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Faegh A, Jahani S, Chinisaz F, Baghaei H, Majidi Zolbin M. Stem cell therapy for bladder regeneration: A comprehensive systematic review. Regen Ther 2025; 28:191-200. [PMID: 39811066 PMCID: PMC11729686 DOI: 10.1016/j.reth.2024.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 11/13/2024] [Accepted: 12/04/2024] [Indexed: 01/16/2025] Open
Abstract
Tissue engineering has been considered a potential choice for urinary system reconstruction. Here, we aim to a broad spectrum of employed stem cells in bladder regeneration by performing a comprehensive systematic review. In January 2024, we searched Scopus, PubMed, and Embase databases for studies that tried bladder regeneration by tissue engineering using stem cells. We excluded non-English studies, review articles, and manuscripts that met the other exclusion criteria. Among 43 included studies, comparative studies demonstrated the similar or superior potentiality of stem cells to regenerate tissues and improve bladder function compared with autologous cells. Furthermore, data suggest an increased use of bio-synthetic scaffolds and their appropriate bio-compatibility with stem cells. The evidence establishes that adipose-derived and bone marrow-derived mesenchymal stem cells are the most frequently used stem cells. And both are suitable for urothelium and smooth muscle formation along with the capability of bone marrow-derived mesenchymal stem cells for lamina propria formation. Additionally, the competency of smooth muscle-derived progenitor cells, urine-derived stem cells, umbilical mesenchymal SCs for smooth muscle and urothelium regeneration, and the capability of hair follicle stem cells for smooth muscle formation are demonstrated. Also, the superiority of endothelial progenitor cells for neo-vascularization and smooth muscle progenitor cells for neuron formation are demonstrated. In addition to adding growth factors to the culturing media, hypoxic conditions and intra-peritoneal incubation are introduced as promoter conditions that can improve histological and physiological components. Available evidence is limited, although it suggests the precious capability of stem cells for bladder regeneration.
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Affiliation(s)
- Ali Faegh
- School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
- Pediatric Urology and Regenerative Medicine Research Center, Gene Cell and Tissue Research Institute Children Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Shima Jahani
- Pediatric Urology and Regenerative Medicine Research Center, Gene Cell and Tissue Research Institute Children Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Chinisaz
- Pediatric Urology and Regenerative Medicine Research Center, Gene Cell and Tissue Research Institute Children Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamoon Baghaei
- Pediatric Urology and Regenerative Medicine Research Center, Gene Cell and Tissue Research Institute Children Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoumeh Majidi Zolbin
- Pediatric Urology and Regenerative Medicine Research Center, Gene Cell and Tissue Research Institute Children Medical Center, Tehran University of Medical Sciences, Tehran, Iran
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Sharma TT, Edassery SL, Rajinikanth N, Karra V, Bury MI, Sharma AK. Proteomic profiling of regenerated urinary bladder tissue in a non-human primate augmentation model. Sci Rep 2024; 14:15757. [PMID: 38977772 PMCID: PMC11231185 DOI: 10.1038/s41598-024-66088-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 06/26/2024] [Indexed: 07/10/2024] Open
Abstract
Urinary bladder dysfunction can be caused by environmental, genetic, and developmental insults. Depending upon insult severity, the bladder may lose its ability to maintain volumetric capacity and intravesical pressure resulting in renal deterioration. Bladder augmentation enterocystoplasty (BAE) is utilized to increase bladder capacity to preserve renal function using autologous bowel tissue as a "patch." To avoid the clinical complications associated with this procedure, we have engineered composite grafts comprised of autologous bone marrow mesenchymal stem cells (MSCs) co-seeded with CD34+ hematopoietic stem/progenitor cells (HSPCs) onto a pliable synthetic scaffold [poly(1,8-octamethylene-citrate-co-octanol)(POCO)] or a biological scaffold (SIS; small intestinal submucosa) to regenerate bladder tissue in our baboon bladder augmentation model. We set out to determine the global protein expression profile of bladder tissue that has undergone regeneration with the aforementioned stem cell seeded scaffolds along with baboons that underwent BAE. Data demonstrate that POCO and SIS grafted animals share high protein homogeneity between native and regenerated tissues while BAE animals displayed heterogeneous protein expression between the tissues following long-term engraftment. We posit that stem cell-seeded scaffolds can recapitulate tissue that is nearly indistinguishable from native tissue at the protein level and may be used in lieu of procedures such as BAE.
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Affiliation(s)
- Tiffany T Sharma
- Division of Pediatric Urology, Ann and Robert H. Lurie Children's Hospital, Chicago, IL, 60611, USA.
- Stanley Manne Children's Research Institute, Simpson Querrey Biomedical Research Center, 303 E. Superior Street, Chicago, IL, 60611, USA.
| | - Seby L Edassery
- Cell and Molecular Physiology Department, Center for Translational Research and Education, Loyola University Chicago, Chicago, IL, 60153, USA
| | - Nachiket Rajinikanth
- Stanley Manne Children's Research Institute, Simpson Querrey Biomedical Research Center, 303 E. Superior Street, Chicago, IL, 60611, USA
| | - Vikram Karra
- Stanley Manne Children's Research Institute, Simpson Querrey Biomedical Research Center, 303 E. Superior Street, Chicago, IL, 60611, USA
| | - Matthew I Bury
- Division of Pediatric Urology, Ann and Robert H. Lurie Children's Hospital, Chicago, IL, 60611, USA
- Stanley Manne Children's Research Institute, Simpson Querrey Biomedical Research Center, 303 E. Superior Street, Chicago, IL, 60611, USA
| | - Arun K Sharma
- Division of Pediatric Urology, Ann and Robert H. Lurie Children's Hospital, Chicago, IL, 60611, USA.
- Stanley Manne Children's Research Institute, Simpson Querrey Biomedical Research Center, 303 E. Superior Street, Chicago, IL, 60611, USA.
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
- Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, 60208, USA.
- Simpson Querrey Institute (SQI), Northwestern University, 303 East Superior Street, Chicago, IL, 60611, USA.
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Rajput SN, Naeem BK, Ali A, Salim A, Khan I. Expansion of human umbilical cord derived mesenchymal stem cells in regenerative medicine. World J Stem Cells 2024; 16:410-433. [PMID: 38690517 PMCID: PMC11056638 DOI: 10.4252/wjsc.v16.i4.410] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 02/01/2024] [Accepted: 03/18/2024] [Indexed: 04/25/2024] Open
Abstract
BACKGROUND Stem cells are undifferentiated cells that possess the potential for self-renewal with the capacity to differentiate into multiple lineages. In humans, their limited numbers pose a challenge in fulfilling the necessary demands for the regeneration and repair of damaged tissues or organs. Studies suggested that mesenchymal stem cells (MSCs), necessary for repair and regeneration via transplantation, require doses ranging from 10 to 400 million cells. Furthermore, the limited expansion of MSCs restricts their therapeutic application. AIM To optimize a novel protocol to achieve qualitative and quantitative expansion of MSCs to reach the targeted number of cells for cellular transplantation and minimize the limitations in stem cell therapy protocols. METHODS Human umbilical cord (hUC) tissue derived MSCs were obtained and re-cultured. These cultured cells were subjected to the following evaluation procedures: Immunophenotyping, immunocytochemical staining, trilineage differentiation, population doubling time and number, gene expression markers for proliferation, cell cycle progression, senescence-associated β-galactosidase assay, human telomerase reverse transcriptase (hTERT) expression, mycoplasma, cytomegalovirus and endotoxin detection. RESULTS Analysis of pluripotent gene markers Oct4, Sox2, and Nanog in recultured hUC-MSC revealed no significant differences. The immunophenotypic markers CD90, CD73, CD105, CD44, vimentin, CD29, Stro-1, and Lin28 were positively expressed by these recultured expanded MSCs, and were found negative for CD34, CD11b, CD19, CD45, and HLA-DR. The recultured hUC-MSC population continued to expand through passage 15. Proliferative gene expression of Pax6, BMP2, and TGFb1 showed no significant variation between recultured hUC-MSC groups. Nevertheless, a significant increase (P < 0.001) in the mitotic phase of the cell cycle was observed in recultured hUC-MSCs. Cellular senescence markers (hTERT expression and β-galactosidase activity) did not show any negative effect on recultured hUC-MSCs. Additionally, quality control assessments consistently confirmed the absence of mycoplasma, cytomegalovirus, and endotoxin contamination. CONCLUSION This study proposes the development of a novel protocol for efficiently expanding stem cell population. This would address the growing demand for larger stem cell doses needed for cellular transplantation and will significantly improve the feasibility of stem cell based therapies.
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Affiliation(s)
- Shafiqa Naeem Rajput
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - Bushra Kiran Naeem
- Surgical Unit 4, Dr. Ruth KM Pfau Civil Hospital, Karachi 74400, Pakistan
| | - Anwar Ali
- Department of Physiology, University of Karachi, Karachi 75270, Pakistan
| | - Asmat Salim
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - Irfan Khan
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Sindh, Pakistan
- Center for Regenerative Medicine and Stem Cells Research, and Department of Ophthalmology and Visual Sciences, The Aga Khan University, Karachi 74800, Sindh, Pakistan.
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Kim J, Bury MI, Kwon K, Yoo JY, Halstead NV, Shin HS, Li S, Won SM, Seo MH, Wu Y, Park DY, Kini M, Kwak JW, Madhvapathy SR, Ciatti JL, Lee JH, Kim S, Ryu H, Yamagishi K, Yoon HJ, Kwak SS, Kim B, Huang Y, Halliday LC, Cheng EY, Ameer GA, Sharma AK, Rogers JA. A wireless, implantable bioelectronic system for monitoring urinary bladder function following surgical recovery. Proc Natl Acad Sci U S A 2024; 121:e2400868121. [PMID: 38547066 PMCID: PMC10998577 DOI: 10.1073/pnas.2400868121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Accepted: 02/25/2024] [Indexed: 04/02/2024] Open
Abstract
Partial cystectomy procedures for urinary bladder-related dysfunction involve long recovery periods, during which urodynamic studies (UDS) intermittently assess lower urinary tract function. However, UDS are not patient-friendly, they exhibit user-to-user variability, and they amount to snapshots in time, limiting the ability to collect continuous, longitudinal data. These procedures also pose the risk of catheter-associated urinary tract infections, which can progress to ascending pyelonephritis due to prolonged lower tract manipulation in high-risk patients. Here, we introduce a fully bladder-implantable platform that allows for continuous, real-time measurements of changes in mechanical strain associated with bladder filling and emptying via wireless telemetry, including a wireless bioresorbable strain gauge validated in a benchtop partial cystectomy model. We demonstrate that this system can reproducibly measure real-time changes in a rodent model up to 30 d postimplantation with minimal foreign body response. Studies in a nonhuman primate partial cystectomy model demonstrate concordance of pressure measurements up to 8 wk compared with traditional UDS. These results suggest that our system can be used as a suitable alternative to UDS for long-term postoperative bladder recovery monitoring.
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Affiliation(s)
- Jihye Kim
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL60208
- School of Advanced Materials Science and Engineering, Sungkyunkwan University, Suwon16419, Republic of Korea
| | - Matthew I. Bury
- Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL60611
- Stanley Manne Children’s Research Institute, Louis A. Simpson and Kimberly K. Querrey Biomedical Research Center, Chicago, IL60611
| | - Kyeongha Kwon
- School of Electrical Engineering, Korea Advanced Institute of Science and Technology, Daejeon34141, Republic of Korea
| | - Jae-Young Yoo
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL60208
- Department of Semiconductor Convergence Engineering, Sungkyunkwan University, Suwon16417, Republic of Korea
| | - Nadia V. Halstead
- Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL60611
| | - Hee-Sup Shin
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL60208
| | - Shupeng Li
- Department of Mechanical Engineering, Northwestern University, Evanston, IL60208
| | - Sang Min Won
- Department of Electrical and Computer Engineering, Sungkyunkwan University, Suwon16419, Republic of Korea
| | - Min-Ho Seo
- Department of Information Convergence Engineering, Pusan National University, Yangsan50612, Republic of Korea
| | - Yunyun Wu
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL60208
| | - Do Yun Park
- School of Electrical Engineering, Korea Advanced Institute of Science and Technology, Daejeon34141, Republic of Korea
| | - Mitali Kini
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL60611
| | - Jean Won Kwak
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL60208
| | - Surabhi R. Madhvapathy
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL60208
| | - Joanna L. Ciatti
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL60208
| | - Jae Hee Lee
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL60208
| | - Suyeon Kim
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL60208
| | - Hanjun Ryu
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL60208
- Department of Advanced Materials Engineering, Chung-Ang University, Anseong17546, Republic of Korea
| | - Kento Yamagishi
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL60208
| | - Hong-Joon Yoon
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL60208
- Department of Electronic Engineering, Gachon University, Seongnam13120, Republic of Korea
| | - Sung Soo Kwak
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL60208
- Bionics Research Center of Biomedical Research Division, Korea Institute of Science and Technology, Seoul02792, Republic of Korea
| | - Bosung Kim
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL60208
| | - Yonggang Huang
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL60208
- Department of Mechanical Engineering, Northwestern University, Evanston, IL60208
| | - Lisa C. Halliday
- Biologic Resources Laboratory, University of Illinois at Chicago, Chicago, IL60612
| | - Earl Y. Cheng
- Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL60611
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL60611
| | - Guillermo A. Ameer
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL60208
- Department of Biomedical Engineering, Northwestern University, Evanston, IL60208
- Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL60208
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL60611
- Chemistry of Life Processes Institute, Northwestern University, Evanston, IL60208
- International Institute for Nanotechnology, Evanston, IL60208
- Simpson Querrey Institute for Bionanotechnology, Evanston, IL60208
| | - Arun K. Sharma
- Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL60611
- Stanley Manne Children’s Research Institute, Louis A. Simpson and Kimberly K. Querrey Biomedical Research Center, Chicago, IL60611
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL60611
- Department of Biomedical Engineering, Northwestern University, Evanston, IL60208
- Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL60208
- Simpson Querrey Institute, Northwestern University, Chicago, IL60611
| | - John A. Rogers
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL60208
- Department of Mechanical Engineering, Northwestern University, Evanston, IL60208
- Department of Biomedical Engineering, Northwestern University, Evanston, IL60208
- Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL60208
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL60611
- Chemistry of Life Processes Institute, Northwestern University, Evanston, IL60208
- International Institute for Nanotechnology, Evanston, IL60208
- Simpson Querrey Institute for Bionanotechnology, Evanston, IL60208
- Department of Material Science and Engineering, Northwestern University, Evanston, IL60208
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL60611
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Setiawan J, Rizal DM, Sofyantoro F, Priyono DS, Septriani NI, Mafiroh WU, Kotani T, Matozaki T, Putri WA. Bibliometric analysis of organoids in regenerative medicine-related research worldwide over two decades (2002-2022). Regen Med 2024; 19:119-133. [PMID: 38449425 DOI: 10.2217/rme-2023-0176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/08/2024] Open
Abstract
Aim: This study aimed to evaluate the trends in organoid culture research within the field of regenerative medicine from 2002 to 2022. Methods: The worldwide distribution of organoid research in regenerative medicine articles indexed in the Scopus database was analyzed. Result: A total of 840 documents were analyzed, averaging 42 publications annually. The USA (n = 296) led in publications, followed by China (n = 127), Japan (n = 91) and the UK (n = 75). Since 2011, research has surged, particularly in China, which emerged as a prominent center. Conclusion: The findings highlight significant growth in organoid research, promising future organ transplantation. Research trends integrate tissue engineering, gene modification and induced pluripotent stem cell technologies, reflecting a move toward personalized medicine.
