also higher.
CONCLUSIONS MSCs may be a promising therapy for diabetic ED; however, long-term safety concerns still need further investigations.
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Grice PT, Liu J, Gabrielson AT, Pearce I, Bivalacqua TJ, Modgil V. Drug delivery options and therapeutic advances in the management of erectile dysfunction. Expert Opin Drug Deliv 2020; 17:1259-1268. [PMID: 32531183 DOI: 10.1080/17425247.2020.1782383] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Erectile dysfunction (ED) is defined as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance. It is estimated that 20-30% of adult men will have at least one episode of ED during their lifetime and the prevalence increases with age. ED is known to have significant negative psychological implications for men, resulting in impaired functional status and a greater prevalence of anxiety and depression. AREAS COVERED Medications for the treatment of erectile dysfunction largely revolve around oral, injection, and topical therapies. Though all three modalities are widely used, each delivery option has its own advantages and specific indications. Likewise, there are several new developing treatments for ED that may change the landscape of treatment. The goal of this review is to summarize contemporary drug delivery options used in the treatment of ED and highlight future promising pharmacological developments. EXPERT OPINION There are a myriad of new developments on the horizon including new PDE5Is and drug targets, nanotechnology enhancements, stem cell and gene therapy, shockwave therapy, and platelet-rich plasma injections. These are all promising new methods to not only treat ED but also to address the pathology and prevent or eliminate further damage.
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Affiliation(s)
- P T Grice
- Nottingham Urology Centre, Nottingham University Hospitals NHS Trust , Nottingham, UK
| | - J Liu
- James Buchanan Brady Urological Institute, Johns Hopkins Hospital , Baltimore, Maryland, United States
| | - A T Gabrielson
- James Buchanan Brady Urological Institute, Johns Hopkins Hospital , Baltimore, Maryland, United States
| | - I Pearce
- Manchester Andrology Centre, Manchester Royal Infirmary, Manchester University Hospitals NHS Foundation Trust , UK
| | - T J Bivalacqua
- James Buchanan Brady Urological Institute, Johns Hopkins Hospital , Baltimore, Maryland, United States
| | - V Modgil
- Manchester Andrology Centre, Manchester Royal Infirmary, Manchester University Hospitals NHS Foundation Trust , UK
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Liu Y, Zhao S, Luo L, Wang J, Zhu Z, Xiang Q, Deng Y, Zhao Z. Mesenchymal stem cell-derived exosomes ameliorate erection by reducing oxidative stress damage of corpus cavernosum in a rat model of artery injury. J Cell Mol Med 2019; 23:7462-7473. [PMID: 31512385 PMCID: PMC6815831 DOI: 10.1111/jcmm.14615] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 08/01/2019] [Accepted: 08/09/2019] [Indexed: 12/13/2022] Open
Abstract
Erectile dysfunction (ED) is a common ageing male's disease, and vascular ED accounts for the largest proportion of all types of ED. One of the mechanisms of vascular ED in the clinic is arterial insufficiency, which mainly caused by atherosclerosis, trauma and surgical. Moreover, oxidative stress damage after tissue ischemia usually aggravated the progress of ED. As a new way of acellular therapy, mesenchymal stem cell-derived exosomes (MSC-Exos) have great potential in ED treatment. In the current study, we have explored the mechanism of MSC-Exos therapy in a rat model of internal iliac artery injury-induced ED. Compared with intracavernous (IC) injection of phosphate-buffered saline after artery injury, of note, we observed that both mesenchymal stem cells (MSCs) and MSC-Exos through IC injection could improve the erectile function to varying degrees. More specifically, IC injection MSC-Exos could promote cavernous sinus endothelial formation, reduce the organization oxidative stress damage, and improve the nitric oxide synthase and smooth muscle content in the corpus cavernosum. With similar potency compared with the stem cell therapy and other unique advantages, IC injection of MSC- Exos could be an effective treatment to ameliorate erectile function in a rat model of arterial injury.
