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      Concise Review: Tissue Engineering of Urinary Bladder; We Still Have a Long Way to Go?

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          Abstract

          Regenerative medicine is a new branch of medicine based on tissue engineering technology. This rapidly developing field of science offers revolutionary treatment strategy aimed at urinary bladder regeneration. Despite many promising announcements of experimental urinary bladder reconstruction, there has been a lack in commercialization of therapies based on current investigations. This is due to numerous obstacles that are slowly being identified and precisely overcome. The goal of this review is to present the current status of research on urinary bladder regeneration and highlight further challenges that need to be gradually addressed. We put an emphasis on expectations of urologists that are awaiting tissue engineering based solutions in clinical practice. This review also presents a detailed characteristic of obstacles on the road to successful urinary bladder regeneration from urological clinician perspective. A defined interdisciplinary approach might help to accelerate planning transitional research tissue engineering focused on urinary tracts. S tem C ells T ranslational M edicine 2017;6:2033–2043

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          Most cited references95

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          EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines.

          The European Association of Urology (EAU) guidelines panel on Muscle-invasive and Metastatic bladder cancer (BCa) updates its guidelines yearly. This updated summary provides a synthesis of the 2013 guidelines document, with emphasis on the latest developments. To provide graded recommendations on the diagnosis and treatment of patients with muscle-invasive BCa (MIBC), linked to a level of evidence. For each section of the guidelines, comprehensive literature searches covering the past 10 yr in several databases were conducted, scanned, reviewed, and discussed both within the panel and with external experts. The final results are reflected in the recommendations provided. Smoking and work-related carcinogens remain the most important risk factors for BCa. Computed tomography (CT) and magnetic resonance imaging can be used for staging, although CT is preferred for pulmonary evaluation. Open radical cystectomy with an extended lymph node dissection (LND) remains the treatment of choice for treatment failures in non-MIBC and T2-T4aN0M0 BCa. For well-informed, well-selected, and compliant patients, however, multimodality treatment could be offered as an alternative, especially if cystectomy is not an option. Comorbidity, not age, should be used when deciding on radical cystectomy. Patients should be encouraged to actively participate in the decision-making process, and a continent urinary diversion should be offered to all patients unless there are specific contraindications. For fit patients, cisplatinum-based neoadjuvant chemotherapy should always be discussed, since it improves overall survival. For patients with metastatic disease, cisplatin-containing combination chemotherapy is recommended. For unfit patients, carboplatin combination chemotherapy or single agents can be used. This 2013 EAU Muscle-invasive and Metastatic BCa guidelines updated summary aims to increase the quality of care and outcome for patients with muscle-invasive or metastatic BCa. In this paper we update the EAU guidelines on Muscle-invasive and Metastatic bladder cancer. We recommend that chemotherapy be administered before radical treatment and that bladder removal be the standard of care for disease confined to the bladder. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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            Effect of the Microenvironment on Mesenchymal Stem Cell Paracrine Signaling: Opportunities to Engineer the Therapeutic Effect.

            Cues from the extracellular environment, including physical stimuli, are well known to affect mesenchymal stem cell (MSC) properties in terms of proliferation and differentiation. Many therapeutic strategies are now targeting this knowledge to increase the efficacy of cell therapies, typically employed to repair tissue functions in the event of injury, either by direct engraftment into the target tissue or differentiation into mature tissues. However, it is now envisioned that harnessing the repertoire of factors secreted by MSCs (termed the secretome) may provide an alternate to these cell therapies. Of current interest are both direct protein secretions and two major subpopulations of bioactive extracellular vesicles (EVs), namely exosomes and microvesicles. EVs released by MSCs are reflective of their cells of origin, able to impact upon the activities of other cells in the local microenvironment, making the rational design of MSC paracrine activities an encouraging strategy to reproducibly modulate cell therapies. The precise mechanisms by which the secretome is modulated by the microenvironment, however, remain elusive. Controlling MSC growth conditions with oxygen tension, growth factor composition, and mechanical properties may serve to directly influence paracrine activity. Our growing understanding implicates components of the mechanotransduction machinery in translating both mechanical and chemical cues from the environment into alterations in gene regulation and varied paracrine activity. As technologies are developed to manufacture MSCs, advances in bioengineering and novel insight of how the extracellular environment affects MSC paracrine activity will play a pivotal role in the generation of widespread, successful, clinical MSC therapies.
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              Urine derived cells are a potential source for urological tissue reconstruction.

