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1
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Kurki A, Paakinaho K, Hannula M, Hyttinen J, Miettinen S, Sartoneva R. Ascorbic Acid 2-Phosphate-Releasing Supercritical Carbon Dioxide-Foamed Poly(L-Lactide-Co-epsilon-Caprolactone) Scaffolds Support Urothelial Cell Growth and Enhance Human Adipose-Derived Stromal Cell Proliferation and Collagen Production. J Tissue Eng Regen Med 2023; 2023:6404468. [PMID: 40226413 PMCID: PMC11919108 DOI: 10.1155/2023/6404468] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 02/15/2023] [Accepted: 02/18/2023] [Indexed: 04/15/2025]
Abstract
Tissue engineering can provide a novel approach for the reconstruction of large urethral defects, which currently lacks optimal repair methods. Cell-seeded scaffolds aim to prevent urethral stricture and scarring, as effective urothelium and stromal tissue regeneration is important in urethral repair. In this study, the aim was to evaluate the effect of the novel porous ascorbic acid 2-phosphate (A2P)-releasing supercritical carbon dioxide-foamed poly(L-lactide-co-ε-caprolactone) (PLCL) scaffolds (scPLCLA2P) on the viability, proliferation, phenotype maintenance, and collagen production of human urothelial cell (hUC) and human adipose-derived stromal cell (hASC) mono- and cocultures. The scPLCLA2P scaffold supported hUC growth and phenotype both in monoculture and in coculture. In monocultures, the proliferation and collagen production of hASCs were significantly increased on the scPLCLA2P compared to scPLCL scaffolds without A2P, on which the hASCs formed nonproliferating cell clusters. Our findings suggest the A2P-releasing scPLCLA2P to be a promising material for urethral tissue engineering.
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Affiliation(s)
- Alma Kurki
- Faculty of Medicine and Health Technology (MET), Tampere University, Tampere, Finland
- Research, Development and Innovation Centre, Tampere University Hospital, Tampere, Finland
| | - Kaarlo Paakinaho
- Faculty of Medicine and Health Technology (MET), Tampere University, Tampere, Finland
| | - Markus Hannula
- Faculty of Medicine and Health Technology (MET), Tampere University, Tampere, Finland
| | - Jari Hyttinen
- Faculty of Medicine and Health Technology (MET), Tampere University, Tampere, Finland
| | - Susanna Miettinen
- Faculty of Medicine and Health Technology (MET), Tampere University, Tampere, Finland
- Research, Development and Innovation Centre, Tampere University Hospital, Tampere, Finland
| | - Reetta Sartoneva
- Faculty of Medicine and Health Technology (MET), Tampere University, Tampere, Finland
- Research, Development and Innovation Centre, Tampere University Hospital, Tampere, Finland
- Department of Obstetrics and Gynaecology, The Hospital District of South Ostrobothnia, Seinäjoki, Finland
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2
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Xuan Z, Zachar V, Pennisi CP. Sources, Selection, and Microenvironmental Preconditioning of Cells for Urethral Tissue Engineering. Int J Mol Sci 2022; 23:14074. [PMID: 36430557 PMCID: PMC9697333 DOI: 10.3390/ijms232214074] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 11/10/2022] [Accepted: 11/12/2022] [Indexed: 11/18/2022] Open
Abstract
Urethral stricture is a common urinary tract disorder in men that can be caused by iatrogenic causes, trauma, inflammation, or infection and often requires reconstructive surgery. The current therapeutic approach for complex urethral strictures usually involves reconstruction with autologous tissue from the oral mucosa. With the goal of overcoming the lack of sufficient autologous tissue and donor site morbidity, research over the past two decades has focused on cell-based tissue-engineered substitutes. While the main focus has been on autologous cells from the penile tissue, bladder, and oral cavity, stem cells from sources such as adipose tissue and urine are competing candidates for future urethral regeneration due to their ease of collection, high proliferative capacity, maturation potential, and paracrine function. This review addresses the sources, advantages, and limitations of cells for tissue engineering in the urethra and discusses recent approaches to improve cell survival, growth, and differentiation by mimicking the mechanical and biophysical properties of the extracellular environment.
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Affiliation(s)
| | | | - Cristian Pablo Pennisi
- Regenerative Medicine Group, Department of Health Science and Technology, Aalborg University, 9220 Aalborg, Denmark
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3
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Reiswich V, Könemann S, Lennartz M, Höflmayer D, Menz A, Chirico V, Hube-Magg C, Fraune C, Bernreuther C, Simon R, Clauditz TS, Sauter G, Hinsch A, Kind S, Jacobsen F, Steurer S, Minner S, Büscheck F, Burandt E, Marx AH, Lebok P, Krech T. Large-scale human tissue analysis identifies Uroplakin 1a as a putative diagnostic marker for urothelial cancer. Pathol Res Pract 2022; 237:154028. [PMID: 35872365 DOI: 10.1016/j.prp.2022.154028] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 07/12/2022] [Accepted: 07/16/2022] [Indexed: 11/27/2022]
Abstract
Uroplakin 1A (Upk1a) protein is relevant for stabilizing and strengthening urothelial cells and helps to prevent them from rupturing during bladder distension. Based on RNA expression data Upk1a is expressed in a limited number of normal tissues and tumors. To comprehensively evaluate the potential diagnostic and prognostic utility of Upk1a immunohistochemistry, a tissue microarray containing 6929 samples from 115 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed. Upk1a positivity was found in 34 (29.6 %) different tumor types including 9 (7.8 %) tumor types with at least one strongly positive case. The highest rates of Upk1a positivity were seen in various subtypes of urothelial neoplasms (42.6-98 %) including Brenner tumors of the ovary (64.9 %) followed by neoplasms of the thyroid (10.4-33.3 %). In urothelial tumors, Upk1a staining predominated at the cell membranes and staining intensity was often moderate to strong. In thyroidal neoplasms the staining was mostly purely cytoplasmic and of low to moderate intensity. Upk1a positivity was also seen in up to 15 % of cases in 25 additional tumor categories but the staining intensity was often cytoplasmic and the intensity was usually judged as weak and only rarely as moderate. Within non-invasive (pTa) tumors, the Upk1a positivity rate decreased from 94 % in pTa G2 (low grade) to 90.1 % in pTa G3 (p = 0.012) and was even lower in muscle-invasive carcinomas (41.5 %; p < 0.0001 vs pTaG3). Within muscle invasive carcinomas, Upk1a expression was unrelated to nodal metastasis (p > 0.05) and patient outcome (p > 0.05). In conclusion, Upk1a immunohistochemistry is a potentially useful and specific diagnostic marker for the distinction of urothelial carcinomas from other neoplasms. However, its sensitivity is less than 50 % in muscle-invasive cancers because Upk1a expression decreases during grade and stage progression.