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Affiliation(s)
- Jajar Setiawan
- Department of Physiology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Dicky Moch Rizal
- Department of Physiology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Fajar Sofyantoro
- Department of Tropical Biology, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Dwi Sendi Priyono
- Department of Tropical Biology, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Nur Indah Septriani
- Department of Tropical Biology, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Wulan Usfi Mafiroh
- Department of Tropical Biology, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Takenori Kotani
- Division of Molecular and Cellular Signaling, Department of Biochemistry & Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takashi Matozaki
- Division of Molecular and Cellular Signaling, Department of Biochemistry & Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan
- Division of Biosignal Regulation, Department of Biochemistry & Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Wahyu Aristyaning Putri
- Department of Tropical Biology, Faculty of Biology, Universitas Gadjah Mada, Yogyakarta, Indonesia
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Bury MI, Fuller NJ, Wang X, Chan YY, Sturm RM, Oh SS, Sofer LA, Arora HC, Sharma TT, Nolan BG, Feng W, Rabizadeh RR, Barac M, Edassery SS, Goedegebuure MM, Wang LW, Ganesh B, Halliday LC, Seniw ME, Edassery SL, Mahmud NB, Hofer MD, McKenna KE, Cheng EY, Ameer GA, Sharma AK. Multipotent bone marrow cell-seeded polymeric composites drive long-term, definitive urinary bladder tissue regeneration. PNAS NEXUS 2024; 3:pgae038. [PMID: 38344009 PMCID: PMC10855019 DOI: 10.1093/pnasnexus/pgae038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 01/16/2024] [Indexed: 03/02/2024]
Abstract
To date, there are no efficacious translational solutions for end-stage urinary bladder dysfunction. Current surgical strategies, including urinary diversion and bladder augmentation enterocystoplasty (BAE), utilize autologous intestinal segments (e.g. ileum) to increase bladder capacity to protect renal function. Considered the standard of care, BAE is fraught with numerous short- and long-term clinical complications. Previous clinical trials employing tissue engineering approaches for bladder tissue regeneration have also been unable to translate bench-top findings into clinical practice. Major obstacles still persist that need to be overcome in order to advance tissue-engineered products into the clinical arena. These include scaffold/bladder incongruencies, the acquisition and utility of appropriate cells for anatomic and physiologic tissue recapitulation, and the choice of an appropriate animal model for testing. In this study, we demonstrate that the elastomeric, bladder biomechanocompatible poly(1,8-octamethylene-citrate-co-octanol) (PRS; synthetic) scaffold coseeded with autologous bone marrow-derived mesenchymal stem cells and CD34+ hematopoietic stem/progenitor cells support robust long-term, functional bladder tissue regeneration within the context of a clinically relevant baboon bladder augmentation model simulating bladder trauma. Partially cystectomized baboons were independently augmented with either autologous ileum or stem-cell-seeded small-intestinal submucosa (SIS; a commercially available biological scaffold) or PRS grafts. Stem-cell synergism promoted functional trilayer bladder tissue regeneration, including whole-graft neurovascularization, in both cell-seeded grafts. However, PRS-augmented animals demonstrated fewer clinical complications and more advantageous tissue characterization metrics compared to ileum and SIS-augmented animals. Two-year study data demonstrate that PRS/stem-cell-seeded grafts drive bladder tissue regeneration and are a suitable alternative to BAE.
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Affiliation(s)
- Matthew I Bury
- Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA
| | - Natalie J Fuller
- Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA
| | - Xinlong Wang
- Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL 60208, USA
| | - Yvonne Y Chan
- Department of Urologic Surgery, University of California at Davis, Davis, CA 95817, USA
| | - Renea M Sturm
- Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
| | - Sang Su Oh
- Biologic Resources Laboratory, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Laurel A Sofer
- Department of Urology, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Hans C Arora
- Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA
| | - Tiffany T Sharma
- Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA
| | - Bonnie G Nolan
- Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA
| | - Wei Feng
- Flow Cytometry Core, Research Resources Center, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Rebecca R Rabizadeh
- Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA
| | - Milica Barac
- Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA
| | - Sonia S Edassery
- Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA
| | - Madeleine M Goedegebuure
- Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL 60208, USA
| | - Larry W Wang
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
| | - Balaji Ganesh
- Flow Cytometry Core, Research Resources Center, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Lisa C Halliday
- Biologic Resources Laboratory, University of Illinois at Chicago, Chicago, IL 60612, USA
| | - Mark E Seniw
- Simpson Querrey Institute, Northwestern University, Chicago, IL 60611, USA
| | - Seby L Edassery
- Center for Translational Research and Education, Loyola University Chicago, Chicago, IL 60153, USA
| | - Nadim B Mahmud
- Division of Hematology/Oncology, Department of Medicine, University of Illinois Cancer Center, Chicago, IL 60612, USA
| | | | - Kevin E McKenna
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
- Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60612, USA
| | - Earl Y Cheng
- Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
- Simpson Querrey Institute, Northwestern University, Chicago, IL 60611, USA
- Stanley Manne Children's Research Institute, Louis A. Simpson and Kimberly K. Querrey Biomedical Research Center, Chicago, IL 60611, USA
- Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL 60208, USA
| | - Guillermo A Ameer
- Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL 60208, USA
- Simpson Querrey Institute, Northwestern University, Chicago, IL 60611, USA
- Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL 60208, USA
- Vascular Surgery, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60612, USA
| | - Arun K Sharma
- Division of Pediatric Urology, Department of Surgery, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA
- Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL 60208, USA
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
- Simpson Querrey Institute, Northwestern University, Chicago, IL 60611, USA
- Stanley Manne Children's Research Institute, Louis A. Simpson and Kimberly K. Querrey Biomedical Research Center, Chicago, IL 60611, USA
- Center for Advanced Regenerative Engineering, Northwestern University, Evanston, IL 60208, USA
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Zhao J, Yang T, Zhou L, Liu J, Mao L, Jia R, Zhao F. Porous gelatin microspheres implanted with adipose mesenchymal stromal cells promote angiogenesis via protein kinase B/endothelial nitric oxide synthase signaling pathway in bladder reconstruction. Cytotherapy 2023; 25:1317-1330. [PMID: 37804283 DOI: 10.1016/j.jcyt.2023.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 08/21/2023] [Accepted: 08/21/2023] [Indexed: 10/09/2023]
Abstract
BACKGROUND AIMS Cell failure and angiogenesis are the key to bladder wall regeneration. Three-dimensional (3D) culture using porous gelatin microspheres (GMs) as a vehicle promotes stem cell proliferation and improves the paracrine capacity of cells. This study aimed to evaluate the therapeutic potential of GMs constructed from adipose-derived mesenchymal stromal cells (ADSCs) (ADSC-GMs) combined with bladder acellular matrix (BAM) in tissue-engineered bladders. METHODS Isolation of ADSCs, flow cytometry, scanning electron microscopy and cell counting kit-8, β-galactosidase and enzyme-linked immunosorbent assays were performed in vitro to compare two-dimensional (2D) and 3D cultures. In the in vivo study, male Sprague-Dawley rats were randomly divided into three groups: the BAM replacement alone (BAM) group, ADSCs grown on BAM in replacement (ADSC) group and ADSC-GMs combined with BAM followed by replacement (ADSC-GM) group. Bladder function assessed by urodynamics after 12 weeks of bladder replacement, and the rats were sacrificed at 4 and 12 weeks for further experiments. RESULTS The in vitro results showed that GM culture promoted ADSC proliferation, inhibited apoptosis and delayed senescence compared with those in the 2D culture. In addition, ADSC-GMs increased the secretion of the angiogenic factors vascular endothelial growth factor, platelet-derived growth factor-BB, and basal fibroblast growth factor. In vivo experiments revealed that ADSC-GMs adhered to the BAM for longer than ADSCs. Moreover, ADSC-GMs significantly promoted the regeneration of bladder vessels and smooth muscle, thereby facilitating the recovery of bladder function. The expression of phosphorylated protein kinase B (AKT) and phosphorylated endothelial nitric oxide synthase (eNOS) was significantly greater in the ADSC-GMs group compared with the BAM and ADSCs groups. CONCLUSIONS ADSC-GMs increased retention of ADSCs on the BAM, thereby promoting the regeneration and functional recovery of the bladder tissue. ADSC-GMs promoted angiogenesis by activating the AKT/eNOS pathway.
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Affiliation(s)
- Jun Zhao
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Tianli Yang
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Liuhua Zhou
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Jingyu Liu
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Liang Mao
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Ruipeng Jia
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
| | - Feng Zhao
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
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8
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Sharma TT, Edassery SL, Rajinikanth N, Karra V, Bury MI, Sharma AK. Proteomic profiling of regenerated urinary bladder tissue with stem cell seeded scaffold composites in a non-human primate bladder augmentation model. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.08.29.554824. [PMID: 37693577 PMCID: PMC10491202 DOI: 10.1101/2023.08.29.554824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/12/2023]
Abstract
Urinary bladder insult can be caused by environmental, genetic, and developmental factors. Depending upon insult severity, the bladder may lose its ability to maintain capacity and intravesical pressures resulting in renal deterioration. Bladder augmentation enterocystoplasty (BAE) is employed to increase bladder capacity to preserve renal function using autologous bowel tissue as a "patch." To avoid the clinical complications associated with this procedure, we have engineered composite grafts comprised of autologous bone marrow mesenchymal stem cells (MSCs) with CD34+ hematopoietic stem/progenitor cells (HSPCs) co-seeded onto a pliable synthetic scaffold [POCO; poly(1,8-octamethylene-citrate-co-octanol)] or a biological scaffold (SIS; small intestinal submucosa) to regenerate bladder tissue in a baboon bladder augmentation model. We set out to determine the protein expression profile of bladder tissue that has undergone regeneration with the aforementioned stem cell seeded scaffolds along with baboons that underwent BAE. Data demonstrate that POCO and SIS grafted animals share high protein homogeneity between native and regenerated tissues while BAE animals displayed heterogenous protein expression between the tissues following long-term engraftment. We posit that stem cell seeded scaffolds can recapitulate tissue that is almost indistinguishable from native tissue at the protein level and may be used in lieu of procedures such as BAE.
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Affiliation(s)
- Tiffany T Sharma
- Division of Pediatric Urology, Ann and Robert H. Lurie Children's Hospital, Chicago, IL 60611, USA
- Stanley Manne Children's Research Institute, Chicago, IL 60611, USA
| | - Seby L Edassery
- Center for Translational Research and Education, Loyola University Chicago, Chicago, IL 60153, USA
| | | | - Vikram Karra
- Stanley Manne Children's Research Institute, Chicago, IL 60611, USA
| | - Matthew I Bury
- Division of Pediatric Urology, Ann and Robert H. Lurie Children's Hospital, Chicago, IL 60611, USA
- Stanley Manne Children's Research Institute, Chicago, IL 60611, USA
| | - Arun K Sharma
- Division of Pediatric Urology, Ann and Robert H. Lurie Children's Hospital, Chicago, IL 60611, USA
- Stanley Manne Children's Research Institute, Chicago, IL 60611, USA
- Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
- Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL 60208, USA
- Simpson Querrey Institute (SQI), Northwestern University, Chicago, IL 60611, USA
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9
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Sueters J, Groenman FA, Bouman MB, Roovers JPW, de Vries R, Smit TH, Huirne JAF. Tissue Engineering Neovagina for Vaginoplasty in Mayer-Rokitansky-Küster-Hauser Syndrome and Gender Dysphoria Patients: A Systematic Review. TISSUE ENGINEERING. PART B, REVIEWS 2023; 29:28-46. [PMID: 35819292 DOI: 10.1089/ten.teb.2022.0067] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Background: Vaginoplasty is a surgical solution to multiple disorders, including Mayer-Rokitansky-Küster-Hauser syndrome and male-to-female gender dysphoria. Using nonvaginal tissues for these reconstructions is associated with many complications, and autologous vaginal tissue may not be sufficient. The potential of tissue engineering for vaginoplasty was studied through a systematic bibliography search. Cell types, biomaterials, and signaling factors were analyzed by investigating advantages, disadvantages, complications, and research quantity. Search Methods: A systematic search was performed in Medline, EMBASE, Web of Science, and Scopus until March 8, 2022. Term combinations for tissue engineering, guided tissue regeneration, regenerative medicine, and tissue scaffold were applied, together with vaginoplasty and neovagina. The snowball method was performed on references and a Google Scholar search on the first 200 hits. Original research articles on human and/or animal subjects that met the inclusion (reconstruction of vaginal tissue and tissue engineering method) and no exclusion criteria (not available as full text; written in foreign language; nonoriginal study article; genital surgery other than neovaginal reconstruction; and vaginal reconstruction with autologous or allogenic tissue without tissue engineering or scaffold) were assessed. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist, the Newcastle-Ottawa Scale, and the Gold Standard Publication Checklist were used to evaluate article quality and bias. Outcomes: A total of 31 out of 1569 articles were included. Data extraction was based on cell origin and type, biomaterial nature and composition, host species, number of hosts and controls, neovaginal size, replacement fraction, and signaling factors. An overview of used tissue engineering methods for neovaginal formation was created, showing high variance of cell types, biomaterials, and signaling factors and the same topics were rarely covered multiple times. Autologous vaginal cells and extracellular matrix-based biomaterials showed preferential properties, and stem cells carry potential. However, quality confirmation of orthotopic cell-seeded acellular vaginal matrix by clinical trials is needed as well as exploration of signaling factors for vaginoplasty. Impact statement General article quality was weak to sufficient due to unreported cofounders and incomplete animal study descriptions. Article quality and heterogenicity made identification of optimal cell types, biomaterials, or signaling factors unreliable. However, trends showed that autologous cells prevent complications and compatibility issues such as healthy cell destruction, whereas stem cells prevent cross talk (interference of signaling pathways by signals from other cell types) and rejection (but need confirmation testing beyond animal trials). Natural (orthotopic) extracellular matrix biomaterials have great preferential properties that encourage future research, and signaling factors for vascularization are important for tissue engineering of full-sized neovagina.