              Contemporary approaches to tissue engineering and cell therapy for urinary tract reconstruction require invasive tissue biopsies to obtain autologous cells. However, these procedures are associated with potential complications. We determined whether the cells present in urine have characteristics of normal bladder cells and investigated their potential uses for urological reconstructive procedures. A total of 55 urine samples were collected from 15 healthy individuals and 8 patients with vesicoureteral reflux. Urine derived cells were isolated, expanded and tested for progenitor and differentiated cell specific markers using flow cytometry, immunofluorescence and Western immunoblotting. The chromosomal stability of cultured urine derived cells was determined by karyotype analysis. Clones were successfully established from primary cultures of urine derived cells. Isolated cells showed 3 phenotypes, including fully differentiated, differentiating and progenitor-like cells. Some urine derived cells stained positive for the surface markers c-Kit, SSEA4, CD105, CD73, CD91, CD133 and CD44. Two to 7 cells per 100 ml urine were multipoint progenitors that could expand extensively in culture. Single progenitor cells had the ability to differentiate into the cell lineages expressing urothelial, smooth muscle, endothelial and interstitial cell markers. The expression of lineage markers was characterized by Western blot and immunofluorescence analysis. Urine derived cells also maintained a normal karyotype after serial culture. A subpopulation of cells isolated from urine had progenitor cell features and the potential to differentiate into several bladder cell lineages. Urine derived cells could serve as an alternative cell source for urinary tract tissue engineering and reconstruction.
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                Author and article information

                Contributors
                adamowicz.jz@gmail.com
                Journal
                Stem Cells Transl Med
                Stem Cells Transl Med
                10.1002/(ISSN)2157-6580
                SCT3
                Stem Cells Translational Medicine
                John Wiley and Sons Inc. (Hoboken )
                2157-6564
                2157-6580
                10 October 2017
                November 2017
                : 6
                : 11 ( doiID: 10.1002/sct3.2017.6.issue-11 )
                : 2033-2043
                Affiliations
                [ 1 ] Chair of Urology, Department of Regenerative Medicine Collegium Medicum, Nicolaus Copernicus University Bydgoszcz Poland
                [ 2 ] Department of Biomedicine University Hospital Basel Switzerland
                Author notes
                [*] [* ]Correspondence: Jan Adamowicz, M.D., Ph.D., Chair of Urology, Department of Regenerative Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, 85‐094, Poland. Telephone: 48525854500; e‐mail: adamowicz.jz@ 123456gmail.com
                Author information
                http://orcid.org/0000-0003-2479-7133
                http://orcid.org/0000-0001-5347-4136
                Article
                SCT312216
                10.1002/sctm.17-0101
                6430044
                29024555
                99fa44f7-2710-4dc2-af29-888a7b1773a8
                © 2017 The Authors stem cells translational medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 18 April 2017
                : 18 July 2017
                Page count
                Figures: 3, Tables: 1, Pages: 11, Words: 10044
                Categories
                Tissue Engineering and Regenerative Medicine
                Not Applicable
                Clinical Application / Translation
                Urogenital Disease
                Urogenital Regeneration
                Wound Healing / Fibrosis
                Tissue Engineering and Regenerative Medicine
                Translational Research Articles and Reviews
                Tissue Engineering and Regenerative Medicine
                Custom metadata
                2.0
                sct312216
                November 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.1 mode:remove_FC converted:22.03.2019

                stem cells,urinary bladder,regeneration,translational medicine,urology

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