|
1
|
Huang C, Yang Y, Li C, Guo L, Liu M, Xiong G. Benazepril Promotes the Proliferation and Differentiation of Urine-Derived Stem Cells from Children with Nephrotic Syndrome During the Chronic Kidney Disease Stage. Biochem Genet 2025:10.1007/s10528-025-11056-9. [PMID: 39969653 DOI: 10.1007/s10528-025-11056-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 02/07/2025] [Indexed: 02/20/2025]
Abstract
Nephrotic Syndrome (NS), especially in the Chronic Kidney Disease (CKD) stage, poses significant challenges in pediatric nephrology. Urine-derived stem cells (USCs) show promise for renal repair and regeneration. While benazepril is commonly used to treat CKD, its impact on USCs from children with NS during the CKD stage is unclear. USCs were isolated from the urine of 6 healthy children and 6 with NS (CKD stage), cultured through passages, and their morphology and cell surface markers were assessed microscopically and by flow cytometry, respectively. USCs were treated with benazepril at concentrations of 1, 10, 20, 40 μmol/L, and proliferation was evaluated using the CCK-8 assay. ROS levels were measured using DCFH-DA probe, and the expression levels of IL-1β, Connexin 43, AEC, ACE2, Ang2, AQP-1 and E-cadherin were analyzed by Western Blot. Tubular epithelial cell differentiation was also examined. USCs could be cultured from both healthy and NS (CKD stage) children, but USCs from NS children only reached passage 5 and exhibited weaker proliferation and differentiation abilities compared to those from healthy children. IL-1β, Connexin 43, ROS,ACE and Ang2 levels were higher in USCs from NS children than in those from healthy children, while ACE2 showed the opposite trend. Treatment with 1 μmol/L benazepril enhanced the proliferation and differentiation ability of USCs from NS children, inhibiting the level of inflammation factors, ROS, ACE and Ang2 while promoting ACE2 expression in these cells. This study offers valuable insights for future USCs applications.
Collapse
Affiliation(s)
- Chengqiang Huang
- Department of Pediatric Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361101, People's Republic of China
- Sichuan Clinical Research Center for Birth Defects, Luzhou, 646000, People's Republic of China
| | - Yuan Yang
- Department of Pediatric Surgery, The People's Hospital of Leshan, Sichuan Clinical Research Center for Birth Defects, Luzhou, 646000, People's Republic of China
| | - Cheng Li
- Department of Child Health Care, Children's Medical Center, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, People's Republic of China
| | - Ling Guo
- Department of Pediatric hematologic Oncology and Respiratory, Children's Medical Center, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, 646000, Sichuan, People's Republic of China
| | - Ming Liu
- Department of Pediatric Surgery, Children's Medical Center, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, 646000, Sichuan, People's Republic of China
| | - Geng Xiong
- Department of Pediatric Surgery, Children's Medical Center, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, 646000, Sichuan, People's Republic of China.
| |
Collapse
|
|
2
|
Elia E, Caneparo C, McMartin C, Chabaud S, Bolduc S. Tissue Engineering for Penile Reconstruction. Bioengineering (Basel) 2024; 11:230. [PMID: 38534504 DOI: 10.3390/bioengineering11030230] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 02/19/2024] [Accepted: 02/23/2024] [Indexed: 03/28/2024] Open
Abstract
The penis is a complex organ with a development cycle from the fetal stage to puberty. In addition, it may suffer from either congenital or acquired anomalies. Penile surgical reconstruction has been the center of interest for many researchers but is still challenging due to the complexity of its anatomy and functionality. In this review, penile anatomy, pathologies, and current treatments are described, including surgical techniques and tissue engineering approaches. The self-assembly technique currently applied is emphasized since it is considered promising for an adequate tissue-engineered penile reconstructed substitute.