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Affiliation(s)
- Viktor Reiswich
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Steffi Könemann
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Maximilian Lennartz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Doris Höflmayer
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Anne Menz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Viktoria Chirico
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Claudia Hube-Magg
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christoph Fraune
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christian Bernreuther
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ronald Simon
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
| | - Till S Clauditz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Guido Sauter
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Andrea Hinsch
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Simon Kind
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Frank Jacobsen
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Stefan Steurer
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sarah Minner
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Franziska Büscheck
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Eike Burandt
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Andreas H Marx
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Pathology, Academic Hospital Fuerth, Fuerth, Germany
| | - Patrick Lebok
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany
| | - Till Krech
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany
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4
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Reiswich V, Akdeniz G, Lennartz M, Menz A, Chirico V, Hube-Magg C, Fraune C, Bernreuther C, Simon R, Clauditz TS, Sauter G, Uhlig R, Hinsch A, Kind S, Jacobsen F, Möller K, Steurer S, Minner S, Burandt E, Marx AH, Lebok P, Krech T, Dum D. Large-scale human tissue analysis identifies Uroplakin 1b as a putative diagnostic marker in surgical pathology. Hum Pathol 2022; 126:108-120. [PMID: 35550834 DOI: 10.1016/j.humpath.2022.05.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 05/03/2022] [Indexed: 11/28/2022]
Abstract
Uroplakin 1B (Upk1b) stabilizes epithelial cells lining the bladder lumen to prevent rupturing during bladder distension. Little is known about Upk1b expression in other normal and malignant tissues. To comprehensively evaluate the potential diagnostic and prognostic utility of Upk1b expression analysis, a tissue microarray containing 14,061 samples from 127 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. Upk1b immunostaining was found in 61 (48%) different tumor types including 50 (39%) with at least one moderately positive and 39 tumor types (31%) with at least one strongly positive tumor. Highest positivity rates were found in urothelial neoplasms (58-95%), Brenner tumors of the ovary (92%), epitheloid mesothelioma (87%), serous carcinoma of the ovary (58%) and the endometrium (53%) as well as in squamous cell carcinoma of the head and neck (18-37%), lung (39%) and esophagus (26%). In urothelial carcinoma, low Upk1b expression was linked to high grade and invasive tumor growth (p<0.0001 each) and nodal metastasis (p=0.0006). Our data suggest diagnostic applications of Upk1b immunohistochemistry in panels for the distinction of malignant mesothelioma from adenocarcinoma of the lung, urothelial carcinoma from prostatic adenocarcinoma in the bladder, or pancreatico-biliary and gastro-esophageal from colorectal adenocarcinoma.
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Affiliation(s)
- Viktor Reiswich
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Gonca Akdeniz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Maximilian Lennartz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Anne Menz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Viktoria Chirico
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Claudia Hube-Magg
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christoph Fraune
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christian Bernreuther
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ronald Simon
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
| | - Till S Clauditz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Guido Sauter
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ria Uhlig
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Andrea Hinsch
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Simon Kind
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Frank Jacobsen
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Katharina Möller
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Stefan Steurer
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sarah Minner
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Eike Burandt
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Andreas H Marx
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Pathology, Academic Hospital Fuerth, Fuerth Germany
| | - Patrick Lebok
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Till Krech
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute of Pathology, Clinical Center Osnabrueck, Osnabrueck, Germany
| | - David Dum
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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5
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Kurdi BA, Ababneh NA, Abuharfeil N, Al Demour S, Awidi AS. Use of conditioned media (CM) and xeno-free serum substitute on human adipose-derived stem cells (ADSCs) differentiation into urothelial-like cells. PeerJ 2021; 9:e10890. [PMID: 33850639 PMCID: PMC8019311 DOI: 10.7717/peerj.10890] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 01/12/2021] [Indexed: 01/01/2023] Open
Abstract
Background Congenital abnormalities, cancers as well as injuries can cause irreversible damage to the urinary tract, which eventually requires tissue reconstruction. Smooth muscle cells, endothelial cells, and urothelial cells are the major cell types required for the reconstruction of lower urinary tract. Adult stem cells represent an accessible source of unlimited repertoire of untransformed cells. Aim Fetal bovine serum (FBS) is the most vital supplement in the culture media used for cellular proliferation and differentiation. However, due to the increasing interest in manufacturing xeno-free stem cell-based cellular products, optimizing the composition of the culture media and the serum-type used is of paramount importance. In this study, the effects of FBS and pooled human platelet (pHPL) lysate were assessed on the capacity of human adipose-derived stem cells (ADSCs) to differentiate into urothelial-like cells. Also, we aimed to compare the ability of both conditioned media (CM) and unconditioned urothelial cell media (UCM) to induce urothelial differentiation of ADCS in vitro. Methods ADSCs were isolated from human lipoaspirates and characterized by flow cytometry for their ability to express the most common mesenchymal stem cell (MSCs) markers. The differentiation potential was also assessed by differentiating them into osteogenic and adipogenic cell lineages. To evaluate the capacity of ADSCs to differentiate towards the urothelial-like lineage, cells were cultured with either CM or UCM, supplemented with either 5% pHPL, 2.5% pHPL or 10% FBS. After 14 days of induction, cells were utilized for gene expression and immunofluorescence analysis. Results ADSCs cultured in CM and supplemented with FBS exhibited the highest upregulation levels of the urothelial cell markers; cytokeratin-18 (CK-18), cytokeratin-19 (CK-19), and Uroplakin-2 (UPK-2), with a 6.7, 4.2- and a 2-folds increase in gene expression, respectively. Meanwhile, the use of CM supplemented with either 5% pHPL or 2.5% pHPL, and UCM supplemented with either 5% pHPL or 2.5% pHPL showed low expression levels of CK-18 and CK-19 and no upregulation of UPK-2 level was observed. In contrast, the use of UCM with FBS has increased the levels of CK-18 and CK-19, however to a lesser extent compared to CM. At the cellular level, CK-18 and UPK-2 were only detected in CM/FBS supplemented group. Growth factor analysis revealed an increase in the expression levels of EGF, VEGF and PDGF in all of the differentiated groups. Conclusion Efficient ADSCs urothelial differentiation is dependent on the use of conditioned media. The presence of high concentrations of proliferation-inducing growth factors present in the pHPL reduces the efficiency of ADSCs differentiation towards the urothelial lineage. Additionally, the increase in EGF, VEGF and PDGF during the differentiation implicates them in the mechanism of urothelial cell differentiation.
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Affiliation(s)
- Ban Al- Kurdi
- Cell Therapy Center, University of Jordan, Amman, Jordan.,Department of Hematology and Oncology, Jordan University Hospital, Amman, Jordan
| | | | - Nizar Abuharfeil
- Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid, Jordan
| | - Saddam Al Demour
- Department of Urology, School of medicine, University of Jordan, Amman, Jordan, University of Jordan, Amman, Jordan
| | - Abdalla S Awidi
- Cell Therapy Center, University of Jordan, Amman, Jordan.,Department of Hematology and Oncology, Jordan University Hospital, Amman, Jordan
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6
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Yudintceva NM, Nashchekina YA, Mikhailova NA, Vinogradova TI, Yablonsky PK, Gorelova AA, Muraviov AN, Gorelov AV, Samusenko IA, Nikolaev BP, Yakovleva LY, Shevtsov MA. Urethroplasty with a bilayered poly-D,L-lactide-co-ε-caprolactone scaffold seeded with allogenic mesenchymal stem cells. J Biomed Mater Res B Appl Biomater 2019; 108:1010-1021. [PMID: 31369698 DOI: 10.1002/jbm.b.34453] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 06/28/2019] [Accepted: 07/17/2019] [Indexed: 01/11/2023]
Abstract
Reconstructive surgery for urethral defects employing tissue-engineered scaffolds represents an alternative treatment for urethroplasty. The aim of this study was to compare the therapeutic efficacy of the bilayer poly-D,L-lactide/poly-ε-caprolactone (PL-PC) scaffold seeded with allogenic mesenchymal stem cells (MSCs) for urethra reconstruction in a rabbit model with conventional urethroplasty employing an autologous buccal mucosa graft (BG). The inner layer of the scaffold based on poly-D,L-lactic acid (PL) was seeded with MSCs, while the outer layer, prepared from poly-ε-caprolactone, protected the surrounding tissues from urine. To track the MSCs in vivo, the latter were labeled with superparamagnetic iron oxide nanoparticles. In rabbits, a dorsal penile defect was reconstructed employing a BG or a PL-PC graft seeded with nanoparticle-labeled MSCs. In the 12-week follow-up period, no complications were detected. Subsequent histological analysis demonstrated biointegration of the PL-PC graft with surrounding urethral tissues. Less fibrosis and inflammatory cell infiltration were observed in the experimental group as compared with the BG group. Nanoparticle-labeled MSCs were detected in the urothelium and muscular layer, co-localizing with the urothelium cytokeratin marker AE1/AE3, indicating the possibility of MSC differentiation into neo-urothelium. Our results suggest that a bilayer MSCs-seeded scaffold could be efficiently employed for urethroplasty.