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Affiliation(s)
- Jayson Sueters
- Department of Gynaecology and Amsterdam Reproduction and Development, Amsterdam UMC location VUmc, Amsterdam, The Netherlands
| | - Freek A Groenman
- Department of Obstetrics and Gynecology, Amsterdam Reproduction and Development, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.,Centre of Expertise on Gender Dysphoria, Amsterdam UMC location VUmc, Amsterdam, The Netherlands
| | - Mark-Bram Bouman
- Centre of Expertise on Gender Dysphoria, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.,Department of Plastic, Reconstructive and Hand Surgery, Amsterdam UMC location VUmc, Amsterdam, The Netherlands
| | - Jan Paul W Roovers
- Department of Obstetrics and Gynecology, Amsterdam Reproduction and Development, Amsterdam UMC location VUmc, Amsterdam, The Netherlands
| | - Ralph de Vries
- Medical Library, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Theo H Smit
- Department of Gynaecology and Amsterdam Reproduction and Development, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.,Department of Medical Biology, Amsterdam UMC location AMC, Amsterdam, The Netherlands
| | - Judith A F Huirne
- Department of Gynaecology and Amsterdam Reproduction and Development, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.,Research Institute Reproduction and Development, Amsterdam UMC location AMC, Amsterdam, The Netherlands
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10
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Tissue Engineering and Regenerative Medicine in Pediatric Urology: Urethral and Urinary Bladder Reconstruction. Int J Mol Sci 2022; 23:ijms23126360. [PMID: 35742803 PMCID: PMC9224288 DOI: 10.3390/ijms23126360] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 06/03/2022] [Accepted: 06/05/2022] [Indexed: 11/22/2022] Open
Abstract
In the case of pediatric urology there are several congenital conditions, such as hypospadias and neurogenic bladder, which affect, respectively, the urethra and the urinary bladder. In fact, the gold standard consists of a urethroplasty procedure in the case of urethral malformations and enterocystoplasty in the case of urinary bladder disorders. However, both surgical procedures are associated with severe complications, such as fistulas, urethral strictures, and dehiscence of the repair or recurrence of chordee in the case of urethroplasty, and metabolic disturbances, stone formation, urine leakage, and chronic infections in the case of enterocystoplasty. With the aim of overcoming the issue related to the lack of sufficient and appropriate autologous tissue, increasing attention has been focused on tissue engineering. In this review, both the urethral and the urinary bladder reconstruction strategies were summarized, focusing on pediatric applications and evaluating all the biomaterials tested in both animal models and patients. Particular attention was paid to the capability for tissue regeneration in dependence on the eventual presence of seeded cell and growth factor combinations in several types of scaffolds. Moreover, the main critical features needed for urinary tissue engineering have been highlighted and specifically focused on for pediatric application.
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11
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Porcine Small Intestinal Submucosa (SIS) as a Suitable Scaffold for the Creation of a Tissue-Engineered Urinary Conduit: Decellularization, Biomechanical and Biocompatibility Characterization Using New Approaches. Int J Mol Sci 2022; 23:ijms23052826. [PMID: 35269969 PMCID: PMC8910833 DOI: 10.3390/ijms23052826] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 02/27/2022] [Accepted: 03/01/2022] [Indexed: 02/06/2023] Open
Abstract
Bladder cancer (BC) is among the most common malignancies in the world and a relevant cause of cancer mortality. BC is one of the most frequent causes for bladder removal through radical cystectomy, the gold-standard treatment for localized muscle-invasive and some cases of high-risk, non-muscle-invasive bladder cancer. In order to restore urinary functionality, an autologous intestinal segment has to be used to create a urinary diversion. However, several complications are associated with bowel-tract removal, affecting patients' quality of life. The present study project aims to develop a bio-engineered material to simplify this surgical procedure, avoiding related surgical complications and improving patients' quality of life. The main novelty of such a therapeutic approach is the decellularization of a porcine small intestinal submucosa (SIS) conduit to replace the autologous intestinal segment currently used as urinary diversion after radical cystectomy, while avoiding an immune rejection. Here, we performed a preliminary evaluation of this acellular product by developing a novel decellularization process based on an environmentally friendly, mild detergent, i.e., Tergitol, to replace the recently declared toxic Triton X-100. Treatment efficacy was evaluated through histology, DNA, hydroxyproline and elastin quantification, mechanical and insufflation tests, two-photon microscopy, FTIR analysis, and cytocompatibility tests. The optimized decellularization protocol is effective in removing cells, including DNA content, from the porcine SIS, while preserving the integrity of the extracellular matrix despite an increase in stiffness. An effective sterilization protocol was found, and cytocompatibility of treated SIS was demonstrated from day 1 to day 7, during which human fibroblasts were able to increase in number and strongly organize along tissue fibres. Taken together, this in vitro study suggests that SIS is a suitable candidate for use in urinary diversions in place of autologous intestinal segments, considering the optimal results of decellularization and cell proliferation. Further efforts should be undertaken in order to improve SIS conduit patency and impermeability to realize a future viable substitute.
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12
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Wang X, Shi C, Hou X, Song S, Li C, Cao W, Chen W, Li L. Application of biomaterials and tissue engineering in bladder regeneration. J Biomater Appl 2022; 36:1484-1502. [DOI: 10.1177/08853282211048574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The primary functions of the bladder are storing urine under low and stable pressure and micturition. Various forms of trauma, tumors, and iatrogenic injuries can cause the loss of or reduce bladder function or capacity. If such damage is not treated in time, it will eventually lead to kidney damage and can even be life-threatening in severe cases. The emergence of tissue engineering technology has led to the development of more possibilities for bladder repair and reconstruction, in which the selection of scaffolds is crucial. In recent years, a growing number of tissue-engineered bladder scaffolds have been constructed. Therefore, this paper will discuss the development of tissue-engineered bladder scaffolds and will further analyze the limitations of and challenges encountered in bladder reconstruction.
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Affiliation(s)
- Xiaoya Wang
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
| | - Chunying Shi
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
| | - Xianglin Hou
- Institute of genetics and developmental biology, Chinese Academy of Sciences, Beijing, China
| | - Siqi Song
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
| | - Chenglin Li
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
| | - Wenxuan Cao
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
| | - Wei Chen
- Department of Urology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Ling Li
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
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13
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Hanczar M, Moazen M, Day R. The Significance of Biomechanics and Scaffold Structure for Bladder Tissue Engineering. Int J Mol Sci 2021; 22:ijms222312657. [PMID: 34884464 PMCID: PMC8657955 DOI: 10.3390/ijms222312657] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 10/17/2021] [Accepted: 10/19/2021] [Indexed: 11/23/2022] Open
Abstract
Current approaches for bladder reconstruction surgery are associated with many morbidities. Tissue engineering is considered an ideal approach to create constructs capable of restoring the function of the bladder wall. However, many constructs to date have failed to create a sufficient improvement in bladder capacity due to insufficient neobladder compliance. This review evaluates the biomechanical properties of the bladder wall and how the current reconstructive materials aim to meet this need. To date, limited data from mechanical testing and tissue anisotropy make it challenging to reach a consensus on the native properties of the bladder wall. Many of the materials whose mechanical properties have been quantified do not fall within the range of mechanical properties measured for native bladder wall tissue. Many promising new materials have yet to be mechanically quantified, which makes it difficult to ascertain their likely effectiveness. The impact of scaffold structures and the long-term effect of implanting these materials on their inherent mechanical properties are areas yet to be widely investigated that could provide important insight into the likely longevity of the neobladder construct. In conclusion, there are many opportunities for further investigation into novel materials for bladder reconstruction. Currently, the field would benefit from a consensus on the target values of key mechanical parameters for bladder wall scaffolds.
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Affiliation(s)
- Marta Hanczar
- Applied Biomedical Engineering Group, Centre for Precision Healthcare, UCL Division of Medicine, University College London, London WC1E 6JF, UK;
| | - Mehran Moazen
- UCL Department of Mechanical Engineering, University College London, London WC1E 7JE, UK;
| | - Richard Day
- Applied Biomedical Engineering Group, Centre for Precision Healthcare, UCL Division of Medicine, University College London, London WC1E 6JF, UK;
- Correspondence: ; Tel.: +44-203-108-2183
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14
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Purwaningrum M, Jamilah NS, Purbantoro SD, Sawangmake C, Nantavisai S. Comparative characteristic study from bone marrow-derived mesenchymal stem cells. J Vet Sci 2021; 22:e74. [PMID: 34697921 PMCID: PMC8636658 DOI: 10.4142/jvs.2021.22.e74] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 08/03/2021] [Accepted: 08/05/2021] [Indexed: 11/29/2022] Open
Abstract
Tissue engineering has been extensively investigated and proffered to be a potential platform for novel tissue regeneration. The utilization of mesenchymal stem cells (MSCs) from various sources has been widely explored and compared. In this regard, MSCs derived from bone marrow have been proposed and described as a promising cell resource due to their high yield of isolated cells with colony-forming potential, self-renewal capacity, MSC surface marker expression, and multi-lineage differentiation capacities in vitro. However, there is evidence for bone marrow MSCs (BM-MSCs) both in vitro and in vivo from different species presenting identical and distinct potential stemness characteristics. In this review, the fundamental knowledge of the growth kinetics and stemness properties of BM-MSCs in different animal species and humans are compared and summarized. Finally, to provide a full perspective, this review will procure results of current information studies focusing on the use of BM-MSCs in clinical practice.
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Affiliation(s)
- Medania Purwaningrum
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Veterinary Pharmacology and Stem Cell Research Laboratory, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.,Department of Biochemistry, Faculty of Veterinary Medicine, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
| | - Nabila Syarifah Jamilah
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Veterinary Pharmacology and Stem Cell Research Laboratory, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand
| | - Steven Dwi Purbantoro
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Veterinary Pharmacology and Stem Cell Research Laboratory, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand
| | - Chenphop Sawangmake
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Veterinary Pharmacology and Stem Cell Research Laboratory, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.,Veterinary Stem Cell and Bioengineering Research Unit, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.,Department of Pharmacology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand
| | - Sirirat Nantavisai
- Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Veterinary Pharmacology and Stem Cell Research Laboratory, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.,Veterinary Stem Cell and Bioengineering Research Unit, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.
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15
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Shih KW, Chen WC, Chang CH, Tai TE, Wu JC, Huang AC, Liu MC. Non-Muscular Invasive Bladder Cancer: Re-envisioning Therapeutic Journey from Traditional to Regenerative Interventions. Aging Dis 2021; 12:868-885. [PMID: 34094648 PMCID: PMC8139208 DOI: 10.14336/ad.2020.1109] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Accepted: 11/09/2020] [Indexed: 01/01/2023] Open
Abstract
Non-muscular invasive bladder cancer (NMIBC) is one of the most common cancer and major cause of economical and health burden in developed countries. Progression of NMIBC has been characterized as low-grade (Ta) and high grade (carcinoma in situ and T1). The current surgical intervention for NMIBC includes transurethral resection of bladder tumor; however, its recurrence still remains a challenge. The BCG-based immunotherapy is much effective against low-grade NMIBC. BCG increases the influx of T cells at bladder cancer site and inhibits proliferation of bladder cancer cells. The chemotherapy is another traditional approach to address NMIBC by supplementing BCG. Notwithstanding, these current therapeutic measures possess limited efficacy in controlling NMIBC, and do not provide comprehensive long-term relief. Hence, biomaterials and scaffolds seem an effective medium to deliver therapeutic agents for restructuring bladder post-treatment. The regenerative therapies such as stem cells and PRP have also been explored for possible solution to NMIBC. Based on above-mentioned approaches, we have comprehensively analyzed therapeutic journey from traditional to regenerative interventions for the treatment of NMIBC.