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Affiliation(s)
- Yangzhou Liu
- Department of Urology & Andrology, Minimally Invasive Surgery Center, Guangdong Provincial Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Shankun Zhao
- Department of Urology & Andrology, Minimally Invasive Surgery Center, Guangdong Provincial Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Department of Urology, Zhejiang Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Lianmin Luo
- Department of Urology & Andrology, Minimally Invasive Surgery Center, Guangdong Provincial Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Jiamin Wang
- Department of Urology & Andrology, Minimally Invasive Surgery Center, Guangdong Provincial Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Zhiguo Zhu
- Department of Urology & Andrology, Minimally Invasive Surgery Center, Guangdong Provincial Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Qian Xiang
- Department of Urology & Andrology, Minimally Invasive Surgery Center, Guangdong Provincial Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yihan Deng
- Department of Urology & Andrology, Minimally Invasive Surgery Center, Guangdong Provincial Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Zhigang Zhao
- Department of Urology & Andrology, Minimally Invasive Surgery Center, Guangdong Provincial Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
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Haahr MK, Harken Jensen C, Toyserkani NM, Andersen DC, Damkier P, Sørensen JA, Sheikh SP, Lund L. A 12-Month Follow-up After a Single Intracavernous Injection of Autologous Adipose-Derived Regenerative Cells in Patients with Erectile Dysfunction Following Radical Prostatectomy: An Open-Label Phase I Clinical Trial. Urology 2018; 121:203.e6-203.e13. [PMID: 29958973 DOI: 10.1016/j.urology.2018.06.018] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Revised: 05/30/2018] [Accepted: 06/11/2018] [Indexed: 12/24/2022]
Abstract
OBJECTIVE To explore safety in adipose-derived regenerative cells (ADRC) therapy, treating erectile dysfunction (ED). METHODS Twenty-one patients with ED after radical prostatectomy, with no signs of recovery using conventional therapy, received a single intracavernous injection of autologous ADRC and were followed for 1 year. Six men were incontinent, and 15 were continent at inclusion. The primary (safety of ADRC therapy) and secondary endpoints (sexual function) were evaluated at 1, 3, 6, and 12 months after ADRC injection by registration of adverse events and validated questionnaires using the international index of erectile function-5 and erection hardness score. RESULTS No serious adverse events occurred, but 8 reversible minor events related to the liposuction were noted. Eight out of 15 (53%) patients in the continent group reported erectile function sufficient for intercourse at 12 months. Baseline median international index of erectile function-5 scores (6.0; interquartile range [IQR] 3) were unchanged 1 month after the treatment, but significantly increased after 6 to 7 (IQR 17). This effect was sustained at 12 months (median 8; IQR 14). We did not see any improvements in erectile function in the group of incontinent men or among men with ED prior to radical prostatectomy. CONCLUSION Intracavernous injection of ADRC is safe in this phase 1 study with a 12-month follow-up.
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Affiliation(s)
- Martha Kirstine Haahr
- Department of Urology, Odense University Hospital, Odense, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com), Odense University Hospital, Odense, Denmark; Clinical Institute, University of Southern Denmark, Odense, Denmark.