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Affiliation(s)
- Natalia M Yudintceva
- Institute of Cytology of the Russian Academy of Sciences (RAS), St. Petersburg, Russia
| | - Yulia A Nashchekina
- Institute of Cytology of the Russian Academy of Sciences (RAS), St. Petersburg, Russia
| | - Nataliya A Mikhailova
- Institute of Cytology of the Russian Academy of Sciences (RAS), St. Petersburg, Russia
| | - Tatiana I Vinogradova
- Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation, St. Petersburg, Russia
| | - Petr K Yablonsky
- Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation, St. Petersburg, Russia.,Federal State Budgetary Institute, St. Petersburg, Russia
| | - Anna A Gorelova
- Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation, St. Petersburg, Russia.,St. Luca's City Hospital, St. Petersburg, Russia
| | - Alexandr N Muraviov
- Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation, St. Petersburg, Russia.,Private University, Saint-Petersburg Medico-Social Institute, St. Petersburg, Russia
| | - Andrey V Gorelov
- Federal State Budgetary Institute, St. Petersburg, Russia.,Pokrovskaya Municipal Hospital, St. Petersburg, Russia
| | - Igor A Samusenko
- Federal State Budgetary Institute, The Nikiforov Russian Center of Emergency and Radiation Medicine, Ministry of Russian Federation for Civil Defense, Emergencies and Elimination of Consequences of Natural Disasters, St. Petersburg, Russia
| | - Boris P Nikolaev
- Research Institute of Highly Pure Biopreparations, St. Petersburg, Russia
| | | | - Maxim A Shevtsov
- Institute of Cytology of the Russian Academy of Sciences (RAS), St. Petersburg, Russia.,First Pavlov State Medical University of St. Petersburg, St. Petersburg, Russia.,Almazov National Medical Research Centre, Russian Polenov Neurosurgical Institute, St. Petersburg, Russia.,Center for Translational Cancer Research Technische Universität München (TranslaTUM), Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
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7
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Rashidbenam Z, Jasman MH, Hafez P, Tan GH, Goh EH, Fam XI, Ho CCK, Zainuddin ZM, Rajan R, Nor FM, Shuhaili MA, Kosai NR, Imran FH, Ng MH. Overview of Urethral Reconstruction by Tissue Engineering: Current Strategies, Clinical Status and Future Direction. Tissue Eng Regen Med 2019; 16:365-384. [PMID: 31413941 DOI: 10.1007/s13770-019-00193-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 01/03/2019] [Accepted: 01/18/2019] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Urinary tract is subjected to a variety of disorders such as urethral stricture, which often develops as a result of scarring process. Urethral stricture can be treated by urethral dilation and urethrotomy; but in cases of long urethral strictures, substitution urethroplasty with genital skin and buccal mucosa grafts is the only option. However a number of complications such as infection as a result of hair growth in neo-urethra, and stone formation restrict the application of those grafts. Therefore, tissue engineering techniques recently emerged as an alternative approach, aiming to overcome those restrictions. The aim of this review is to provide a comprehensive coverage on the strategies employed and the translational status of urethral tissue engineering over the past years and to propose a combinatory strategy for the future of urethral tissue engineering. METHODs Data collection was based on the key articles published in English language in years between 2006 and 2018 using the searching terms of urethral stricture and tissue engineering on PubMed database. RESULTS Differentiation of mesenchymal stem cells into urothelial and smooth muscle cells to be used for urologic application does not offer any advantage over autologous urothelial and smooth muscle cells. Among studied scaffolds, synthetic scaffolds with proper porosity and mechanical strength is the best option to be used for urethral tissue engineering. CONCLUSION Hypoxia-preconditioned mesenchymal stem cells in combination with autologous cells seeded on a pre-vascularized synthetic and biodegradable scaffold can be said to be the best combinatory strategy in engineering of human urethra.
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Affiliation(s)
- Zahra Rashidbenam
- 1Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, 12th Floor, Clinical Block, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia
| | - Mohd Hafidzul Jasman
- 2Urology Unit, Department of Surgery, Universiti Kebangsaan Malaysia Medical Centre, 8th Floor, Clinical Block, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia
| | - Pezhman Hafez
- 3Faculty of Medicine and Health Science, UCSI University, No. 1 Jalan Puncak Menara Gading, Taman Connaught, 56000 Kuala Lumpur, Malaysia
| | - Guan Hee Tan
- 2Urology Unit, Department of Surgery, Universiti Kebangsaan Malaysia Medical Centre, 8th Floor, Clinical Block, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia
| | - Eng Hong Goh
- 2Urology Unit, Department of Surgery, Universiti Kebangsaan Malaysia Medical Centre, 8th Floor, Clinical Block, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia
| | - Xeng Inn Fam
- 2Urology Unit, Department of Surgery, Universiti Kebangsaan Malaysia Medical Centre, 8th Floor, Clinical Block, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia
| | - Christopher Chee Kong Ho
- 4School of Medicine, Taylor's University, No. 1 Jalan Taylor's, 47500 Subang Jaya, Selangor Darul Ehsan Malaysia
| | - Zulkifli Md Zainuddin
- 2Urology Unit, Department of Surgery, Universiti Kebangsaan Malaysia Medical Centre, 8th Floor, Clinical Block, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia
| | - Reynu Rajan
- 5Minimally Invasive, Upper Gastrointestinal and Bariatric Surgery Unit, Department of Surgery, Universiti Kebangsaan Malaysia Medical Centre, 8th Floor, Clinical Block, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia
| | - Fatimah Mohd Nor
- 6Plastic and Reconstructive Surgery Unit, Department of Surgery, Universiti Kebangsaan Malaysia Medical Centre, Clinical Block, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia
| | - Mohamad Aznan Shuhaili
- 5Minimally Invasive, Upper Gastrointestinal and Bariatric Surgery Unit, Department of Surgery, Universiti Kebangsaan Malaysia Medical Centre, 8th Floor, Clinical Block, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia
| | - Nik Ritza Kosai
- 5Minimally Invasive, Upper Gastrointestinal and Bariatric Surgery Unit, Department of Surgery, Universiti Kebangsaan Malaysia Medical Centre, 8th Floor, Clinical Block, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia
| | - Farrah Hani Imran
- 6Plastic and Reconstructive Surgery Unit, Department of Surgery, Universiti Kebangsaan Malaysia Medical Centre, Clinical Block, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia
| | - Min Hwei Ng
- 1Tissue Engineering Centre, Universiti Kebangsaan Malaysia Medical Centre, 12th Floor, Clinical Block, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia
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8
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Hustler A, Eardley I, Hinley J, Pearson J, Wezel F, Radvanyi F, Baker SC, Southgate J. Differential transcription factor expression by human epithelial cells of buccal and urothelial derivation. Exp Cell Res 2018; 369:284-294. [PMID: 29842880 PMCID: PMC6092173 DOI: 10.1016/j.yexcr.2018.05.031] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Revised: 05/24/2018] [Accepted: 05/25/2018] [Indexed: 12/29/2022]
Abstract
Identification of transcription factors expressed by differentiated cells is informative not only of tissue-specific pathways, but to help identify master regulators for cellular reprogramming. If applied, such an approach could generate healthy autologous tissue-specific cells for clinical use where cells from the homologous tissue are unavailable due to disease. Normal human epithelial cells of buccal and urothelial derivation maintained in identical culture conditions that lacked significant instructive or permissive signaling cues were found to display inherent similarities and differences of phenotype. Investigation of transcription factors implicated in driving urothelial-type differentiation revealed buccal epithelial cells to have minimal or absent expression of PPARG, GATA3 and FOXA1 genes. Retroviral overexpression of protein coding sequences for GATA3 or PPARy1 in buccal epithelial cells resulted in nuclear immunolocalisation of the respective proteins, with both transductions also inducing expression of the urothelial differentiation-associated claudin 3 tight junction protein. PPARG1 overexpression alone entrained expression of nuclear FOXA1 and GATA3 proteins, providing objective evidence of its upstream positioning in a transcription factor network and identifying it as a candidate factor for urothelial-type transdifferentiation or reprogramming.