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Affiliation(s)
- Kuan-Wei Shih
- 1Department of Urology, Taipei Medical University Hospital, Taipei 11031, Taiwan
| | - Wei-Chieh Chen
- 1Department of Urology, Taipei Medical University Hospital, Taipei 11031, Taiwan.,2Graduate Institute of Clinical Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.,3TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei 11031, Taiwan
| | - Ching-Hsin Chang
- 1Department of Urology, Taipei Medical University Hospital, Taipei 11031, Taiwan.,3TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei 11031, Taiwan.,4Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 11031, Taiwan
| | - Ting-En Tai
- 1Department of Urology, Taipei Medical University Hospital, Taipei 11031, Taiwan
| | - Jeng-Cheng Wu
- 1Department of Urology, Taipei Medical University Hospital, Taipei 11031, Taiwan.,3TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei 11031, Taiwan.,5Department of Education, Taipei Medical University Hospital, Taipei 11031, Taiwan.,6Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
| | - Andy C Huang
- 8Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei,11221, Taiwan.,9Department of Urology, Department of Surgery, Taipei City Hospital Ren-Ai Branch, Taipei 10629, Taiwan
| | - Ming-Che Liu
- 1Department of Urology, Taipei Medical University Hospital, Taipei 11031, Taiwan.,2Graduate Institute of Clinical Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.,3TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei 11031, Taiwan.,7Clinical Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan.,10School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
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16
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Yang T, Zhao F, Zhou L, Liu J, Xu L, Dou Q, Xu Z, Jia R. Therapeutic potential of adipose-derived mesenchymal stem cell exosomes in tissue-engineered bladders. J Tissue Eng 2021; 12:20417314211001545. [PMID: 33868627 PMCID: PMC8020766 DOI: 10.1177/20417314211001545] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 02/17/2021] [Indexed: 01/08/2023] Open
Abstract
Mesenchymal stem cells (MSCs) are a therapeutic tool for tissue engineering. However, many studies have recently shown that the therapeutic effects of MSCs are mediated by paracrine signaling and their secretory factors rather than their multidirectional differentiation ability. Exosomes isolated from the conditioned medium of MSCs are considered the main intercellular communication medium between MSCs and their target cells. Exosomes have been utilized in a novel cell-free therapy strategy that has attracted much attention. In this study, we evaluated the effects of a new cell-free tissue-engineered bladder (bladder acellular matrix combined with adipose-derived mesenchymal stem cell exosomes (AMEs)) in vivo and in vitro to prove that AMEs promoted tissue regeneration and functional recovery in a rat bladder replacement model.
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Affiliation(s)
- Tianli Yang
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Feng Zhao
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Liuhua Zhou
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Jingyu Liu
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Luwei Xu
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Quanliang Dou
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Zheng Xu
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Ruipeng Jia
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
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17
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Robb KP, Juignet L, Morissette Martin P, Walker JT, Brooks CR, Barreira C, Dekaban GA, Flynn LE. Adipose Stromal Cells Enhance Decellularized Adipose Tissue Remodeling Through Multimodal Mechanisms. Tissue Eng Part A 2020; 27:618-630. [PMID: 32873224 DOI: 10.1089/ten.tea.2020.0180] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Decellularized adipose tissue (DAT) scaffolds represent a promising cell-instructive platform for soft tissue engineering. While recent work has highlighted that mesenchymal stromal cells, including adipose-derived stromal cells (ASCs), can be combined with decellularized scaffolds to augment tissue regeneration, the mechanisms involved require further study. The objective of this work was to probe the roles of syngeneic donor ASCs and host-derived macrophages in tissue remodeling of DAT scaffolds within an immunocompetent mouse model. Dual transgenic reporter mouse strains were employed to track and characterize the donor ASCs and host macrophages within the DAT implants. More specifically, ASCs isolated from dsRed mice were seeded on DAT scaffolds, and the seeded and unseeded control scaffolds were implanted subcutaneously into MacGreen transgenic mice for up to 8 weeks. ASC seeding was shown to augment cell infiltration into the DAT implants at 8 weeks, and this was linked to significantly enhanced angiogenesis relative to the unseeded controls. Immunohistochemical staining demonstrated long-term retention of the syngeneic donor ASCs over the duration of the 8-week study, providing evidence that the DAT scaffolds are a cell-supportive delivery platform. Notably, newly formed adipocytes within the DAT implants were not dsRed+, indicating that the donor ASCs supported fat formation through indirect mechanisms. Immunohistochemical tracking of host macrophages through costaining for enhanced green fluorescent protein with the macrophage marker Iba1 revealed that ASC seeding significantly increased the number of infiltrating macrophages within the DAT implants at 3 weeks, while the fraction of macrophages relative to the total cellular infiltrate was similar between the groups at 1, 3, and 8 weeks. Consistent with the tissue remodeling response that was observed, western blotting demonstrated that there was significantly augmented expression of CD163 and CD206, markers of constructive M2-like macrophages, within the ASC-seeded DAT implants. Overall, our results demonstrate that exogenous ASCs enhance tissue regeneration within DAT scaffolds indirectly through multimodal mechanisms that include host cell recruitment and immunomodulation. These data provide further evidence to support the use of decellularized scaffolds as a delivery platform for ASCs in tissue engineering.
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Affiliation(s)
- Kevin P Robb
- School of Biomedical Engineering, University of Western Ontario, London, Canada
| | - Laura Juignet
- Department of Anatomy and Cell Biology and Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada
| | - Pascal Morissette Martin
- Department of Anatomy and Cell Biology and Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada
| | - John T Walker
- Department of Anatomy and Cell Biology and Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada
| | - Courtney R Brooks
- Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada
| | - Christy Barreira
- Molecular Medicine Research Laboratories, Robarts Research Institute, University of Western Ontario, London, Canada
| | - Gregory A Dekaban
- Molecular Medicine Research Laboratories, Robarts Research Institute, University of Western Ontario, London, Canada.,Department of Microbiology & Immunology and University of Western Ontario, London, Canada
| | - Lauren E Flynn
- School of Biomedical Engineering, University of Western Ontario, London, Canada.,Department of Anatomy and Cell Biology and Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada.,Department of Chemical and Biochemical Engineering, University of Western Ontario, London, Canada.,Bone and Joint Institute, University of Western Ontario, London, Canada
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18
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Abdal Dayem A, Kim K, Lee SB, Kim A, Cho SG. Application of Adult and Pluripotent Stem Cells in Interstitial Cystitis/Bladder Pain Syndrome Therapy: Methods and Perspectives. J Clin Med 2020; 9:jcm9030766. [PMID: 32178321 PMCID: PMC7141265 DOI: 10.3390/jcm9030766] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 03/04/2020] [Accepted: 03/09/2020] [Indexed: 12/11/2022] Open
Abstract
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a multifactorial, chronic disease without definite etiology characterized by bladder-related pelvic pain. IC/BPS is associated with pain that negatively affects the quality of life. There are various therapeutic approaches against IC/BPS. However, no efficient therapeutic agent against IC/BPS has been discovered yet. Urothelium dysfunction is one of the key factors of IC/BPS-related pathogenicity. Stem cells, including adult stem cells (ASCs) and pluripotent stem cells (PSCs), such as embryonic stem cells (ESCs) and induced PSCs (iPSCs), possess the abilities of self-renewal, proliferation, and differentiation into various cell types, including urothelial and other bladder cells. Therefore, stem cells are considered robust candidates for bladder regeneration. This review provides a brief overview of the etiology, pathophysiology, diagnosis, and treatment of IC/BPS as well as a summary of ASCs and PSCs. The potential of ASCs and PSCs in bladder regeneration via differentiation into bladder cells or direct transplantation into the bladder and the possible applications in IC/BPS therapy are described in detail. A better understanding of current studies on stem cells and bladder regeneration will allow further improvement in the approaches of stem cell applications for highly efficient IC/BPS therapy.
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Affiliation(s)
- Ahmed Abdal Dayem
- Department of Stem Cell & Regenerative Biotechnology and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea; (A.A.D.); (K.K.); (S.B.L.)
| | - Kyeongseok Kim
- Department of Stem Cell & Regenerative Biotechnology and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea; (A.A.D.); (K.K.); (S.B.L.)
| | - Soo Bin Lee
- Department of Stem Cell & Regenerative Biotechnology and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea; (A.A.D.); (K.K.); (S.B.L.)
| | - Aram Kim
- Department of Urology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05029, Korea
- Correspondence: (A.K.); (S.-G.C.); Tel.: +82-2-2030-7675 (A.K.); +82-2-450-4207 (S.-G.C.); Fax: +82-2-2030-7748 (A.K.); +82-2-450-4207 (S.-G.C.)
| | - Ssang-Goo Cho
- Department of Stem Cell & Regenerative Biotechnology and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea; (A.A.D.); (K.K.); (S.B.L.)
- Correspondence: (A.K.); (S.-G.C.); Tel.: +82-2-2030-7675 (A.K.); +82-2-450-4207 (S.-G.C.); Fax: +82-2-2030-7748 (A.K.); +82-2-450-4207 (S.-G.C.)
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19
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Arakelian L, Caille C, Faivre L, Corté L, Bruneval P, Shamdani S, Flageollet C, Albanese P, Domet T, Jarraya M, Setterblad N, Kellouche S, Larghero J, Cattan P, Vanneaux V. A clinical-grade acellular matrix for esophageal replacement. J Tissue Eng Regen Med 2019; 13:2191-2203. [PMID: 31670903 DOI: 10.1002/term.2983] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 09/24/2019] [Accepted: 10/03/2019] [Indexed: 11/09/2022]
Abstract
In pathologies of the esophagus such as esophageal atresia, cancers, and caustic injuries, methods for full thickness esophageal replacement require the sacrifice of healthy intra-abdominal organs such as the stomach and the colon and are associated with high morbidity, mortality, and poor functional results. To overcome these problems, tissue engineering methods are developed to create a substitute with scaffolds and cells. The aim of this study was to develop a simple and safe decellularization process in order to obtain a clinical grade esophageal extracellular matrix. Following the decontamination step, porcine esophagi were decellularized in a bioreactor with sodium dodecyl sulfate and ethylenediaminetetraacetic acid for 3 days and were rinsed with deionized water. DNA was eliminated by a 3-hr DNase treatment. To remove any residual detergent, the matrix was then incubated with an absorbing resin. The resulting porcine esophageal matrix was characterized by the assessment of the efficiency of the decellularization process (DNA quantification), evaluation of sterility and absence of cytotoxicity, and its composition and biomechanical properties, as well as the possibility to be reseeded with mesenchymal stem cells. Complete decellularization with the preservation of the general structure, composition, and biomechanical properties of the native esophageal matrix was obtained. Sterility was maintained throughout the process, and the matrix showed no cytotoxicity. The resulting matrix met clinical grade criteria and was successfully reseeded with mesenchymal stem cells..
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Affiliation(s)
- Lousineh Arakelian
- Unité de Thérapie Cellulaire, Hôpital Saint-Louis, AP-HP, Paris, France.,Institut de Recherche Saint Louis, INSERM, CIC-BT1427 and UMR-U976, Hôpital St-Louis, Paris, France
| | - Clémentine Caille
- Unité de Thérapie Cellulaire, Hôpital Saint-Louis, AP-HP, Paris, France.,Institut de Recherche Saint Louis, INSERM, CIC-BT1427 and UMR-U976, Hôpital St-Louis, Paris, France
| | - Lionel Faivre
- Unité de Thérapie Cellulaire, Hôpital Saint-Louis, AP-HP, Paris, France.,Institut de Recherche Saint Louis, INSERM, CIC-BT1427 and UMR-U976, Hôpital St-Louis, Paris, France
| | - Laurent Corté
- MAT-Centre des Matériaux, MINES ParisTech, PSL Research University, CNRS UMR 7633, France.,Laboratoire Matière Molle et Chimie, ESPCI Paris, PSL Research University, CNRS UMR 7167, Paris, France
| | - Patrick Bruneval
- Department of Pathology, Georges Pompidou European Hospital, AP-HP, Paris, France
| | - Sara Shamdani
- Laboratoire CRRET, Université Paris Est Créteil, Université Paris Est, EA 4397 ERL CNRS 9215, Créteil, France
| | - Camille Flageollet
- Laboratoire CRRET, Université Paris Est Créteil, Université Paris Est, EA 4397 ERL CNRS 9215, Créteil, France
| | - Patricia Albanese
- Laboratoire CRRET, Université Paris Est Créteil, Université Paris Est, EA 4397 ERL CNRS 9215, Créteil, France
| | - Thomas Domet
- Unité de Thérapie Cellulaire, Hôpital Saint-Louis, AP-HP, Paris, France.,Institut de Recherche Saint Louis, INSERM, CIC-BT1427 and UMR-U976, Hôpital St-Louis, Paris, France
| | - Mohamed Jarraya
- Banque des Tissus Humains, Hôpital St-Louis, AP-HP, Paris, France
| | - Niclas Setterblad
- Technological Core facility of the Hematology Institute, Université Paris-Diderot and Inserm, Hôpital Saint-Louis, Paris, France
| | - Sabrina Kellouche
- Equipe de Recherche sur les Relations Matrice Extracellulaire-Cellules, ERRMECe (EA1391), Institut des Matériaux, I-MAT (FD4122), University of Cergy-Pontoise, MIR, France
| | - Jérôme Larghero
- Unité de Thérapie Cellulaire, Hôpital Saint-Louis, AP-HP, Paris, France.,Institut de Recherche Saint Louis, INSERM, CIC-BT1427 and UMR-U976, Hôpital St-Louis, Paris, France
| | - Pierre Cattan
- Institut de Recherche Saint Louis, INSERM, CIC-BT1427 and UMR-U976, Hôpital St-Louis, Paris, France.,Department of Digestive Surgery, St-Louis Hospital-Paris 7 University, Paris, France
| | - Valérie Vanneaux
- Unité de Thérapie Cellulaire, Hôpital Saint-Louis, AP-HP, Paris, France.,Institut de Recherche Saint Louis, INSERM, CIC-BT1427 and UMR-U976, Hôpital St-Louis, Paris, France
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20
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Ghahremani-Nasab M, Ghanbari E, Jahanbani Y, Mehdizadeh A, Yousefi M. Premature ovarian failure and tissue engineering. J Cell Physiol 2019; 235:4217-4226. [PMID: 31663142 DOI: 10.1002/jcp.29376] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 09/30/2019] [Indexed: 12/30/2022]
Abstract
Premature ovarian failure (POF) usually happens former to the age of 40 and affects the female physiological state premenopausal period. In this condition, ovaries stop working long before the expected menopausal time. Of diagnostic symptoms of the disease, one can mention amenorrhea and hypoestrogenism. The cause of POF in most cases is idiopathic; however, cancer therapy may also cause POF. Commonly utilized therapies such as hormone therapy, in-vitro activation, and regenerative medicine are the most well-known treatments for POF. Hence, these therapies may be associated with some complications. The aim of the present study is to discuss the beneficial effects of tissue engineering for fertility rehabilitation in patients with POF as a newly emerging therapy.
