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      Regenerative Medicine Strategies for Treating Neurogenic Bladder

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          Abstract

          Neurogenic bladder is a general term encompassing various neurologic dysfunctions of the bladder and the external urethral sphincter. These can be caused by damage or disease. Therapeutic management options can be conservative, minimally invasive, or surgical. The current standard for surgical management is bladder augmentation using intestinal segments. However, because intestinal tissue possesses different functional characteristics than bladder tissue, numerous complications can ensue, including excess mucus production, urinary stone formation, and malignancy. As a result, investigators have sought after alternative solutions. Tissue engineering is a scientific field that uses combinations of cells and biomaterials to encourage regeneration of new, healthy tissue and offers an alternative approach for the replacement of lost or deficient organs, including the bladder. Promising results using tissue-engineered bladder have already been obtained in children with neurogenic bladder caused by myelomeningocele. Human clinical trials, governed by the Food and Drug Administration, are ongoing in the United States in both children and adults to further evaluate the safety and efficacy of this technology. This review will introduce the principles of tissue engineering and discuss how it can be used to treat refractory cases of neurogenic bladder.

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          Most cited references88

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          Adult mesenchymal stem cells for tissue engineering versus regenerative medicine.

          Adult mesenchymal stem cells (MSCs) can be isolated from bone marrow or marrow aspirates and because they are culture-dish adherent, they can be expanded in culture while maintaining their multipotency. The MSCs have been used in preclinical models for tissue engineering of bone, cartilage, muscle, marrow stroma, tendon, fat, and other connective tissues. These tissue-engineered materials show considerable promise for use in rebuilding damaged or diseased mesenchymal tissues. Unanticipated is the realization that the MSCs secrete a large spectrum of bioactive molecules. These molecules are immunosuppressive, especially for T-cells and, thus, allogeneic MSCs can be considered for therapeutic use. In this context, the secreted bioactive molecules provide a regenerative microenvironment for a variety of injured adult tissues to limit the area of damage and to mount a self-regulated regenerative response. This regenerative microenvironment is referred to as trophic activity and, therefore, MSCs appear to be valuable mediators for tissue repair and regeneration. The natural titers of MSCs that are drawn to sites of tissue injury can be augmented by allogeneic MSCs delivered via the bloodstream. Indeed, human clinical trials are now under way to use allogeneic MSCs for treatment of myocardial infarcts, graft-versus-host disease, Crohn's Disease, cartilage and meniscus repair, stroke, and spinal cord injury. This review summarizes the biological basis for the in vivo functioning of MSCs through development and aging.
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            Challenges in tissue engineering.

            Almost 30 years have passed since a term 'tissue engineering' was created to represent a new concept that focuses on regeneration of neotissues from cells with the support of biomaterials and growth factors. This interdisciplinary engineering has attracted much attention as a new therapeutic means that may overcome the drawbacks involved in the current artificial organs and organ transplantation that have been also aiming at replacing lost or severely damaged tissues or organs. However, the tissues regenerated by this tissue engineering and widely applied to patients are still very limited, including skin, bone, cartilage, capillary and periodontal tissues. What are the reasons for such slow advances in clinical applications of tissue engineering? This article gives the brief overview on the current tissue engineering, covering the fundamentals and applications. The fundamentals of tissue engineering involve the cell sources, scaffolds for cell expansion and differentiation and carriers for growth factors. Animal and human trials are the major part of the applications. Based on these results, some critical problems to be resolved for the advances of tissue engineering are addressed from the engineering point of view, emphasizing the close collaboration between medical doctors and biomaterials scientists.
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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

                Journal
                Int Neurourol J
                INJ
                International Neurourology Journal
                Korean Continence Society
                2093-4777
                2093-6931
                September 2011
                30 September 2011
                : 15
                : 3
                : 109-119
                Affiliations
                [1 ]Wake Forest Institute For Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
                [2 ]Joint Institute for Regenerative Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
                [3 ]Department of Urology, Kyungpook National University School of Medicine, Daegu, Korea.
                Author notes
                Corresponding author: James J. Yoo. Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. Tel: +1-336-713-7294 / Fax: +1-336-713-7290 / jyoo@ 123456wakehealth.edu
                Article
                10.5213/inj.2011.15.3.109
                3212584
                22087419
                2ff438de-8788-481e-84c4-e5f0c4fd2942
                Copyright © 2011 Korean Continence Society

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 August 2011
                : 22 September 2011
                Categories
                Review Article

                Neurology
                regenerative medicine,reconstruction,urinary bladder,biomaterials,tissue engineering
                Neurology
                regenerative medicine, reconstruction, urinary bladder, biomaterials, tissue engineering

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