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Affiliation(s)
- Arianna Hustler
- Jack Birch Unit for Molecular Carcinogenesis, Department of Biology, University of York, York YO10 5DD, United Kingdom
| | - Ian Eardley
- Pyrah Department of Urology, St. James's University Hospital, Leeds LS9 7TF, United Kingdom
| | - Jennifer Hinley
- Jack Birch Unit for Molecular Carcinogenesis, Department of Biology, University of York, York YO10 5DD, United Kingdom
| | - Joanna Pearson
- Jack Birch Unit for Molecular Carcinogenesis, Department of Biology, University of York, York YO10 5DD, United Kingdom
| | - Felix Wezel
- Jack Birch Unit for Molecular Carcinogenesis, Department of Biology, University of York, York YO10 5DD, United Kingdom
| | - Francois Radvanyi
- Oncologie Moléculaire, Institut Curie, Centre de Recherche, 75248 Paris cedex 05, France
| | - Simon C Baker
- Jack Birch Unit for Molecular Carcinogenesis, Department of Biology, University of York, York YO10 5DD, United Kingdom
| | - Jennifer Southgate
- Jack Birch Unit for Molecular Carcinogenesis, Department of Biology, University of York, York YO10 5DD, United Kingdom.
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Smolar J, Horst M, Sulser T, Eberli D. Bladder regeneration through stem cell therapy. Expert Opin Biol Ther 2018; 18:525-544. [DOI: 10.1080/14712598.2018.1439013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Jakub Smolar
- Department of Urology, University Hospital Zurich, Schlieren, Switzerland
| | - Maya Horst
- Department of Urology, University Children’s Hospital Zurich, Zurich, Switzerland
| | - Tulio Sulser
- Department of Urology, University Hospital Zurich, Zurich, Switzerland
| | - Daniel Eberli
- Department of Urology, University Hospital Zurich, Zurich, Switzerland
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10
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Adamowicz J, Pokrywczynska M, Van Breda SV, Kloskowski T, Drewa T. Concise Review: Tissue Engineering of Urinary Bladder; We Still Have a Long Way to Go? Stem Cells Transl Med 2017; 6:2033-2043. [PMID: 29024555 PMCID: PMC6430044 DOI: 10.1002/sctm.17-0101] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Accepted: 07/18/2017] [Indexed: 12/18/2022] Open
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. Stem Cells Translational Medicine 2017;6:2033-2043.
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Affiliation(s)
- Jan Adamowicz
- Chair of Urology, Department of Regenerative Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
| | - Marta Pokrywczynska
- Chair of Urology, Department of Regenerative Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
| | | | - Tomasz Kloskowski
- Chair of Urology, Department of Regenerative Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
| | - Tomasz Drewa
- Chair of Urology, Department of Regenerative Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
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11
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Kuo YC, Rajesh R. Guided differentiation and tissue regeneration of induced pluripotent stem cells using biomaterials. J Taiwan Inst Chem Eng 2017. [DOI: 10.1016/j.jtice.2017.04.043] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Zou Q, Fu Q. Tissue engineering for urinary tract reconstruction and repair: Progress and prospect in China. Asian J Urol 2017; 5:57-68. [PMID: 29736367 PMCID: PMC5934513 DOI: 10.1016/j.ajur.2017.06.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Revised: 03/10/2017] [Accepted: 04/25/2017] [Indexed: 12/11/2022] Open
Abstract
Several urinary tract pathologic conditions, such as strictures, cancer, and obliterations, require reconstructive plastic surgery. Reconstruction of the urinary tract is an intractable task for urologists due to insufficient autologous tissue. Limitations of autologous tissue application prompted urologists to investigate ideal substitutes. Tissue engineering is a new direction in these cases. Advances in tissue engineering over the last 2 decades may offer alternative approaches for the urinary tract reconstruction. The main components of tissue engineering include biomaterials and cells. Biomaterials can be used with or without cultured cells. This paper focuses on cell sources, biomaterials, and existing methods of tissue engineering for urinary tract reconstruction in China. The paper also details challenges and perspectives involved in urinary tract reconstruction.
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Affiliation(s)
- Qingsong Zou
- Department of Urology, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Qiang Fu
- Department of Urology, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China
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13
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Chan YY, Sandlin SK, Kurzrock EA, Osborn SL. The Current Use of Stem Cells in Bladder Tissue Regeneration and Bioengineering. Biomedicines 2017; 5:biomedicines5010004. [PMID: 28536347 PMCID: PMC5423492 DOI: 10.3390/biomedicines5010004] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Revised: 12/23/2016] [Accepted: 12/26/2016] [Indexed: 12/17/2022] Open
Abstract
Many pathological processes including neurogenic bladder and malignancy necessitate bladder reconstruction, which is currently performed using intestinal tissue. The use of intestinal tissue, however, subjects patients to metabolic abnormalities, bladder stones, and other long-term sequelae, raising the need for a source of safe and reliable bladder tissue. Advancements in stem cell biology have catapulted stem cells to the center of many current tissue regeneration and bioengineering strategies. This review presents the recent advancements in the use of stem cells in bladder tissue bioengineering.
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Affiliation(s)
- Yvonne Y Chan
- Department of Urology, Davis School of Medicine, University of California, Sacramento, CA 95817, USA.
| | - Samantha K Sandlin
- Department of Urology, Davis School of Medicine, University of California, Sacramento, CA 95817, USA.
- Stem Cell Program, Institute for Regenerative Cures, University of California, Davis Medical Center, Sacramento, CA 95817, USA.
| | - Eric A Kurzrock
- Department of Urology, Davis School of Medicine, University of California, Sacramento, CA 95817, USA.
- Stem Cell Program, Institute for Regenerative Cures, University of California, Davis Medical Center, Sacramento, CA 95817, USA.
| | - Stephanie L Osborn
- Department of Urology, Davis School of Medicine, University of California, Sacramento, CA 95817, USA.
- Stem Cell Program, Institute for Regenerative Cures, University of California, Davis Medical Center, Sacramento, CA 95817, USA.
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Wang DJ, Li MY, Huang WT, Lu MH, Hu C, Li K, Qiu JG, Gao X. Repair of urethral defects with polylactid acid fibrous membrane seeded with adipose-derived stem cells in a rabbit model. Connect Tissue Res 2015; 56:434-9. [PMID: 25943462 DOI: 10.3109/03008207.2015.1035376] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
AIM The aim of this study is to evaluate the capacity of polylactid acid (PLA) fibrous membrane seeded with allogeneic rabbit adipose tissue-derived stem cells (ADSCs) to repair urethral defects in a rabbit model. MATERIALS AND METHODS Rabbit ADSCs were harvested and phenotypically characterized. Twenty-four New Zealand male rabbits with 5-mm urethral mucosal defects were randomly divided into two groups. They underwent urethroplasty either with PLA fibrous membrane seeded with ADSCs (group A) or blank PLA fibrous membrane (group B). At 4 and 6 weeks after urethroplasty, the urethral grafts were collected and analyzed grossly and histologically. The incidence rate of urethrostenosis was measured. RESULTS The adipose tissue-derived cells in monolayer culture showed a typical morphology of mesenchymal stem cells (MSCs). They were positive for the MSC marker CD44 but negative for lineage markers CD45 and CD105. Six weeks after surgery, the incidence rate of urethrostenosis in group A was significantly lower than that in group B (p < 0.05). In group A, the ADSC-seeded grafts showed a normal urethral architecture with a thickened muscle layer. In contrast, the newly developed urethra in group B demonstrated a fewer number of urothelial layers and scarce or no smooth muscle cells. CONCLUSION The PLA scaffold seeded with ADSCs is effective in urethral regeneration in a rabbit model. ADSCs may represent a promising source of seed cells for urethral tissue engineering.