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Affiliation(s)
- Maryam Ghahremani-Nasab
- Department of Tissue Engineering, Tabriz University of Medical Sciences, Tabriz, Iran.,Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Elham Ghanbari
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Yalda Jahanbani
- School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Mehdizadeh
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Comprehensive Health Lab, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Yousefi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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21
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Sharma S, Gupta DK. Tissue Engineering and Stem Cell Therapy in Pediatric Urology. J Indian Assoc Pediatr Surg 2019; 24:237-246. [PMID: 31571753 PMCID: PMC6752070 DOI: 10.4103/jiaps.jiaps_77_18] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
The rapidly expanding field of tissue engineering along with stem cell therapy has a promising future in pediatric urological conditions. The initial struggle seemed difficult in renal regeneration but a functional biounit has been developed. Urine excretion has been demonstrated successfully from stem cell-generated embryonic kidneys. Three-dimensional (3D) stem cell-derived organoids are the new paradigm in research. Techniques to regenerate bladder tissue have reached the clinic, and the urethra is close behind. 3D bioprinted urethras would soon be available. Artificial germ cells produced from mouse pluripotent stem cells have been shown to give rise to live progeny. Myoblast and fibroblast therapy has been safely and effectively used for urinary incontinence. Stress urinary incontinence has been clinically treated with muscle-derived stem cells. Skeletal muscle-derived stem cells have been shown to get converted into smooth muscle cells when implanted into the corpora cavernosa in animal models. This review encompasses the various experimental and clinical developments in this field that can benefit pediatric urological conditions with the contemporary developments in the field.
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Affiliation(s)
- Shilpa Sharma
- Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Devendra K. Gupta
- Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, India
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22
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Pokrywczynska M, Rasmus M, Jundzill A, Balcerczyk D, Adamowicz J, Warda K, Buchholz L, Drewa T. Mesenchymal stromal cells modulate the molecular pattern of healing process in tissue-engineered urinary bladder: the microarray data. Stem Cell Res Ther 2019; 10:176. [PMID: 31196214 PMCID: PMC6567623 DOI: 10.1186/s13287-019-1266-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Revised: 05/13/2019] [Accepted: 05/14/2019] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Molecular mechanisms underlying the regenerative process induced by stem cells in tissue-engineered urinary bladder are poorly explained. The study was performed to explore the pathways associated with regeneration process in the urinary bladder reconstructed with adipose tissue-derived mesenchymal stromal cells (ASCs). METHODS Rat urinary bladders were reconstructed with bladder acellular matrix (BAM) (n = 52) or BAM seeded with adipose tissue-derived mesenchymal stromal cells (ASCs) (n = 52). The process of bladder healing was analyzed at 7, 30, 90, and 180 days postoperatively using macroscopic histologic and molecular techniques. Gene expression was analyzed by microarrays and confirmed by real-time PCR. RESULTS Numerous differentially expressed genes (DEGs) were identified between the bladders augmented with BAM seeded with ASCs or BAM only. Pathway analysis of DEGs allows to discover numerous pathways among them Hedgehog, TGF-β, Jak-STAT, PI3-Akt, and Hippo modulated by ASCs during the healing process of tissue-engineered urinary bladder. Real-time PCR analysis confirmed upregulation of genes involved in the Hedgehog signaling pathway including Shh, Gli1, Smo, Bmp2, Bmp4, Wnt2, Wnt2b, Wnt4, Wnt5a, and Wnt10 in urinary bladders reconstructed with ASC-seeded grafts. CONCLUSION The study provided the unequivocal evidence that ASCs change the molecular pattern of healing in tissue-engineered urinary bladder and indicated which signaling pathways triggered by ASCs can be associated with the regenerative process. These pathways can be used as targets in the future studies on induced urinary bladder regeneration. Of particular interest is the Hedgehog signaling pathway that has been upregulated by ASCs during healing of tissue-engineered urinary bladder.
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Affiliation(s)
- Marta Pokrywczynska
- Department of Regenerative Medicine, Cell and Tissue Bank, Chair of Urology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, 85-094, Marii Sklodowskiej Curie 9 Street, 85-094, Bydgoszcz, Poland.
| | - Marta Rasmus
- Department of Regenerative Medicine, Cell and Tissue Bank, Chair of Urology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, 85-094, Marii Sklodowskiej Curie 9 Street, 85-094, Bydgoszcz, Poland
| | - Arkadiusz Jundzill
- Department of Regenerative Medicine, Cell and Tissue Bank, Chair of Urology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, 85-094, Marii Sklodowskiej Curie 9 Street, 85-094, Bydgoszcz, Poland
| | - Daria Balcerczyk
- Department of Regenerative Medicine, Cell and Tissue Bank, Chair of Urology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, 85-094, Marii Sklodowskiej Curie 9 Street, 85-094, Bydgoszcz, Poland
| | - Jan Adamowicz
- Department of Regenerative Medicine, Cell and Tissue Bank, Chair of Urology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, 85-094, Marii Sklodowskiej Curie 9 Street, 85-094, Bydgoszcz, Poland
| | - Karolina Warda
- Department of Regenerative Medicine, Cell and Tissue Bank, Chair of Urology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, 85-094, Marii Sklodowskiej Curie 9 Street, 85-094, Bydgoszcz, Poland
| | - Lukasz Buchholz
- Department of Regenerative Medicine, Cell and Tissue Bank, Chair of Urology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, 85-094, Marii Sklodowskiej Curie 9 Street, 85-094, Bydgoszcz, Poland
| | - Tomasz Drewa
- Department of Regenerative Medicine, Cell and Tissue Bank, Chair of Urology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, 85-094, Marii Sklodowskiej Curie 9 Street, 85-094, Bydgoszcz, Poland
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23
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Fakhrieh M, Darvish M, Ardeshirylajimi A, Taheri M, Omrani MD. Improved bladder smooth muscle cell differentiation of the mesenchymal stem cells when grown on electrospun polyacrylonitrile/polyethylene oxide nanofibrous scaffold. J Cell Biochem 2019; 120:15814-15822. [PMID: 31069835 DOI: 10.1002/jcb.28852] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 02/27/2019] [Indexed: 11/08/2022]
Abstract
Reconstruction of the bladder wall plays an important role in improving its function in patients with urinary bladder dysfunction. Tissue engineering has been trying to introduce biocompatible nanofibers as scaffolds for bladder wall matrix substitutes. In this study a composite nanofibrous scaffold was fabricated from polyacrylonitrile (PAN) and polyethylene oxide (PEO) blend by electrospinning method and then its morphological and mechanical characteristics was evaluated by scanning electron microscopy (SEM), tensile, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Then smooth muscle cell (SMC) differentiation supportive capacity of PAN-PEO nanofibers was investigated by culturing of human adipose tissue-derived mesenchymal stem cells (AT-MSCs) on this scaffold and then its differentiation potential in different groups was investigated using SMC-related gene and protein markers. SEM and MTT results demonstrated that PAN-PEO supported AT-MSCs attachment, growth and proliferation, especially at early times after cell seeding. The obtained results from real-time reverse transcription polymerase chain reaction revealed that collagen-I-α1, collagen-III-α1, α-smooth muscle actin (α-SMA), calponin1, SM22α, caldesmon1, elastin, and myosin heavy chain (MHC) genes were expressed in AT-MSCs cultured on PAN-PEO significantly higher than those stem cells that cultured on the culture plate as a control. In addition α-SMA and MHC proteins were also expressed in AT-MSCs cultured on PAN-PEO significantly higher than control. According to the results PAN-PEO nanofibrous scaffold showed a positive AT-MSCs-seeded PAN-PEO has a great promising potential to use in bladder tissue engineering applications.
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Affiliation(s)
- Maryam Fakhrieh
- Department of Biotechnology, University of Tehran, Tehran, Iran
| | - Maryam Darvish
- Department of Medical Biotechnology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran
| | - Abdolreza Ardeshirylajimi
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Taheri
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mir Davood Omrani
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Urology and nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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24
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Abstract
PURPOSE OF REVIEW The current review provides an update on recent advances in stem cell biology relevant to female reproduction. RECENT FINDINGS Stem cells are undifferentiated cells that often serve as a reservoir of cells to regenerate tissue in settings or injury or cell loss. The endometrium has progenitor stem cells that can replace all of the endometrium during each menstrual cycle. In addition, multipotent endometrial cells replace these progenitor cells when depleted. Recruitment of stem cells from outside of the uterus occurs in setting of increased demand such as ischemia or injury. Bone marrow-derived multipotent stem cells are recruited to the uterus by estrogen or injury-induced expression of the chemokine CXCL12. In the setting of overwhelming injury, especially in the setting of low estrogen levels, there may be insufficient stem cell recruitment to adequately repair the uterus resulting in conditions such as Asherman syndrome or other endometrial defects. In contrast, excessive recruitment of stem cells underlies endometriosis. Enhanced understanding of stem-cell mobilization, recruitment, and engraftment has created the possibility of improved therapy for endometrial defects and endometriosis through enhanced manipulation of stem-cell trafficking. Further, the normal endometrium is a rich source of multipotent stem cells that can be used for numerous applications in regenerative medicine beyond reproduction. SUMMARY A better understanding of reproductive stem-cell biology may allow improved treatment of endometrial disease such as Asherman syndrome and other endometrial receptivity defects. Inhibiting stem-cell mobilization may also be helpful in endometriosis therapy. Finally, endometrial derived multipotent stem cells may play a crucial role in cell therapy for regenerative medicine.
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25
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Pokrywczynska M, Jundzill A, Warda K, Buchholz L, Rasmus M, Adamowicz J, Bodnar M, Marszalek A, Helmin-Basa A, Michalkiewicz J, Gagat M, Grzanka A, Frontczak-Baniewicz M, Gastecka AM, Kloskowski T, Nowacki M, Ricordi C, Drewa T. Does the Mesenchymal Stem Cell Source Influence Smooth Muscle Regeneration in Tissue-Engineered Urinary Bladders? Cell Transplant 2018; 26:1780-1791. [PMID: 29338385 PMCID: PMC5784518 DOI: 10.1177/0963689717722787] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
A variety of tissue engineering techniques utilizing different cells and biomaterials are currently being explored to construct urinary bladder walls de novo, but so far no approach is clearly superior. The aim of this study was to determine whether mesenchymal stem cells (MSCs) isolated from different sources, (bone marrow [BM-MSCs] and adipose tissue [ADSCs]), differ in their potential to regenerate smooth muscles in tissue-engineered urinary bladders and to determine an optimal number of MSCs for urinary bladder smooth muscle regeneration. Forty-eight rats underwent hemicystectomy and bladder augmentation with approximately 0.8 cm2 graft. In the first and second groups, urinary bladders were reconstructed with small intestinal submucosa (SIS) seeded with 10 × 106 or 4 × 106 ADSCs/cm2, respectively. In the third and fourth groups, urinary bladders were augmented with SIS seeded with 10 × 106 or 4 × 106 BM-MSCs/cm2, respectively. In the fifth group, urinary bladders were augmented with SIS without cells. The sixth group (control) was left intact. Smooth muscle regeneration was evaluated by real-time polymerase chain reaction (RT-PCR) and histological examinations. Histologically, there were no significant differences between urinary bladders augmented with ADSCs and BM-MSCs, but there was a marked increase in smooth muscle formation in bladders augmented with grafts seeded with MSCs in higher density (10 × 106/cm2) compared to lower density (4 × 106/cm2). Molecular analysis revealed that bladders reconstructed with ADSC-seeded grafts expressed higher levels of smooth muscle myosin heavy chain, caldesmon, and vinculin. Bladders augmented with unseeded SIS were fibrotic and devoid of smooth muscles. ADSCs and BM-MSCs have comparable smooth muscle regenerative potential, but the number of MSCs used for graft preparation significantly affects the smooth muscle content in tissue-engineered urinary bladders.
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Affiliation(s)
- Marta Pokrywczynska
- 1 Department of Regenerative Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.,2 The Diabetes Research Institute Federation, Miami, FL, USA.,3 The Cure Alliance, Miami, FL, USA
| | - Arkadiusz Jundzill
- 1 Department of Regenerative Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland
| | - Karolina Warda
- 1 Department of Regenerative Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland
| | - Lukasz Buchholz
- 1 Department of Regenerative Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland
| | - Marta Rasmus
- 1 Department of Regenerative Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland
| | - Jan Adamowicz
- 1 Department of Regenerative Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland
| | - Magdalena Bodnar
- 4 Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland
| | - Andrzej Marszalek
- 5 Department of Tumor Pathology, Center of Oncology, Poznan University of Medical Sciences, Poznan, Poland
| | - Anna Helmin-Basa
- 6 Department of Immunology, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland
| | - Jacek Michalkiewicz
- 6 Department of Immunology, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland
| | - Maciej Gagat
- 7 Department of Embryology and Histology, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland
| | - Alina Grzanka
- 7 Department of Embryology and Histology, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland
| | | | - Agata Magdalena Gastecka
- 1 Department of Regenerative Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland
| | - Tomasz Kloskowski
- 1 Department of Regenerative Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland
| | - Maciej Nowacki
- 1 Department of Regenerative Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland
| | - Camillo Ricordi
- 2 The Diabetes Research Institute Federation, Miami, FL, USA.,3 The Cure Alliance, Miami, FL, USA.,9 Diabetes Research Institute and Cell Transplant Program, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Tomasz Drewa
- 1 Department of Regenerative Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland
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Catry J, Luong-Nguyen M, Arakelian L, Poghosyan T, Bruneval P, Domet T, Michaud L, Sfeir R, Gottrand F, Larghero J, Vanneaux V, Cattan P. Circumferential Esophageal Replacement by a Tissue-engineered Substitute Using Mesenchymal Stem Cells: An Experimental Study in Mini Pigs. Cell Transplant 2018; 26:1831-1839. [PMID: 29390879 PMCID: PMC5802636 DOI: 10.1177/0963689717741498] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Tissue engineering appears promising as an alternative technique for esophageal replacement. Mesenchymal stem cells (MSCs) could be of interest for esophageal regeneration. Evaluation of the ability of an acellular matrix seeded with autologous MSCs to promote tissue remodeling toward an esophageal phenotype after circumferential replacement of the esophagus in a mini pig model. A 3 cm long circumferential replacement of the abdominal esophagus was performed with an MSC-seeded matrix (MSC group, n = 10) versus a matrix alone (control group, n = 10), which has previously been matured into the great omentum. The graft area was covered with an esophageal removable stent. A comparative histological analysis of the graft area after animals were euthanized sequentially is the primary outcome of the study. Histological findings after maturation, overall animal survival, and postoperative morbidity were also compared between groups. At postoperative day 45 (POD 45), a mature squamous epithelium covering the entire surface of the graft area was observed in all the MSC group specimens but in none of the control group before POD 95. Starting at POD 45, desmin positive cells were seen in the graft area in the MSC group but never in the control group. There were no differences between groups in the incidence of surgical complications and postoperative death. In this model, MSCs accelerate the mature re-epitheliazation and early initiation of muscle cell colonization. Further studies will focus on the use of cell tracking tools in order to analyze the becoming of these cells and the mechanisms involved in this tissue regeneration.