| | - Charlotte Harken Jensen
- Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark
| | - Navid Mohamadpour Toyserkani
- Department of Plastic Surgery, Odense University Hospital, Odense, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com), Odense University Hospital, Odense, Denmark
| | - Ditte Caroline Andersen
- Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com), Odense University Hospital, Odense, Denmark
| | - Per Damkier
- Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark
| | - Jens Ahm Sørensen
- Department of Plastic Surgery, Odense University Hospital, Odense, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com), Odense University Hospital, Odense, Denmark
| | - Søren Paludan Sheikh
- Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark; Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com), Odense University Hospital, Odense, Denmark
| | - Lars Lund
- Department of Urology, Odense University Hospital, Odense, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com), Odense University Hospital, Odense, Denmark; Clinical Institute, University of Southern Denmark, Odense, Denmark
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Gene Delivery Approaches for Mesenchymal Stem Cell Therapy: Strategies to Increase Efficiency and Specificity. Stem Cell Rev Rep 2017; 13:725-740. [DOI: 10.1007/s12015-017-9760-2] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Mobley DF, Khera M, Baum N. Recent advances in the treatment of erectile dysfunction. Postgrad Med J 2017; 93:679-685. [PMID: 28751439 DOI: 10.1136/postgradmedj-2016-134073] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Revised: 02/21/2017] [Accepted: 04/23/2017] [Indexed: 01/01/2023]
Abstract
Erectile dysfunction (ED) is one of the most common conditions affecting middle-aged and older men. Nearly every primary care physician, internist and geriatrician will be called upon to manage this condition or to make referrals to urologists, endocrinologists and cardiologists who will assist in the treatment of ED. This article will briefly discuss the diagnosis and management of ED. In addition, emerging concepts in ED management will be discussed, such as the use of testosterone to treat ED, the role of the endothelium in men with ED and treating the partner of the man with ED. Finally, future potential therapies for ED will be discussed.
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Affiliation(s)
- David F Mobley
- Department of Urology, Weill-Cornell Medicine, Houston, Texas, USA
| | - Mohit Khera
- Department of Urology, Baylor College of Medicine, Houston, Texas, USA
| | - Neil Baum
- Department of Urology, Tulane Medical School, New Orleans, Louisiana, USA
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Reed-Maldonado AB, Lue TF. The Current Status of Stem-Cell Therapy in Erectile Dysfunction: A Review. World J Mens Health 2016; 34:155-164. [PMID: 28053944 PMCID: PMC5209555 DOI: 10.5534/wjmh.2016.34.3.155] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2016] [Revised: 07/18/2016] [Accepted: 08/08/2016] [Indexed: 12/13/2022] Open
Abstract
Stem cells are undifferentiated cells that are capable of renewal and repair of tissue due to their capacity for division and differentiation. The purpose of this review is to describe recent advances in the use of stem cell (SC) therapy for male erectile dysfunction (ED). We performed a MEDLINE database search of all relevant articles regarding the use of SCs for ED. We present a concise summary of the scientific principles behind the usage of SC for ED. We discuss the different types of SCs, delivery methods, current pre-clinical literature, and published clinical trials. Four clinical trials employing SC for ED have been published. These articles are summarized in this review. All four report improvements in ED after SC therapy. SC therapy remains under investigation for the treatment of ED. It is reassuring that clinical trials thus far have reported positive effects on erectile function and few adverse events. Safety and methodical concerns about SC acquisition, preparation and delivery remain and require continued investigation prior to wide-spread application of these methods.
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Affiliation(s)
| | - Tom F Lue
- Department of Urology, University of California San Francisco, CA, USA