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Affiliation(s)
- De-juan Wang
- a Department of Urology , The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China
| | - Mao-yin Li
- a Department of Urology , The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China
| | - Wen-tao Huang
- a Department of Urology , The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China
| | - Min-hua Lu
- a Department of Urology , The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China
| | - Cheng Hu
- a Department of Urology , The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China
| | - Ke Li
- a Department of Urology , The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China
| | - Jian-guang Qiu
- a Department of Urology , The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China
| | - Xin Gao
- a Department of Urology , The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China
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Meng L, Liao W, Yang S, Xiong Y, Song C, Liu L. Tissue-engineered tubular substitutions for urinary diversion in a rabbit model. Exp Biol Med (Maywood) 2015; 241:147-56. [PMID: 26286106 DOI: 10.1177/1535370215600101] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Accepted: 07/15/2015] [Indexed: 12/13/2022] Open
Abstract
Clinically, autologous gastrointestinal segments are traditionally used for urinary diversion. However, this procedure often causes many serious complications. Tissue engineering may provide an alternative treatment method in urinary diversion. This research aims to produce tissue-engineered tubular substitutions by using homologous adipose-derived stem cells, smooth muscle cells, and bladder acellular matrix in developing urinary diversion in a rabbit model. Adipose-derived stem cells and smooth muscle cells of rabbit were obtained and cultured in vitro. These cultured adipose-derived stem cells and smooth muscle cells were seeded onto the two sides of the bladder acellular matrix and then incubated for seven days. The cell-seeded matrix was used to build tissue-engineered tubular substitutions, which were then implanted and wrapped into the omentum in vivo for two weeks to promote angiogenesis. In the experimental group, the bladder of 20 rabbits was totally resected, and the above tissue-engineered tubular substitutions were used for urinary diversion. In the control group, bladder acellular matrix tubular substitutions with unseeded cells were implanted into the omentum and were used as urinary diversion on another five rabbits with the same process. The implants were harvested, and histological examination was conducted at 2, 4, 8, and 16 weeks after operation. Intravenous urography assessment was performed at 16 weeks postoperatively. All the rabbits were alive in the experimental group until they were sacrificed. Histological analysis of the construct displayed the presence of multilayer urothelial cells on the luminal side and organized smooth muscle tissue on the other side, and different diameters of neovascularization were clearly identified in the substitutions obtained. No leakage, stricture, or obstructions were noted with intravenous urography assessment. All the animals in the control group died within two weeks, and urine leakage, scar formation, and inflammation were detected through autopsy. This study demonstrates the feasibility of tissue-engineered tubular substitutions constructed using homologous adipose-derived stem cells, smooth muscle cells, and bladder acellular matrix for urinary diversion in a rabbit model.
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Affiliation(s)
- Lingchao Meng
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, People's Republic of China
| | - Wenbiao Liao
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, People's Republic of China
| | - Sixing Yang
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, People's Republic of China
| | - Yunhe Xiong
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, People's Republic of China
| | - Chao Song
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, People's Republic of China
| | - Lingqi Liu
- Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430060, People's Republic of China
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16
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Mousa NA, Abou-Taleb HA, Orabi H. Stem cell applications for pathologies of the urinary bladder. World J Stem Cells 2015; 7:815-822. [PMID: 26131312 PMCID: PMC4478628 DOI: 10.4252/wjsc.v7.i5.815] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2014] [Revised: 02/05/2015] [Accepted: 04/07/2015] [Indexed: 02/06/2023] Open
Abstract
New stem cell based therapies are undergoing intense research and are widely investigated in clinical fields including the urinary system. The urinary bladder performs critical complex functions that rely on its highly coordinated anatomical composition and multiplex of regulatory mechanisms. Bladder pathologies resulting in severe dysfunction are common clinical encounter and often cause significant impairment of patient’s quality of life. Current surgical and medical interventions to correct urinary dysfunction or to replace an absent or defective bladder are sub-optimal and are associated with notable complications. As a result, stem cell based therapies for the urinary bladder are hoped to offer new venues that could make up for limitations of existing therapies. In this article, we review research efforts that describe the use of different types of stem cells in bladder reconstruction, urinary incontinence and retention disorders. In particular, stress urinary incontinence has been a popular target for stem cell based therapies in reported clinical trials. Furthermore, we discuss the relevance of the cancer stem cell hypothesis to the development of bladder cancer. A key subject that should not be overlooked is the safety and quality of stem cell based therapies introduced to human subjects either in a research or a clinical context.
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17
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Andersson KE. Potential of stem cell treatment in detrusor dysfunction. Adv Drug Deliv Rev 2015; 82-83:117-22. [PMID: 25453263 DOI: 10.1016/j.addr.2014.10.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2014] [Revised: 09/03/2014] [Accepted: 10/15/2014] [Indexed: 12/24/2022]
Abstract
The current treatments of bladder dysfunctions, such as bladder overactivity and impaired ability to empty, have limitations, and new treatment alternatives are needed. Stem cell transplantation and tissue engineering have shown promising results in preclinical studies. Stem cells were originally thought to act by differentiating into various cell types, thereby replacing damaged cells and restoring functional deficits. Even if such a mechanism cannot be excluded, the current belief is that a main action is exerted by the stem cells secreting bioactive factors that direct other stem cells to the target organ. In addition, stem cells may exert a number of other effects that can improve bladder dysfunction, since they may have antiapoptotic, antifibrotic, and immunomodulatory properties, and can induce neovascularization. Tissue engineering for bladder replacement, which has had varying success in different animal species, has reached the proof-of-concept state in humans, but recent research suggests that the present approaches may not be optimal. Further studies on new approaches, using animal models with translational predictability, seem necessary for further progress.
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18
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Marędziak M, Marycz K, Lewandowski D, Siudzińska A, Śmieszek A. Static magnetic field enhances synthesis and secretion of membrane-derived microvesicles (MVs) rich in VEGF and BMP-2 in equine adipose-derived stromal cells (EqASCs)-a new approach in veterinary regenerative medicine. In Vitro Cell Dev Biol Anim 2014; 51:230-40. [PMID: 25428200 PMCID: PMC4368852 DOI: 10.1007/s11626-014-9828-0] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2014] [Accepted: 09/23/2014] [Indexed: 12/26/2022]
Abstract
The aim of this work study was to evaluate the cytophysiological activity of equine adipose-derived stem cells (ASCs) cultured under conditions of static magnetic field. Investigated cells were exposed to a static magnetic field (MF) with the intensity of 0.5 T. In order to investigate the effects of magnetic field on stem cell signaling, the localization and density and content of microvesicles (MVs) as well as morphology, ultrastructure, and proliferation rate of equine ASCs were evaluated. Results showed that potential of equine adipose-derived mesenchymal stem cells was accelerated when magnetic field was applied. Resazurin-based assay indicated that the cells cultured in the magnetic field reached the population doubling time earlier and colony-forming potential of equine ASCs was higher when cells were cultured under magnetic field conditions. Morphological and ultrastructural examination of equine ASCs showed that the exposure to magnetic field did not cause any significant changes in cell morphology whereas the polarity of the cells was observed under the magnetic field conditions in ultrastructural examinations. Exposition to MF resulted in a considerable increase in the number of secreted MVs—we have clearly observed the differences between the numbers of MVs shed from the cells cultured under MF in comparison to the control culture and were rich in growth factors. Microvesicles derived from ASCs cultured in the MF condition might be utilized in the stem cell-based treatment of equine musculoskeletal disorders and tendon injuries.