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Affiliation(s)
- Jonathan Catry
- 1 Cell Therapy Unit and CIC-BT, AP-HP, Saint-Louis Hospital, Paris, France.,2 Department of Digestive and Endocrine Surgery, AP-HP, Saint-Louis Hospital, Paris, France.,3 Inserm UMR 1160, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Minh Luong-Nguyen
- 1 Cell Therapy Unit and CIC-BT, AP-HP, Saint-Louis Hospital, Paris, France.,2 Department of Digestive and Endocrine Surgery, AP-HP, Saint-Louis Hospital, Paris, France.,3 Inserm UMR 1160, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Lousineh Arakelian
- 1 Cell Therapy Unit and CIC-BT, AP-HP, Saint-Louis Hospital, Paris, France
| | - Tigran Poghosyan
- 1 Cell Therapy Unit and CIC-BT, AP-HP, Saint-Louis Hospital, Paris, France.,2 Department of Digestive and Endocrine Surgery, AP-HP, Saint-Louis Hospital, Paris, France.,3 Inserm UMR 1160, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Patrick Bruneval
- 4 Department of Pathology, AP-HP, Georges Pompidou European Hospital, Paris, France
| | - Thomas Domet
- 1 Cell Therapy Unit and CIC-BT, AP-HP, Saint-Louis Hospital, Paris, France
| | - Laurent Michaud
- 5 Reference Center for Congenital and Malformative Esophageal Diseases, Department of Pediatric Gastroenterology and Nutrition, Jeanne de Flandre Hospital, Université Lille 2, Lille, France
| | - Rony Sfeir
- 6 Department of Pediatric Surgery, Jeanne de Flandre Hospital, University Lille 2, Lille, France
| | - Frederic Gottrand
- 5 Reference Center for Congenital and Malformative Esophageal Diseases, Department of Pediatric Gastroenterology and Nutrition, Jeanne de Flandre Hospital, Université Lille 2, Lille, France
| | - Jerome Larghero
- 1 Cell Therapy Unit and CIC-BT, AP-HP, Saint-Louis Hospital, Paris, France.,3 Inserm UMR 1160, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Valerie Vanneaux
- 1 Cell Therapy Unit and CIC-BT, AP-HP, Saint-Louis Hospital, Paris, France.,3 Inserm UMR 1160, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Pierre Cattan
- 1 Cell Therapy Unit and CIC-BT, AP-HP, Saint-Louis Hospital, Paris, France.,2 Department of Digestive and Endocrine Surgery, AP-HP, Saint-Louis Hospital, Paris, France.,3 Inserm UMR 1160, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
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Pokrywczynska M, Jundzill A, Rasmus M, Adamowicz J, Balcerczyk D, Buhl M, Warda K, Buchholz L, Gagat M, Grzanka D, Drewa T. Understanding the role of mesenchymal stem cells in urinary bladder regeneration-a preclinical study on a porcine model. Stem Cell Res Ther 2018; 9:328. [PMID: 30486856 PMCID: PMC6260700 DOI: 10.1186/s13287-018-1070-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 10/20/2018] [Accepted: 11/08/2018] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The tissue engineering of urinary bladder advances rapidly reflecting clinical need for a new kind of therapeutic solution for patients requiring urinary bladder replacement. Majority of the bladder augmentation studies have been performed in small rodent or rabbit models. Insufficient number of studies examining regenerative capacity of tissue-engineered graft in urinary bladder augmentation in a large animal model does not allow for successful translation of this technology to the clinical setting. The aim of this study was to evaluate the role of adipose-derived stem cells (ADSCs) in regeneration of clinically significant urinary bladder wall defect in a large animal model. METHODS ADSCs isolated from a superficial abdominal Camper's fascia were labeled with PKH-26 tracking dye and subsequently seeded into bladder acellular matrix (BAM) grafts. Pigs underwent hemicystectomy followed by augmentation cystoplasty with BAM only (n = 10) or BAM seeded with autologous ADSCs (n = 10). Reconstructed bladders were subjected to macroscopic, histological, immunofluoresence, molecular, and radiological evaluations at 3 months post-augmentation. RESULTS Sixteen animals (n = 8 for each group) survived the 3-month follow-up without serious complications. Tissue-engineered bladder function was normal without any signs of post-voiding urine residual in bladders and in the upper urinary tracts. ADSCs enhanced regeneration of tissue-engineered urinary bladder but the process was incomplete in the central graft region. Only a small percentage of implanted ADSCs survived and differentiated into smooth muscle and endothelial cells. CONCLUSIONS The data demonstrate that ADSCs support regeneration of large defects of the urinary bladder wall but the process is incomplete in the central graft region. Stem cells enhance urinary bladder regeneration indirectly through paracrine effect.
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Affiliation(s)
- Marta Pokrywczynska
- Department of Regenerative Medicine, Cell and Tissue Bank, Chair of Urology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, Marii Sklodowskiej Curie 9 Street, 85-094 Bydgoszcz, Poland
| | - Arkadiusz Jundzill
- Department of Regenerative Medicine, Cell and Tissue Bank, Chair of Urology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, Marii Sklodowskiej Curie 9 Street, 85-094 Bydgoszcz, Poland
| | - Marta Rasmus
- Department of Regenerative Medicine, Cell and Tissue Bank, Chair of Urology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, Marii Sklodowskiej Curie 9 Street, 85-094 Bydgoszcz, Poland
| | - Jan Adamowicz
- Department of Regenerative Medicine, Cell and Tissue Bank, Chair of Urology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, Marii Sklodowskiej Curie 9 Street, 85-094 Bydgoszcz, Poland
| | - Daria Balcerczyk
- Department of Regenerative Medicine, Cell and Tissue Bank, Chair of Urology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, Marii Sklodowskiej Curie 9 Street, 85-094 Bydgoszcz, Poland
| | - Monika Buhl
- Department of Regenerative Medicine, Cell and Tissue Bank, Chair of Urology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, Marii Sklodowskiej Curie 9 Street, 85-094 Bydgoszcz, Poland
| | - Karolina Warda
- Department of Regenerative Medicine, Cell and Tissue Bank, Chair of Urology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, Marii Sklodowskiej Curie 9 Street, 85-094 Bydgoszcz, Poland
| | - Lukasz Buchholz
- Department of Regenerative Medicine, Cell and Tissue Bank, Chair of Urology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, Marii Sklodowskiej Curie 9 Street, 85-094 Bydgoszcz, Poland
| | - Maciej Gagat
- Department of Embryology and Histology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, 85-092 Bydgoszcz, Poland
| | - Dariusz Grzanka
- Department of Clinical Pathomorphology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, 85-094 Bydgoszcz, Poland
| | - Tomasz Drewa
- Department of Regenerative Medicine, Cell and Tissue Bank, Chair of Urology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz, Marii Sklodowskiej Curie 9 Street, 85-094 Bydgoszcz, Poland
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28
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Zhang N, Qin X, Zhang J, Zhang Z, Li Y, Xie Y, Kong D, Du R, Huang X, Xu Y. Bone Marrow Mesenchymal Stem Cells Accelerate the Morphological and Functional Recovery of Neovaginas. Artif Organs 2018; 42:1206-1215. [DOI: 10.1111/aor.13297] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Revised: 04/18/2018] [Accepted: 05/24/2018] [Indexed: 12/14/2022]
Affiliation(s)
- Ning Zhang
- Department of Obstetrics and Gynecology; The Second Hospital of Hebei Medical University
| | - Xijing Qin
- Department of Obstetrics and Gynecology; The Second Hospital of Hebei Medical University
| | - Jingkun Zhang
- Department of Obstetrics and Gynecology; The Second Hospital of Hebei Medical University
| | - Zhiqiang Zhang
- Department of Obstetrics and Gynecology; The Second Hospital of Hebei Medical University
| | - Yanan Li
- Department of Obstetrics and Gynecology; The Second Hospital of Hebei Medical University
| | - Yanling Xie
- Department of Obstetrics and Gynecology; The Second Hospital of Hebei Medical University
| | - Desheng Kong
- Department of Obstetrics and Gynecology; The Second Hospital of Hebei Medical University
| | - Runxuan Du
- Department of Obstetrics and Gynecology; The Second Hospital of Hebei Medical University
| | - Xianghua Huang
- Department of Obstetrics and Gynecology; The Second Hospital of Hebei Medical University
| | - Yanfang Xu
- Department of Pharmacology; Hebei Medical University; Shijiazhuang China
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29
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Langer S, Radtke C, Györi E, Springer A, Metzelder ML. Bladder augmentation in children: current problems and experimental strategies for reconstruction. Wien Med Wochenschr 2018; 169:61-70. [PMID: 30084093 PMCID: PMC6394595 DOI: 10.1007/s10354-018-0645-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 06/21/2018] [Indexed: 12/31/2022]
Abstract
Bladder augmentation is a demanding surgical procedure and exclusively offered for selected children and has only a small spectrum of indications. Paediatric bladder voiding dysfunction occurs either on a basis of neurological dysfunction caused by congenital neural tube defects or on a basis of rare congenital anatomic malformations. Neurogenic bladder dysfunction often responds well to a combination of specific drugs and/or intermittent self-catheterization. However, selected patients with spinal dysraphism and children with congenital malformations like bladder exstrophy and resulting small bladder capacity might require bladder augmentation. Ileocystoplasty is the preferred method of bladder augmentation to date. Because of the substantial long-and short-term morbidity of augmentation cystoplasty, recent studies have tried to incorporate new techniques and technologies, such as the use of biomaterials to overcome or reduce the adverse effects. In this regard, homografts and allografts have been implemented in bladder augmentation with varying results, but recent studies have shown promising data in terms of proliferation of urothelium and muscle cells by using biological silk grafts.
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Affiliation(s)
- Sophie Langer
- General Hospital Vienna, Clinical Department of Paediatric Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Christine Radtke
- General Hospital Vienna, Clinical Department of Plastic and Reconstructive Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Eva Györi
- General Hospital Vienna, Clinical Department of Plastic and Reconstructive Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Alexander Springer
- General Hospital Vienna, Clinical Department of Paediatric Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Martin L Metzelder
- General Hospital Vienna, Clinical Department of Paediatric Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
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30
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Zhou L, Xia J, Wang P, Jia R, Zheng J, Yao X, Chen Y, Dai Y, Yang B. Autologous Smooth Muscle Progenitor Cells Enhance Regeneration of Tissue-Engineered Bladder. Tissue Eng Part A 2018; 24:1066-1081. [PMID: 29327677 DOI: 10.1089/ten.tea.2017.0376] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Liuhua Zhou
- Department of Urology and Andrology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Jiadong Xia
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Pengji Wang
- Department of Urology and Andrology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China
- Department of Urology, Longkou People Hospital, Yantai, China
| | - Ruipeng Jia
- Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Junhua Zheng
- Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xudong Yao
- Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yun Chen
- Department of Urology and Andrology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Yutian Dai
- Department of Urology and Andrology, Affiliated Drum Tower Hospital, Nanjing University School of Medicine, Nanjing, China
| | - Bin Yang
- Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
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31
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Zhou Z, Yan H, Liu Y, Xiao D, Li W, Wang Q, Zhao Y, Sun K, Zhang M, Lu M. Adipose-derived stem-cell-implanted poly(ϵ-caprolactone)/chitosan scaffold improves bladder regeneration in a rat model. Regen Med 2018; 13:331-342. [PMID: 29717628 DOI: 10.2217/rme-2017-0120] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
AIM The study investigated the feasibility of seeding adipose-derived stem cells (ASCs) onto a poly(ϵ-caprolactone)/chitosan (PCL/CS) scaffold for bladder reconstruction using a rat model of bladder augmentation. MATERIALS & METHODS In the experimental group, the autologous ASCs were seeded onto the PCL/CS scaffold for bladder augmentation. An unseeded scaffold was used for bladder augmentation as control group. The sham group was also set. RESULT 8 weeks after implantation, more densely smooth muscles were detected in the experimental group with a larger bladder capacity and more intensive blood vessels. Immunofluorescence staining demonstrated that some of the smooth muscle cells were transdifferentiated from the ASCs. CONCLUSION Our findings indicated that ASC-seeded PCL/CS may be a potential scaffold for bladder tissue engineering.
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Affiliation(s)
- Zhe Zhou
- Department of Urology & Andrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
| | - Hao Yan
- Department of Urology & Andrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
| | - Yidong Liu
- Department of Urology & Andrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
| | - Dongdong Xiao
- Department of Urology & Andrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
| | - Wei Li
- State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Qiong Wang
- Department of Urology, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
| | - Yang Zhao
- Department of Urology & Andrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
| | - Kang Sun
- State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Ming Zhang
- Department of Urology & Andrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
| | - Mujun Lu
- Department of Urology & Andrology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China
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32
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Ajalloueian F, Lemon G, Hilborn J, Chronakis IS, Fossum M. Bladder biomechanics and the use of scaffolds for regenerative medicine in the urinary bladder. Nat Rev Urol 2018; 15:155-174. [DOI: 10.1038/nrurol.2018.5] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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33
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Johnson SC, Smith ZL, Sack BS, Steinberg GD. Tissue Engineering and Conduit Substitution. Urol Clin North Am 2018; 45:133-141. [DOI: 10.1016/j.ucl.2017.09.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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34
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Robb KP, Shridhar A, Flynn LE. Decellularized Matrices As Cell-Instructive Scaffolds to Guide Tissue-Specific Regeneration. ACS Biomater Sci Eng 2017; 4:3627-3643. [PMID: 33429606 DOI: 10.1021/acsbiomaterials.7b00619] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Decellularized scaffolds are promising clinically translational biomaterials that can be applied to direct cell responses and promote tissue regeneration. Bioscaffolds derived from the extracellular matrix (ECM) of decellularized tissues can naturally mimic the complex extracellular microenvironment through the retention of compositional, biomechanical, and structural properties specific to the native ECM. Increasingly, studies have investigated the use of ECM-derived scaffolds as instructive substrates to recapitulate properties of the stem cell niche and guide cell proliferation, paracrine factor production, and differentiation in a tissue-specific manner. Here, we review the application of decellularized tissue scaffolds as instructive matrices for stem or progenitor cells, with a focus on the mechanisms through which ECM-derived scaffolds can mediate cell behavior to promote tissue-specific regeneration. We conclude that although additional preclinical studies are required, ECM-derived scaffolds are a promising platform to guide cell behavior and may have widespread clinical applications in the field of regenerative medicine.