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Haahr MK, Jensen CH, Toyserkani NM, Andersen DC, Damkier P, Sørensen JA, Lund L, Sheikh SP. Safety and Potential Effect of a Single Intracavernous Injection of Autologous Adipose-Derived Regenerative Cells in Patients with Erectile Dysfunction Following Radical Prostatectomy: An Open-Label Phase I Clinical Trial. EBioMedicine 2016; 5:204-10. [PMID: 27077129 PMCID: PMC4816754 DOI: 10.1016/j.ebiom.2016.01.024] [Citation(s) in RCA: 125] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2015] [Revised: 01/12/2016] [Accepted: 01/18/2016] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Prostate cancer is the most common cancer in men, and radical prostatectomy (RP) often results in erectile dysfunction (ED) and a substantially reduced quality of life. The efficacy of current interventions, principal treatment with PDE-5 inhibitors, is not satisfactory and this condition presents an unmet medical need. Preclinical studies using adipose-derived stem cells to treat ED have shown promising results. Herein, we report the results of a human phase 1 trial with autologous adipose-derived regenerative cells (ADRCs) freshly isolated after a liposuction. METHODS Seventeen men suffering from post RP ED, with no recovery using conventional therapy, were enrolled in a prospective phase 1 open-label and single-arm study. All subjects had RP performed 5-18 months before enrolment, and were followed for 6 months after intracavernosal transplantation. ADRCs were analyzed for the presence of stem cell surface markers, viability and ability to differentiate. Primary endpoint was the safety and tolerance of the cell therapy while the secondary outcome was improvement of erectile function. Any adverse events were reported and erectile function was assessed by IIEF-5 scores. The study is registered with ClinicalTrials.gov, NCT02240823. FINDINGS Intracavernous injection of ADRCs was well-tolerated and only minor events related to the liposuction and cell injections were reported at the one-month evaluation, but none at later time points. Overall during the study period, 8 of 17 men recovered their erectile function and were able to accomplish sexual intercourse. Post-hoc stratification according to urinary continence status was performed. Accordingly, for continent men (median IIEFinclusion = 7 (95% CI 5-12), 8 out of 11 men recovered erectile function (IIEF6months = 17 (6-23)), corresponding to a mean difference of 0.57 (0.38-0.85; p = 0.0069), versus inclusion. In contrast, incontinent men did not regain erectile function (median IIEF1/3/6 months = 5 (95% CI 5-6); mean difference 1 (95% CI 0.85-1.18), p > 0.9999). INTERPRETATION In this phase I trial a single intracavernosal injection of freshly isolated autologous ADRCs was a safe procedure. A potential efficacy is suggested by a significant improvement in IIEF-5 scores and erectile function. We suggest that ADRCs represent a promising interventional therapy of ED following prostatectomy. FUNDING Danish Medical Research Council, Odense University Hospital and the Danish Cancer Society.
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Key Words
- ADRC, adipose-derived regenerative cells
- Adipose-derived regenerative cells
- Adipose-derived stem cells
- Adipose-derived stromal vascular fraction
- BMI, body mass index
- CFU-F, fibroblastoid colony forming units
- Cell therapy
- Clinical trial
- ED, erectile dysfunction
- EHS, erection hardness score
- Erectile dysfunction
- ICIQ-UI SF, incontinence questionnaire – urinary incontinence – short form questionnaire
- IIEF-5, international index of erectile function-5
- LUTS, lower urinary tract symptoms
- NSAID, nonsteroidal antiinflammatory drug
- PDE-5, phosphodiesterase-5
- RP, radical prostatectomy
- SVF, stromal vascular fraction
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Affiliation(s)
- Martha Kirstine Haahr
- Department of Urology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com); Odense University Hospital, Denmark; Clinical Institute, University of Southern Denmark, 5000 Odense C, Denmark
| | - Charlotte Harken Jensen
- Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com); Odense University Hospital, Denmark
| | - Navid Mohamadpour Toyserkani
- Department of Plastic Surgery, Odense University Hospital, Odense, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com); Odense University Hospital, Denmark; Clinical Institute, University of Southern Denmark, 5000 Odense C, Denmark
| | - Ditte Caroline Andersen
- Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com); Odense University Hospital, Denmark; Clinical Institute, University of Southern Denmark, 5000 Odense C, Denmark
| | - Per Damkier
- Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark; Clinical Institute, University of Southern Denmark, 5000 Odense C, Denmark
| | - Jens Ahm Sørensen
- Department of Plastic Surgery, Odense University Hospital, Odense, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com); Odense University Hospital, Denmark; Clinical Institute, University of Southern Denmark, 5000 Odense C, Denmark
| | - Lars Lund
- Department of Urology, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com); Odense University Hospital, Denmark; Clinical Institute, University of Southern Denmark, 5000 Odense C, Denmark
| | - Søren Paludan Sheikh
- Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark; Institute of Molecular Medicine, University of Southern Denmark, Winsloewparken 21 3rd, 5000 Odense C, Denmark; The Danish Centre for Regenerative Medicine (www.danishcrm.com); Odense University Hospital, Denmark
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