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Affiliation(s)
- Monika Marędziak
- Electron Microscopy Laboratory, University of Environmental and Life Sciences Wroclaw, Kozuchowska 5b, 51-631, Wroclaw, Poland,
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Abstract
Regenerative medicine is an alternative solution for organ transplantation. Stem cells and nanoscaffolds are two essential components in regenerative medicine. Mesenchymal stem cells (MSCs) are considered as primary adult stem cells with high proliferation capacity, wide differentiation potential, and immunosuppression properties which make them unique for regenerative medicine and cell therapy. Scaffolds are engineered nanofibers that provide suitable microenvironment for cell signalling which has a great influence on cell proliferation, differentiation, and biology. Recently, application of scaffolds and MSCs is being utilized in obtaining more homogenous population of MSCs with higher cell proliferation rate and greater differentiation potential, which are crucial factors in regenerative medicine. In this review, the definition, biology, source, characterization, and isolation of MSCs and current report of application of nanofibers in regenerative medicine in different lesions are discussed.
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20
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Generation of bladder urothelium from human pluripotent stem cells under chemically defined serum- and feeder-free system. Int J Mol Sci 2014; 15:7139-57. [PMID: 24776760 PMCID: PMC4057664 DOI: 10.3390/ijms15057139] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2014] [Revised: 03/25/2014] [Accepted: 04/11/2014] [Indexed: 12/11/2022] Open
Abstract
Human stem cells are promising sources for bladder regeneration. Among several possible sources, pluripotent stem cells are the most fascinating because they can differentiate into any cell type, and proliferate limitlessly in vitro. Here, we developed a protocol for differentiation of human pluripotent stem cells (hPSCs) into bladder urothelial cells (BUCs) under a chemically defined culture system. We first differentiated hPSCs into definitive endoderm (DE), and further specified DE cells into BUCs by treating retinoic acid under a keratinocyte-specific serum free medium. hPSC-derived DE cells showed significantly expressed DE-specific genes, but did not express mesodermal or ectodermal genes. After DE cells were specified into BUCs, they notably expressed urothelium-specific genes such as UPIb, UPII, UPIIIa, P63 and CK7. Immunocytochemistry showed that BUCs expressed UPII, CK8/18 and P63 as well as tight junction molecules, E-CADHERIN and ZO-1. Additionally, hPSCs-derived BUCs exhibited low permeability in a FITC-dextran permeability assay, indicating BUCs possessed the functional units of barrier on their surfaces. However, BUCs did not express the marker genes of other endodermal lineage cells (intestine and liver) as well as mesodermal or ectodermal lineage cells. In summary, we sequentially differentiated hPSCs into DE and BUCs in a serum- and feeder-free condition. Our differentiation protocol will be useful for producing cells for bladder regeneration and studying normal and pathological development of the human bladder urothelium in vitro.
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The differentiation of human adipose-derived stem cells towards a urothelium-like phenotype in vitro and the dynamic temporal changes of related cytokines by both paracrine and autocrine signal regulation. PLoS One 2014; 9:e95583. [PMID: 24752317 PMCID: PMC3994076 DOI: 10.1371/journal.pone.0095583] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2013] [Accepted: 03/28/2014] [Indexed: 02/07/2023] Open
Abstract
Purpose To investigate the differentiation ability of human adipose-derived stem cells (ASCs) towards urothelium-like cells in vitro and the dynamic changes of related cytokines and cytokine receptors in the culture medium. Materials and Methods The ASCs were induced using both conditioned media (CM) and the transwell co-culture system with an immortalized urothelium cell line (SV-HUC-1,HUC) for 21 days. Protein and mRNA expression of the mature urothelium specific markers uroplakin-IA (UP-1A) and uroplakin-II (UP-II) were detected by immunofluorescence and quantitative real-time PCR, respectively. Array detection was used to screen 41 cytokines and receptors in the upper medium of urothelium, non-induced ASCs and urothelium-induced ASCs at three time points, early (12 hours), intermediate (7 days) and late (21 days). Results After induction for 7 days, the ASCs grown in both CM and transwell co-culture system expressed uroplakin-IA (13.54±2.00%; 17.28±1.84%) and uroplakin-II (19.49±1.73%; 13.98±1.47%). After induction for 21 days, ASCs grown in co-culture had significantly increased expression of uroplakin-IA (48.03±1.25%; 49.57±2.85%) and uroplakin-II (45.38±2.50%; 46.58±1.95%). In the upper medium of urothelium, 28 cytokines and 8 cytokine receptors had significantly higher expression than the counterpart of non-induced ASCs. After 7 days induction, the expression of 22 cytokines and 8 cytokine receptors was significantly elevated in the upper medium of induced ASCs compared to non-induced ASCs. At the early and intermediate time points, ASCs secreted high levels of relative cytokines and soluble receptors, but their expressions decreased significantly at the late time point. Conclusion The adipose-derived stem cells have the potential to be differentiated into urothelium-like cells in vitro by both CM and transwell co-culture system with mature urothelium. Numerous cytokines and receptors were involved in the differentiation process with dynamic temporal changes by both paracrine and autocrine signal regulation. Further studies should be carried out to determine the detailed mechanism of cytokines and receptors and to enhance the urothelium differentiation efficiency of ASCs.
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miRNA let-7e targeting MMP9 is involved in adipose-derived stem cell differentiation toward epithelia. Cell Death Dis 2014; 5:e1048. [PMID: 24503540 PMCID: PMC3944246 DOI: 10.1038/cddis.2014.2] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2013] [Revised: 10/09/2013] [Accepted: 11/25/2013] [Indexed: 01/29/2023]
Abstract
miRNA let-7e is involved in stem cell differentiation, and metalloproteinases are among its potential target genes. We hypothesized that the inhibitory action of let-7e on regulation of MMP9 expression could represent a crucial mechanism during differentiation of adipose-derived stem cells (ASCs). ASCs were differentiated with all-trans retinoic acid (ATRA) to promote differentiation, and the effect of let-7 silencing during differentiation was tested. Results indicate that ASCs cultured with ATRA differentiated into cells of the epithelial lineage. We found that ASCs cultured with ATRA or transfected with miRNA let-7e expressed epithelial markers such as cytokeratin-18 and early renal organogenesis markers such as Pax2, Wt1, Wnt4 and megalin. Conversely, the specific knockdown of miRNA let-7e in ASCs significantly decreased the expression of these genes, indicating its vital role during the differentiation process. Using luciferase reporter assays, we also showed that MMP9 is a direct target of miRNA let-7e. Thus, our results suggest that miRNA let-7e acts as a matrix metalloproteinase-9 (MMP9) inhibitor and differentiation inducer in ASCs.
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23
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Li H, Xu Y, Xie H, Li C, Song L, Feng C, Zhang Q, Xie M, Wang Y, Lv X. Epithelial-differentiated adipose-derived stem cells seeded bladder acellular matrix grafts for urethral reconstruction: an animal model. Tissue Eng Part A 2014; 20:774-84. [PMID: 24329501 DOI: 10.1089/ten.tea.2013.0122] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
The limited amount of available epithelial tissue is considered a main cause of the high rate of urethral reconstruction failures. The aim of this study was to investigate whether epithelial-differentiated rabbit adipose-derived stem cells (Epith-rASCs) could play a role of epithelium in vivo functionally and be a potential substitute of urothelium. Substitution urethroplasty was performed to repair an anterior urethral defect in male New Zealand rabbits using Epith-rASCs seeded bladder acellular matrix grafts (BAMGs) after 5-bromo-2'-deoxyuridine (BrdU) labeling, based on the in vitro epithelial induction system we previously described. Urethroplasty with cell-free BAMGs and with undifferentiated rASCs (Und-rASCs) seeded BAMGs were performed as controls. After surgery, a notable amelioration of graft contracture and recovery of urethral continuity were observed in the Epith-rASCs/BAMG group by retrograde urethrograms and macroscopic inspection. Immunofluorescence revealed that the BrdU-labeled Epith-rASCs/Und-rASCs colocalized with cytokeratin 13 or myosin. Consistent with the results of western blotting, at early postimplantation stage, the continuous epithelial layer with local multilayered structure was observed in the Epith-rASCs/BAMG group, whereas no significant growth and local monolayer growth profile of epithelial cells were observed in the BAMG and Und-rASCs/BAMG group, respectively. The results showed that Epith-rASCs could serve as a potential substitute of urothelium for urethral tissue engineering and be available to prevent lumen contracture and subsequent complications including recurrent stricture.