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Affiliation(s)
- Kevin P Robb
- Biomedical Engineering Graduate Program, The University of Western Ontario, Claudette MacKay Lassonde Pavilion, London, Ontario, Canada N6A 5B9
| | - Arthi Shridhar
- Department of Chemical and Biochemical Engineering, The University of Western Ontario, Thompson Engineering Building, London, Ontario, Canada N6A 5B9
| | - Lauren E Flynn
- Department of Chemical and Biochemical Engineering, The University of Western Ontario, Thompson Engineering Building, London, Ontario, Canada N6A 5B9.,Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada N6A 5C1
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35
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Is Human Embryonic Stem Cell (HESC) Research Still Necessary Today? Asian Bioeth Rev 2017. [DOI: 10.1007/s41649-017-0010-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
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36
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Xu Q, Shanti RM, Zhang Q, Cannady SB, O'Malley BW, Le AD. A Gingiva-Derived Mesenchymal Stem Cell-Laden Porcine Small Intestinal Submucosa Extracellular Matrix Construct Promotes Myomucosal Regeneration of the Tongue. Tissue Eng Part A 2017; 23:301-312. [PMID: 27923325 DOI: 10.1089/ten.tea.2016.0342] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
In the oral cavity, the tongue is the anatomic subsite most commonly involved by invasive squamous cell carcinoma. Current treatment protocols often require significant tissue resection to achieve adequate negative margins and optimal local tumor control. Reconstruction of the tongue while preserving and/or restoring its critical vocal, chewing, and swallowing functions remains one of the major challenges in head and neck oncologic surgery. We investigated the in vitro feasibility of fabricating a novel combinatorial construct using porcine small intestinal submucosa extracellular matrix (SIS-ECM) and human gingiva-derived mesenchymal stem cells (GMSCs) as a GMSC/SIS-ECM tissue graft for the tongue reconstruction. We developed a rat model of critical-sized myomucosal defect of the tongue that allowed the testing of therapeutic effects of an acellular SIS-ECM construct versus a GMSC/SIS-ECM construct on repair and regeneration of the tongue defect. We showed that the GMSC/SIS-ECM construct engrafted at the host recipient site, promoted soft tissue healing, and regenerated the muscular layer, compared to the SIS-ECM alone or nontreated defect controls. Furthermore, our results revealed that transplantation of the GMSC/SIS-ECM construct significantly increased the expression of several myogenic transcriptional factors and simultaneously suppressed the expression of type I collagen at the wounded area of the tongue. These compelling findings suggest that, unlike the tongue contracture and fibrosis of the nontreated defect group, transplantation of the combinatorial GMSC/SIS-ECM constructs accelerates wound healing and muscle regeneration and maintains the overall tongue shape, possibly by both enhancing the function of endogenous skeletal progenitor cells and suppressing fibrosis. Together, our findings indicate that GMSC/SIS-ECM potentially served as a myomucosal graft for tongue reconstruction postsurgery of head and neck cancer.
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Affiliation(s)
- Qilin Xu
- 1 Department of Oral and Maxillofacial Surgery and Pharmacology, University of Pennsylvania School of Dental Medicine , Philadelphia, Pennsylvania
| | - Rabie M Shanti
- 1 Department of Oral and Maxillofacial Surgery and Pharmacology, University of Pennsylvania School of Dental Medicine , Philadelphia, Pennsylvania.,2 Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania.,3 Department of Oral and Maxillofacial Surgery, Penn Medicine Hospital of the University of Pennsylvania , Philadelphia, Pennsylvania
| | - Qunzhou Zhang
- 1 Department of Oral and Maxillofacial Surgery and Pharmacology, University of Pennsylvania School of Dental Medicine , Philadelphia, Pennsylvania
| | - Steven B Cannady
- 2 Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania
| | - Bert W O'Malley
- 2 Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania
| | - Anh D Le
- 1 Department of Oral and Maxillofacial Surgery and Pharmacology, University of Pennsylvania School of Dental Medicine , Philadelphia, Pennsylvania.,3 Department of Oral and Maxillofacial Surgery, Penn Medicine Hospital of the University of Pennsylvania , Philadelphia, Pennsylvania
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Chou KJ, Lee PT, Chen CL, Hsu CY, Huang WC, Huang CW, Fang HC. CD44 fucosylation on mesenchymal stem cell enhances homing and macrophage polarization in ischemic kidney injury. Exp Cell Res 2016; 350:91-102. [PMID: 27871849 DOI: 10.1016/j.yexcr.2016.11.010] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Revised: 11/01/2016] [Accepted: 11/15/2016] [Indexed: 01/14/2023]
Abstract
The lack of homing ability possibly reduces the healing potential of bone-marrow-derived mesenchymal stem cells (MSCs). Therefore, transforming native CD44 on MSCs into a hematopoietic cell E-/L-selectin ligand (HCELL) that possesses potent E-selectin affinity might enhance the homing and regenerative abilities of MSCs. Through fucosyltransferase VI (FTVI) transfection, MSCs were fucosylated on N-glycans of CD44 to become HCELL positive, thus interacting with E-selectin on injured endothelial cells. HCELL expression facilitated MSC homing in kidneys within 24h after injury and reduced lung stasis. An in vitro adhesion assay revealed that transfection enhanced the association between MSCs and hypoxic endothelial cells. In mice treated with HCELL-positive MSCs, the injured kidneys exhibited clusters of homing MSCs, whereas MSCs were rarely observed in mouse kidneys treated with HCELL-negative MSCs. Most MSCs were initially localized at the renal capsule, and some MSCs later migrated inward between tubules. Most homing MSCs were in close contact with inflammatory cells without tubular transdifferentiation. Furthermore, HCELL-positive MSCs substantially alleviated renal injury, partly by enhancing the polarization of infiltrating macrophages. In conclusion, engineering the glycan of CD44 on MSCs through FTVI transfection might enhance renotropism and the regenerating ability of MSCs in ischemic kidney injury.
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Affiliation(s)
- Kang-Ju Chou
- Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Po-Tsang Lee
- Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chien-Liang Chen
- Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chih-Yang Hsu
- Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Wei-Chieh Huang
- Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Chien-Wei Huang
- Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Hua-Chang Fang
- Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
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38
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Mahla RS. Stem Cells Applications in Regenerative Medicine and Disease Therapeutics. Int J Cell Biol 2016; 2016:6940283. [PMID: 27516776 PMCID: PMC4969512 DOI: 10.1155/2016/6940283] [Citation(s) in RCA: 332] [Impact Index Per Article: 36.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2016] [Accepted: 06/05/2016] [Indexed: 12/18/2022] Open
Abstract
Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation.
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Affiliation(s)
- Ranjeet Singh Mahla
- Department of Biological Sciences, Indian Institute of Science Education and Research (IISER), Bhopal, Madhya Pradesh 462066, India
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39
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Chang CW, Petrie T, Clark A, Lin X, Sondergaard CS, Griffiths LG. Mesenchymal Stem Cell Seeding of Porcine Small Intestinal Submucosal Extracellular Matrix for Cardiovascular Applications. PLoS One 2016; 11:e0153412. [PMID: 27070546 PMCID: PMC4829265 DOI: 10.1371/journal.pone.0153412] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Accepted: 03/29/2016] [Indexed: 01/16/2023] Open
Abstract
In this study, we investigate the translational potential of a novel combined construct using an FDA-approved decellularized porcine small intestinal submucosa extracellular matrix (SIS-ECM) seeded with human or porcine mesenchymal stem cells (MSCs) for cardiovascular indications. With the emerging success of individual component in various clinical applications, the combination of SIS-ECM with MSCs could provide additional therapeutic potential compared to individual components alone for cardiovascular repair. We tested the in vitro effects of MSC-seeding on SIS-ECM on resultant construct structure/function properties and MSC phenotypes. Additionally, we evaluated the ability of porcine MSCs to modulate recipient graft-specific response towards SIS-ECM in a porcine cardiac patch in vivo model. Specifically, we determined: 1) in vitro loading-capacity of human MSCs on SIS-ECM, 2) effect of cell seeding on SIS-ECM structure, compositions and mechanical properties, 3) effect of SIS-ECM seeding on human MSC phenotypes and differentiation potential, and 4) optimal orientation and dose of porcine MSCs seeded SIS-ECM for an in vivo cardiac application. In this study, histological structure, biochemical compositions and mechanical properties of the FDA-approved SIS-ECM biomaterial were retained following MSCs repopulation in vitro. Similarly, the cellular phenotypes and differentiation potential of MSCs were preserved following seeding on SIS-ECM. In a porcine in vivo patch study, the presence of porcine MSCs on SIS-ECM significantly reduced adaptive T cell response regardless of cell dose and orientation compared to SIS-ECM alone. These findings substantiate the clinical translational potential of combined SIS-ECM seeded with MSCs as a promising therapeutic candidate for cardiac applications.
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Affiliation(s)
- Chia Wei Chang
- Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, California, United States of America
| | - Tye Petrie
- Department of Surgery, School of Medicine, University of California, Davis, Sacramento, California, United States of America
| | - Alycia Clark
- Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, California, United States of America
| | - Xin Lin
- Department of Surgery, School of Medicine, University of California, Davis, Sacramento, California, United States of America
| | - Claus S. Sondergaard
- Department of Surgery, School of Medicine, University of California, Davis, Sacramento, California, United States of America
| | - Leigh G. Griffiths
- Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, California, United States of America
- * E-mail:
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Abstract
Lower urinary tract symptoms can significantly impact quality of life. Current standard treatments are not always effective and are associated with complications and side effects. The discovery of stem cells led to research into cell-based therapies for treatment of disorders of voiding dysfunction. Bone marrow mesenchymal stem cells are particularly promising given their ability to differentiate into a variety of cell types. Recent studies have investigated bone marrow stem cells to treat a number of functional voiding pathologies including bladder outlet obstruction, neurogenic bladder, and stress urinary incontinence. Experiments in tissue regeneration have also attempted to create artificial bladders and urethras. The purpose of this article is to critically review the literature regarding the use of bone marrow mesenchymal stem cells in treatment of voiding dysfunction.
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Jaimes-Parra BD, Valle-Díaz de la Guardia F, Arrabal-Polo MÁ, Herrera-Imbroda B, Lara MF, Machuca-Santa-Cruz FJ, Campos A, Alaminos M, Crespo PV, Garzón I. Ex vivo construction of a novel model of bioengineered bladder mucosa: A preliminary study. Int J Urol 2015; 23:85-92. [PMID: 26502190 DOI: 10.1111/iju.12963] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2015] [Accepted: 09/08/2015] [Indexed: 01/11/2023]
Abstract
OBJECTIVE To generate and to evaluate ex vivo a novel model of bioengineered human bladder mucosa based on fibrin-agarose biomaterials. METHODS We first established primary cultures of stromal and epithelial cells from small biopsies of the human bladder using enzymatic digestion and selective cell culture media. Then, a bioengineered substitute of the bladder lamina propria was generated using cultured stromal cells and fibrin-agarose scaffolds, and the epithelial cells were then subcultured on top to generate a complete bladder mucosa substitute. Evaluation of this substitute was carried out by cell viability and histological analyses, immunohistochemistry for key epithelial markers and transmission electron microscopy. RESULTS The results show a well-configured stroma substitute with a single-layer epithelium on top. This substitute was equivalent to the control bladder mucosa. After 7 days of ex vivo development, the epithelial layer expressed pancytokeratin, and cytokeratins CK7, CK8 and CK13, as well as filaggrin and ZO-2, with negative expression of CK4 and uroplakin III. A reduction of the expression of CK8, filaggrin and ZO-2 was found at day 14 of development. An immature basement membrane was detected at the transition between the epithelium and the lamina propria, with the presence of epithelial hemidesmosomes, interdigitations and immature desmosomes. CONCLUSIONS The present results suggest that this model of bioengineered human bladder mucosa shared structural and functional similarities with the native bladder mucosa, although the epithelial cells were not fully differentiated ex vivo. We hypothesize that this bladder mucosa substitute could have potential clinical usefulness after in vivo implantation.
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Affiliation(s)
- Boris D Jaimes-Parra
- Department of Histology (Tissue Engineering Group), University of Granada, Granada, Spain.,Biomedical Research Institute, University of Granada, Granada, Spain.,PhD Program in Biomedicine, University of Granada, Granada, Spain
| | | | | | | | - María F Lara
- Division of Urology and Urology Unit Research, Virgen de la Victoria Hospital, Malaga, Spain
| | | | - Antonio Campos
- Department of Histology (Tissue Engineering Group), University of Granada, Granada, Spain.,Biomedical Research Institute, University of Granada, Granada, Spain
| | - Miguel Alaminos
- Department of Histology (Tissue Engineering Group), University of Granada, Granada, Spain.,Biomedical Research Institute, University of Granada, Granada, Spain
| | - Pascual V Crespo
- Department of Histology (Tissue Engineering Group), University of Granada, Granada, Spain.,Biomedical Research Institute, University of Granada, Granada, Spain
| | - Ingrid Garzón
- Department of Histology (Tissue Engineering Group), University of Granada, Granada, Spain.,Biomedical Research Institute, University of Granada, Granada, Spain
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Burmeister D, Bishwokarma B, AbouShwareb T, Olson J, Herco M, Tan J, Andersson KE, Christ G. The potential utility of non-invasive imaging to monitor restoration of bladder structure and function following subtotal cystectomy (STC). BMC Urol 2015; 15:103. [PMID: 26463481 PMCID: PMC4604729 DOI: 10.1186/s12894-015-0094-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Accepted: 09/25/2015] [Indexed: 12/03/2022] Open
Abstract
Background Restoration of normal bladder volume and function (i.e., bioequivalent bladder) are observed within 8 weeks of performing subtotal cystectomy (STC; removal of ~70 % of the bladder) in 12-week old rats. For analysis of bladder function in rodents, terminal urodynamic approaches are largely utilized. In the current study, we investigated the potential for Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scans to noninvasively track restoration of structure and function following STC. Methods Twelve week old female Fisher F344 rats underwent STC and were scanned via CT and/or MRI 2, 4, 8, and 12 weeks post-STC, followed by urodynamic testing. After euthanasia, bladders were excised for histological processing. Results MRI scans demonstrated an initial decline followed by a time-dependent increase to normal bladder wall thickness (BWT) by 8 weeks post-STC. Masson’s trichrome staining showed a lack of fibrosis post-STC, and also revealed that the percent of smooth muscle in the bladder wall at 2 and 4 weeks positively correlated with pre-operative baseline BWT. Moreover, increased BWT values before STC was predictive of improved bladder compliance at 2 and 4 weeks post-STC. Cystometric studies indicated that repeated MRI manipulation (i.e. bladder emptying) apparently had a negative impact on bladder capacity and compliance. A “window” of bladder volumes was identified 2 weeks post-STC via CT scanning that were commensurate with normal micturition pressures measured in the same animal 6 weeks later. Conclusions Taken together, the data indicate some limitations of “non-invasive” imaging to provide insight into bladder regeneration. Specifically, mechanical manipulation of the bladder during MRI appears to negatively impact the regenerative process per se, which highlights the importance of terminal cystometric studies.
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Affiliation(s)
- David Burmeister
- Wake Forest Institute for Regenerative Medicine, 391 Technology Way, Winston-Salem, NC, 27101, USA.
| | - Bimjhana Bishwokarma
- Wake Forest Institute for Regenerative Medicine, 391 Technology Way, Winston-Salem, NC, 27101, USA.
| | - Tamer AbouShwareb
- Wake Forest Institute for Regenerative Medicine, 391 Technology Way, Winston-Salem, NC, 27101, USA.
| | - John Olson
- Wake Forest Department of Biomolecular Imaging, Medical Center Blvd, Winston-Salem, NC, 27157, USA.
| | - Maja Herco
- Wake Forest Institute for Regenerative Medicine, 391 Technology Way, Winston-Salem, NC, 27101, USA.
| | - Josh Tan
- Wake Forest Department of Biomolecular Imaging, Medical Center Blvd, Winston-Salem, NC, 27157, USA.
| | - Karl-Erik Andersson
- Wake Forest Institute for Regenerative Medicine, 391 Technology Way, Winston-Salem, NC, 27101, USA.
| | - George Christ
- Wake Forest Institute for Regenerative Medicine, 391 Technology Way, Winston-Salem, NC, 27101, USA. .,Departments of Biomedical Engineering and Orthopaedic Surgery, and Laboratory of Regenerative Therapeutics, University of Virginia, 415 Lane Road, Charlottesville, VA, 22908, USA.
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Snow-Lisy DC, Diaz EC, Bury MI, Fuller NJ, Hannick JH, Ahmad N, Sharma AK. The Role of Genetically Modified Mesenchymal Stem Cells in Urinary Bladder Regeneration. PLoS One 2015; 10:e0138643. [PMID: 26398705 PMCID: PMC4580420 DOI: 10.1371/journal.pone.0138643] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2015] [Accepted: 08/03/2015] [Indexed: 01/01/2023] Open
Abstract
Recent studies have demonstrated that mesenchymal stem cells (MSCs) combined with CD34+ hematopoietic/stem progenitor cells (HSPCs) can function as surrogate urinary bladder cells to synergistically promote multi-faceted bladder tissue regeneration. However, the molecular pathways governing these events are unknown. The pleiotropic effects of Wnt5a and Cyr61 are known to affect aspects of hematopoiesis, angiogenesis, and muscle and nerve regeneration. Within this study, the effects of Cyr61 and Wnt5a on bladder tissue regeneration were evaluated by grafting scaffolds containing modified human bone marrow derived MSCs. These cell lines were engineered to independently over-express Wnt5a or Cyr61, or to exhibit reduced expression of Cyr61 within the context of a nude rat bladder augmentation model. At 4 weeks post-surgery, data demonstrated increased vessel number (~250 vs ~109 vessels/mm2) and bladder smooth muscle content (~42% vs ~36%) in Cyr61OX (over-expressing) vs Cyr61KD (knock-down) groups. Muscle content decreased to ~25% at 10 weeks in Cyr61KD groups. Wnt5aOX resulted in high numbers of vessels and muscle content (~206 vessels/mm2 and ~51%, respectively) at 4 weeks. Over-expressing cell constructs resulted in peripheral nerve regeneration while Cyr61KD animals were devoid of peripheral nerve regeneration at 4 weeks. At 10 weeks post-grafting, peripheral nerve regeneration was at a minimal level for both Cyr61OX and Wnt5aOX cell lines. Blood vessel and bladder functionality were evident at both time-points in all animals. Results from this study indicate that MSC-based Cyr61OX and Wnt5aOX cell lines play pivotal roles with regards to increasing the levels of functional vasculature, influencing muscle regeneration, and the regeneration of peripheral nerves in a model of bladder augmentation. Wnt5aOX constructs closely approximated the outcomes previously observed with the co-transplantation of MSCs with CD34+ HSPCs and may be specifically targeted as an alternate means to achieve functional bladder regeneration.
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Affiliation(s)
- Devon C. Snow-Lisy
- Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Urology, Chicago, IL, United States of America
| | - Edward C. Diaz
- Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Urology, Chicago, IL, United States of America
| | - Matthew I. Bury
- Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Urology, Chicago, IL, United States of America
| | - Natalie J. Fuller
- Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Urology, Chicago, IL, United States of America
| | - Jessica H. Hannick
- Department of Urology, Loyola University Health System, Maywood, IL, United States of America
| | - Nida Ahmad
- Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Urology, Chicago, IL, United States of America
| | - Arun K. Sharma
- Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric Urology, Chicago, IL, United States of America
- Northwestern University Feinberg School of Medicine, Department of Urology, Chicago, IL, United States of America
- Northwestern University, Simpson Querrey Institute for BioNanotechnology, Chicago, IL, United States of America
- Northwestern University, Department of Biomedical Engineering, Evanston, IL, United States of America
- * E-mail:
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Abstract
As bladder reconstruction strategies evolve, a feasible and safe source of transplantable urothelium becomes a major consideration for patients with advanced bladder disease, particularly cancer. Pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are attractive candidates from which to derive urothelium as they renew and proliferate indefinitely in vitro and fulfill the non-autologous and/or non-urologic criteria, respectively, that is required for many patients. This review presents the latest advancements in differentiating urothelium from pluripotent stem cells in vitro in the context of current bladder tissue engineering strategies.
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Mutlu L, Hufnagel D, Taylor HS. The endometrium as a source of mesenchymal stem cells for regenerative medicine. Biol Reprod 2015; 92:138. [PMID: 25904012 DOI: 10.1095/biolreprod.114.126771] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2014] [Accepted: 04/09/2015] [Indexed: 12/21/2022] Open
Abstract
Stem cell therapies have opened new frontiers in medicine with the possibility of regenerating lost or damaged cells. Embryonic stem cells, induced pluripotent stem cells, hematopoietic stem cells, and mesenchymal stem cells have been used to derive mature cell types for tissue regeneration and repair. However, the endometrium has emerged as an attractive, novel source of adult stem cells that are easily accessed and demonstrate remarkable differentiation capacity. In this review, we summarize our current understanding of endometrial stem cells and their therapeutic potential in regenerative medicine.
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Affiliation(s)
- Levent Mutlu
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut
| | - Demetra Hufnagel
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut
| | - Hugh S Taylor
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut
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Mauney JR, Adam RM. Dynamic reciprocity in cell-scaffold interactions. Adv Drug Deliv Rev 2015; 82-83:77-85. [PMID: 25453262 DOI: 10.1016/j.addr.2014.10.016] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2014] [Revised: 09/07/2014] [Accepted: 10/15/2014] [Indexed: 12/14/2022]
Abstract
Tissue engineering in urology has shown considerable promise. However, there is still much to understand, particularly regarding the interactions between scaffolds and their host environment, how these interactions regulate regeneration and how they may be enhanced for optimal tissue repair. In this review, we discuss the concept of dynamic reciprocity as applied to tissue engineering, i.e. how bi-directional signaling between implanted scaffolds and host tissues such as the bladder drives the process of constructive remodeling to ensure successful graft integration and tissue repair. The impact of scaffold content and configuration, the contribution of endogenous and exogenous bioactive factors, the influence of the host immune response and the functional interaction with mechanical stimulation are all considered. In addition, the temporal relationships of host tissue ingrowth, bioactive factor mobilization, scaffold degradation and immune cell infiltration, as well as the reciprocal signaling between discrete cell types and scaffolds are discussed. Improved understanding of these aspects of tissue repair will identify opportunities for optimization of repair that could be exploited to enhance regenerative medicine strategies for urology in future studies.
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Li L, Zhang D, Li P, Damaser M, Zhang Y. Virus integration and genome influence in approaches to stem cell based therapy for andro-urology. Adv Drug Deliv Rev 2015; 82-83:12-21. [PMID: 25453258 DOI: 10.1016/j.addr.2014.10.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Revised: 09/22/2014] [Accepted: 10/07/2014] [Indexed: 12/21/2022]
Abstract
Despite the potential of stem cells in cell-based therapy, major limitations such as cell retention, ingrowth, and trans-differentiation after implantation remain. One technique for genetic modification of cells for tissue repair is the introduction of specific genes using molecular biology techniques, such as virus integration, to provide a gene that adds new functions to enhance cellular function, and to secrete trophic factors for recruiting resident cells to participate in tissue repair. Stem cells can be labeled to track cell survival, migration, and lineage. Increasing evidence demonstrates that cell therapy and gene therapy in combination remarkably improve differentiation of implanted mesenchymal stromal cells (MSCs), revascularization, and innervation in genitourinary tissues, especially to treat urinary incontinence, erectile dysfunction, lower urinary tract reconstruction, and renal failure. This review discusses the benefits, safety, side effects, and alternatives for using genetically modified MSCs in tissue regeneration in andro-urology.
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Lin HK, Madihally SV, Palmer B, Frimberger D, Fung KM, Kropp BP. Biomatrices for bladder reconstruction. Adv Drug Deliv Rev 2015; 82-83:47-63. [PMID: 25477305 DOI: 10.1016/j.addr.2014.11.020] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Revised: 11/17/2014] [Accepted: 11/24/2014] [Indexed: 12/22/2022]
Abstract
There is a demand for tissue engineering of the bladder needed by patients who experience a neurogenic bladder or idiopathic detrusor overactivity. To avoid complications from augmentation cystoplasty, the field of tissue engineering seeks optimal scaffolds for bladder reconstruction. Naturally derived biomaterials as well as synthetic and natural polymers have been explored as bladder substitutes. To improve regenerative properties, these biomaterials have been conjugated with functional molecules, combined with nanotechology, or seeded with exogenous cells. Although most studies reported complete and functional bladder regeneration in small-animal models, results from large-animal models and human clinical trials varied. For functional bladder regeneration, procedures for biomaterial fabrication, incorporation of biologically active agents, introduction of nanotechnology, and application of stem-cell technology need to be standardized. Advanced molecular and medical technologies such as next generation sequencing and magnetic resonance imaging can be introduced for mechanistic understanding and non-invasive monitoring of regeneration processes, respectively.
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Affiliation(s)
- Hsueh-Kung Lin
- Department of Urology, The Children's Hospital of Oklahoma, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Sundar V Madihally
- Department of Chemical Engineering, 423 Engineering North, Oklahoma State University, Stillwater, OK 74078, USA
| | - Blake Palmer
- Department of Urology, The Children's Hospital of Oklahoma, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Dominic Frimberger
- Department of Urology, The Children's Hospital of Oklahoma, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Kar-Ming Fung
- Department of Urology, The Children's Hospital of Oklahoma, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Bradley P Kropp
- Department of Urology, The Children's Hospital of Oklahoma, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
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Lam Van Ba O, Aharony S, Loutochin O, Corcos J. Bladder tissue engineering: a literature review. Adv Drug Deliv Rev 2015; 82-83:31-7. [PMID: 25446136 DOI: 10.1016/j.addr.2014.11.013] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2014] [Revised: 10/12/2014] [Accepted: 11/08/2014] [Indexed: 12/30/2022]
Abstract
PURPOSE OF REVIEW In bladder cancer and neuro-bladder, reconstruction of the bladder requires bowel segment grafting for augmentation cystoplasty or neo-bladder creation. However, even if currently considered as the gold standard, it is associated with potentially severe short- and long-term adverse effects. Thus, bladder tissue engineering is a promising approach to bladder reconstruction. RECENT FINDINGS In the last few years, progress has been made with the development of new biomaterials for bladder tissue replacement and in deciphering the role of stem cells as well as their contribution to bladder scaffold integration and tissue regeneration. SUMMARY This review of recently published articles allows us to forecast the characteristics of efficient and safe bladder biomaterials. However, several factors, such as native bladder traits, the specific involvement of urine, and bladder tissue replacement indications, have to be assessed with caution before including bladder tissue engineering in clinical trials. Many authors agree that these challenging techniques could deliver significant benefits with clinical application, reducing morbidity and global long-term costs.
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Affiliation(s)
- Ornella Lam Van Ba
- Department of Urology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
| | - Shachar Aharony
- Department of Urology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
| | - Oleg Loutochin
- Department of Urology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
| | - Jacques Corcos
- Department of Urology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
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