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Affiliation(s)
- Hongbin Li
- 1 Department of Urology, Sixth People's Hospital, Jiao Tong University of Shanghai , Shanghai, P.R. China
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Orabi H, Bouhout S, Morissette A, Rousseau A, Chabaud S, Bolduc S. Tissue engineering of urinary bladder and urethra: advances from bench to patients. ScientificWorldJournal 2013; 2013:154564. [PMID: 24453796 PMCID: PMC3886608 DOI: 10.1155/2013/154564] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Accepted: 09/29/2013] [Indexed: 02/05/2023] Open
Abstract
Urinary tract is subjected to many varieties of pathologies since birth including congenital anomalies, trauma, inflammatory lesions, and malignancy. These diseases necessitate the replacement of involved organs and tissues. Shortage of organ donation, problems of immunosuppression, and complications associated with the use of nonnative tissues have urged clinicians and scientists to investigate new therapies, namely, tissue engineering. Tissue engineering follows principles of cell transplantation, materials science, and engineering. Epithelial and muscle cells can be harvested and used for reconstruction of the engineered grafts. These cells must be delivered in a well-organized and differentiated condition because water-seal epithelium and well-oriented muscle layer are needed for proper function of the substitute tissues. Synthetic or natural scaffolds have been used for engineering lower urinary tract. Harnessing autologous cells to produce their own matrix and form scaffolds is a new strategy for engineering bladder and urethra. This self-assembly technique avoids the biosafety and immunological reactions related to the use of biodegradable scaffolds. Autologous equivalents have already been produced for pigs (bladder) and human (urethra and bladder). The purpose of this paper is to present a review for the existing methods of engineering bladder and urethra and to point toward perspectives for their replacement.
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Affiliation(s)
- Hazem Orabi
- Centre LOEX de l'Université Laval, Génie Tissulaire et Régénératrice, LOEX du Centre de Recherche FRQS du Centre de Recherche de CHU de Québec, Axe Médecine Régénératrice, Aile-R Centre Hospitalier Affilié Universitaire de Québec, 1401 18e rue, Québec, QC, Canada G1J 1Z4
| | - Sara Bouhout
- Centre LOEX de l'Université Laval, Génie Tissulaire et Régénératrice, LOEX du Centre de Recherche FRQS du Centre de Recherche de CHU de Québec, Axe Médecine Régénératrice, Aile-R Centre Hospitalier Affilié Universitaire de Québec, 1401 18e rue, Québec, QC, Canada G1J 1Z4
| | - Amélie Morissette
- Centre LOEX de l'Université Laval, Génie Tissulaire et Régénératrice, LOEX du Centre de Recherche FRQS du Centre de Recherche de CHU de Québec, Axe Médecine Régénératrice, Aile-R Centre Hospitalier Affilié Universitaire de Québec, 1401 18e rue, Québec, QC, Canada G1J 1Z4
| | - Alexandre Rousseau
- Centre LOEX de l'Université Laval, Génie Tissulaire et Régénératrice, LOEX du Centre de Recherche FRQS du Centre de Recherche de CHU de Québec, Axe Médecine Régénératrice, Aile-R Centre Hospitalier Affilié Universitaire de Québec, 1401 18e rue, Québec, QC, Canada G1J 1Z4
| | - Stéphane Chabaud
- Centre LOEX de l'Université Laval, Génie Tissulaire et Régénératrice, LOEX du Centre de Recherche FRQS du Centre de Recherche de CHU de Québec, Axe Médecine Régénératrice, Aile-R Centre Hospitalier Affilié Universitaire de Québec, 1401 18e rue, Québec, QC, Canada G1J 1Z4
| | - Stéphane Bolduc
- Centre LOEX de l'Université Laval, Génie Tissulaire et Régénératrice, LOEX du Centre de Recherche FRQS du Centre de Recherche de CHU de Québec, Axe Médecine Régénératrice, Aile-R Centre Hospitalier Affilié Universitaire de Québec, 1401 18e rue, Québec, QC, Canada G1J 1Z4
- Département de Chirurgie, Faculté de Médecine, Université Laval, Québec, QC, Canada G1K 7P4
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Tissue engineering and ureter regeneration: is it possible? Int J Artif Organs 2013; 36:392-405. [PMID: 23645581 DOI: 10.5301/ijao.5000130] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/11/2012] [Indexed: 12/11/2022]
Abstract
Large ureter damages are difficult to reconstruct. Current techniques are complicated, difficult to perform, and often associated with failures. The ureter has never been regenerated thus far. Therefore the use of tissue engineering techniques for ureter reconstruction and regeneration seems to be a promising way to resolve these problems. For proper ureter regeneration the following problems must be considered: the physiological aspects of the tissue, the type and shape of the scaffold, the type of cells, and the specific environment (urine).
This review presents tissue engineering achievements in the field of ureter regeneration focusing on the scaffold, the cells, and ureter healing.
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Zhang M, Peng Y, Zhou Z, Zhou J, Wang Z, Lu M. Differentiation of human adipose-derived stem cells co-cultured with urothelium cell line toward a urothelium-like phenotype in a nude murine model. Urology 2013; 81:465.e15-22. [PMID: 23374843 DOI: 10.1016/j.urology.2012.10.030] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2012] [Revised: 10/01/2012] [Accepted: 10/17/2012] [Indexed: 12/24/2022]
Abstract
OBJECTIVE To investigated the urothelium differentiation potential of adipose-derived stem cells (ASCs) that were coimplanted with the immortalized human bladder urothelium cell line (SV-HUC-1) into the subcutaneous tissue of athymic mice. MATERIALS AND METHODS The ASCs were isolated from the human adipose tissue of patients undergoing liposuction procedures and were expanded in vitro. After labeling with CM-DiI, the ASCs were mixed with SV-HUC-1 and implanted into the subcutaneous tissue of athymic mice for 2 and 4 weeks. The urothelium-specific markers uroplakin-Ia and uroplakin-II were detected by immunofluorescence. The transformation rate of ASCs into the urothelium phenotype was evaluated at each measurement point. RESULTS We found that 25.87% ± 1.38% of ASCs expressed the urothelium-specific marker uroplakin-Ia and 23.60% ± 2.57% of ASCs expressed uroplakin-II 2 weeks after coimplantation with SV-HUC-1 in vivo. After 4 weeks, 70.07% ± 3.84% of ASCs expressed uroplakin-Ia and 65.56% ± 2.94% expressed uroplakin-II. However, no obvious organizational multilayered urothelium structure, such as that of the native bladder mucosa, was found in the subcutaneous tissues of the athymic mice. CONCLUSION The results of our study have demonstrated that ASCs could be differentiated toward the urothelium-like phenotype when they were coimplanted in direct contact with cells of a mature urothelium cell line, and the proportion of differentiated cells increased from 2 to 4 weeks. The differentiation potential of ASCs toward the urothelial cell type suggests that ASCs might have potential to be used in urinary tract repair with a tissue engineering approach in the future.
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Affiliation(s)
- Ming Zhang
- Department of Urology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Abstract
In 2001, researchers at the University of California, Los Angeles, described the isolation of a new population of adult stem cells from liposuctioned adipose tissue. These stem cells, now known as adipose-derived stem cells or ADSCs, have gone on to become one of the most popular adult stem cells populations in the fields of stem cell research and regenerative medicine. As of today, thousands of research and clinical articles have been published using ASCs, describing their possible pluripotency in vitro, their uses in regenerative animal models, and their application to the clinic. This paper outlines the progress made in the ASC field since their initial description in 2001, describing their mesodermal, ectodermal, and endodermal potentials both in vitro and in vivo, their use in mediating inflammation and vascularization during tissue regeneration, and their potential for reprogramming into induced pluripotent cells.
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Drewa T, Joachimiak R, Bajek A, Gagat M, Grzanka A, Bodnar M, Marszalek A, Dębski R, Chłosta P. Hair follicle stem cells can be driven into a urothelial-like phenotype: an experimental study. Int J Urol 2012; 20:537-42. [PMID: 23088347 DOI: 10.1111/j.1442-2042.2012.03202.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2012] [Accepted: 09/19/2012] [Indexed: 12/16/2022]
Abstract
The aim of this study was to show that conditioned medium might induce transdifferentiation of hair follicle stem cells into urothelial-like cells. Several conditioned media and culture conditions (skeletal muscle cell conditioned medium, smooth muscle cell conditioned medium, fibroblast conditioned medium, transforming growth factor-conditioned medium, urothelial cell conditioned medium, and co-culture of hair follicle stem cells and urothelial cells) were used. The hair follicle stem cells phenotype from rat whisker hair follicles was checked by using flow cytometry and immunofluorescence. Cytokeratins 7, 8, 15 and 18 were used as markers. Urothelial cell conditioned medium increased the expression of urothelial markers (cytokeratin 7, cytokeratin 8, cytokeratin 18), whereas it decreased a hair follicle stem cells marker (cytokeratin 15) after 2 weeks of culture. This process depended on the time of cultivation. This medium was able to sustain the epithelial phenotype of the culture. Other media including a co-culture system failed to induce similar changes. Smooth muscle conditioned medium resulted in a loss of cells in culture. Hair follicle stem cells are capable of differentiating into urothelial-like cells in vitro when exposed to a bladder-specific microenvironment.
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Affiliation(s)
- Tomasz Drewa
- Tissue Engineering Department, Nicolaus Copernicus University, Bydgoszcz, Poland.
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Lv X, Zhou G, Liu X, Liu H, Chen J, Liu K, Cao Y. Chondrogenesis by co-culture of adipose-derived stromal cells and chondrocytes in vitro. Connect Tissue Res 2012; 53:492-7. [PMID: 22607649 DOI: 10.3109/03008207.2012.694926] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Adipose-derived stromal cells (ADSCs) could be induced to differentiate into chondrocytes in the presence of cellular factors. In this study, we explored the feasibility of inducing the differentiation of ADSCs into chondrocytes in the presence of chondrocytes. Human ADSCs and porcine auricular chondrocytes were expanded in vitro and then were mixed at the ratio of 7:3. 5.0 × 10(7) mixed cells were seeded onto a polyglycolic acid/polylactic acid scaffold as co-culture group. Chondrocytes and ADSCs with the same cell number were seeded onto the scaffold as positive control group and negative control group. A total of 1.5 × 10(7) chondrocytes were seeded as low-concentration chondrocyte group. After culturing for 8 weeks, gross observation, wet weight, histology, glycosaminoglycan quantification, and collagen II expression were evaluated. Cells in all groups well adhered to the scaffold and could secrete extracellular matrices. In the co-culture group and positive control group, cell-scaffold constructs could maintain the original size and shape during the culture. At the 8th week, cartilage-like tissues were formed, and abundant type II collagen could be detected by immunohistochemistry and reverse transcription-polymerase chain reaction in co-culture and positive control groups. Wet weights and glycosaminoglycan contents of tissues in co-culture group were approximately onefold of those in the negative control group. In the negative control group, constructs shrunk gradually without mature cartilage lacuna formation. In low-concentration chondrocyte group, constructs also shrunk obviously with small amount of cartilage formation. Chondrocytes can provide chondrogenic microenvironment to induce chondrogenic differentiation of ADSCs and thus promote the chondrogenesis of ADSCs in vitro.
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Affiliation(s)
- Xiaojie Lv
- General Hospital of the Second Artillery of PLA, Beijing, PR China.
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Fu Q, Cao YL. Tissue engineering and stem cell application of urethroplasty: from bench to bedside. Urology 2011; 79:246-53. [PMID: 22014966 DOI: 10.1016/j.urology.2011.08.043] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2011] [Revised: 08/13/2011] [Accepted: 08/18/2011] [Indexed: 01/15/2023]
Abstract
OBJECTIVE To review the advances in the basic research and clinical application of tissue engineering and stem cell technology in urethral reconstruction. Urethral defects resulting from congenital malformations, trauma, inflammation, or cancer are a common urologic issue. Traditional urethral reconstruction is associated with various complications. Tissue engineering and stem cell technology hold novel therapeutic promise for urethral reconstruction. METHODS One of us searched the PubMed database (January 1999 to January 2011) using the English search terms "tissue engineering," "stem cells," "urethral reconstruction," and "urethra." A total of 86 reports were retrieved. After the repetitive and irrelevant reports were excluded, 40 were included in the final analysis. The review outlined and evaluated the advances in basic research and clinical application and the current status and prospects of tissue engineering and stem cell technology in urinary reconstruction. RESULTS Two therapeutic strategies are available for urethral reconstruction using tissue engineering: the acellular matrix bioscaffold model and the cell-seeded bioscaffold model. The acellular matrix bioscaffold model has been successfully used in the clinic and the cell-seeded bioscaffold model is making its transition from bench to bedside. CONCLUSION Stem cells can provide the seed cells for urologic tissue engineering, but much basic research is still needed before their clinical use is possible.
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Affiliation(s)
- Qiang Fu
- Department of Urology, Shanghai 6th People's Hospital, Shanghai Jiaotong University, Shanghai, China.
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Lin CS. Advances in stem cell therapy for the lower urinary tract. World J Stem Cells 2010; 2:1-4. [PMID: 21607109 PMCID: PMC3097918 DOI: 10.4252/wjsc.v2.i1.1] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2009] [Revised: 01/06/2010] [Accepted: 01/13/2010] [Indexed: 02/06/2023] Open
Abstract
Lower urinary tract diseases are emotionally and financially burdensome to the individual and society. Current treatments are ineffective or symptomatic. Conversely, stem cells (SCs) are regenerative and may offer long-term solutions. Among the different types of SCs, bone marrow SCs (BMSCs) and skeletal muscle-derived SCs (SkMSCs) have received the most attention in pre-clinical and clinical trial studies concerning the lower urinary tract. In particular, clinical trials with SkMSCs for stress urinary incontinence have demonstrated impressive efficacy. However, both SkMSCs and BMSCs are difficult to obtain in quantity and therefore neither is optimal for the eventual implementation of SC therapy. On the other hand, adipose tissue-derived SCs (ADSCs) can be easily and abundantly obtained from "discarded" adipose tissue. Moreover, in several head-on comparison studies, ADSCs have demonstrated equal or superior therapeutic potential compared to BMSCs. Therefore, across several different medical disciplines, including urology, ADSC research is gaining wide attention. For the regeneration of bladder tissues, possible differentiation of ADSCs into bladder smooth muscle and epithelial cells has been demonstrated. For the treatment of bladder diseases, specifically hyperlipidemia and associated overactive bladder, ADSCs have also demonstrated efficacy. For the treatment of urethral sphincter dysfunction associated with birth trauma and hormonal deficiency, ADSC therapy was also beneficial. Finally, ADSCs were able to restore erectile function in various types of erectile dysfunction (ED), including those associated with diabetes, hyperlipidemia, and nerve injuries. Thus, ADSCs have demonstrated remarkable therapeutic potentials for the lower urinary tract.
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Affiliation(s)
- Ching-Shwun Lin
- Ching-Shwun Lin, Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA 94143-0738, United States
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