Collapse
Affiliation(s)
- Elissa Elia
- Centre de Recherche en Organogénèse Expérimentale/LOEX, Regenerative Medicine Division, CHU de Québec-Université Laval Research Center, Québec, QC G1J 1Z4, Canada
| | - Christophe Caneparo
- Centre de Recherche en Organogénèse Expérimentale/LOEX, Regenerative Medicine Division, CHU de Québec-Université Laval Research Center, Québec, QC G1J 1Z4, Canada
| | - Catherine McMartin
- Division of Urology, Department of Surgery, CHU de Québec-Université Laval, Québec, QC G1V 4G2, Canada
| | - Stéphane Chabaud
- Centre de Recherche en Organogénèse Expérimentale/LOEX, Regenerative Medicine Division, CHU de Québec-Université Laval Research Center, Québec, QC G1J 1Z4, Canada
| | - Stéphane Bolduc
- Centre de Recherche en Organogénèse Expérimentale/LOEX, Regenerative Medicine Division, CHU de Québec-Université Laval Research Center, Québec, QC G1J 1Z4, Canada
- Division of Urology, Department of Surgery, CHU de Québec-Université Laval, Québec, QC G1V 4G2, Canada
| |
Collapse
|
|
3
|
Omidian H, Mfoafo K. Exploring the Potential of Nanotechnology in Pediatric Healthcare: Advances, Challenges, and Future Directions. Pharmaceutics 2023; 15:1583. [PMID: 37376032 DOI: 10.3390/pharmaceutics15061583] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 05/18/2023] [Accepted: 05/22/2023] [Indexed: 06/29/2023] Open
Abstract
The utilization of nanotechnology has brought about notable advancements in the field of pediatric medicine, providing novel approaches for drug delivery, disease diagnosis, and tissue engineering. Nanotechnology involves the manipulation of materials at the nanoscale, resulting in improved drug effectiveness and decreased toxicity. Numerous nanosystems, including nanoparticles, nanocapsules, and nanotubes, have been explored for their therapeutic potential in addressing pediatric diseases such as HIV, leukemia, and neuroblastoma. Nanotechnology has also shown promise in enhancing disease diagnosis accuracy, drug availability, and overcoming the blood-brain barrier obstacle in treating medulloblastoma. It is important to acknowledge that while nanotechnology offers significant opportunities, there are inherent risks and limitations associated with the use of nanoparticles. This review provides a comprehensive summary of the existing literature on nanotechnology in pediatric medicine, highlighting its potential to revolutionize pediatric healthcare while also recognizing the challenges and limitations that need to be addressed.
Collapse
Affiliation(s)
- Hossein Omidian
- College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA
| | - Kwadwo Mfoafo
- College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA
| |
Collapse
|
|
4
|
Patrício D, Santiago J, Mano JF, Fardilha M. Organoids of the male reproductive system: Challenges, opportunities, and their potential use in fertility research. WIREs Mech Dis 2023; 15:e1590. [PMID: 36442887 DOI: 10.1002/wsbm.1590] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 10/17/2022] [Accepted: 11/12/2022] [Indexed: 11/30/2022]
Abstract
Organoids are units of function of a given organ able to reproduce, in culture, a biological structure similar in architecture and function to its counterpart in vivo. Today, it is possible to develop an organoid from a fragment of tissue, a stem cell located in an adult organ, an embryonic stem cell, or an induced pluripotent stem cell. In the past decade, many organoids have been developed which mimic stomach, pancreas, liver and brain tissues, optic cups, among many others. Additionally, different male reproductive system organs have already been developed as organoids, including the prostate and testis. These 3D cultures may be of great importance for urological cancer research and have the potential to be used in fertility research for the study of spermatozoa production and maturation, germ cells-somatic cells interactions, and mechanisms of disease. They also provide an accurate preclinical pipeline for drug testing and discovery, as well as for the study of drug resistance. In this work, we revise the current knowledge on organoid technology and its use in healthcare and research, describe the male reproductive system organoids and other biomaterials already developed, and discuss their current application. Finally, we highlight the research gaps, challenges, and opportunities in the field and propose strategies to improve the use of organoids for the study of male infertility situations. This article is categorized under: Reproductive System Diseases > Stem Cells and Development Reproductive System Diseases > Biomedical Engineering.
Collapse
Affiliation(s)
- Daniela Patrício
- Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal.,Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, Aveiro, Portugal
| | - Joana Santiago
- Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
| | - João F Mano
- Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, Aveiro, Portugal
| | - Margarida Fardilha
- Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
| |
Collapse
|
|
5
|
Prospects and Challenges of Electrospun Cell and Drug Delivery Vehicles to Correct Urethral Stricture. Int J Mol Sci 2022; 23:ijms231810519. [PMID: 36142432 PMCID: PMC9502833 DOI: 10.3390/ijms231810519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 08/30/2022] [Accepted: 09/01/2022] [Indexed: 11/17/2022] Open
Abstract
Current therapeutic modalities to treat urethral strictures are associated with several challenges and shortcomings. Therefore, significant strides have been made to develop strategies with minimal side effects and the highest therapeutic potential. In this framework, electrospun scaffolds incorporated with various cells or bioactive agents have provided promising vistas to repair urethral defects. Due to the biomimetic nature of these constructs, they can efficiently mimic the native cells’ niches and provide essential microenvironmental cues for the safe transplantation of multiple cell types. Furthermore, these scaffolds are versatile platforms for delivering various drug molecules, growth factors, and nucleic acids. This review discusses the recent progress, applications, and challenges of electrospun scaffolds to deliver cells or bioactive agents during the urethral defect repair process. First, the current status of electrospinning in urethral tissue engineering is presented. Then, the principles of electrospinning in drug and cell delivery applications are reviewed. Finally, the recent preclinical studies are summarized and the current challenges are discussed.
Collapse
|
|
6
|
Fang J, Peng T, Liu J, Liu H, Liu T, Zhang Z, Zhao C, Li Y, Wang Q, Chen H, Li T, Huang S, Pu X. Muscle-derived Stem Cells Combined With Nerve Growth Factor Transplantation in the Treatment of Stress Urinary Incontinence. Urology 2022; 166:126-132. [PMID: 35490902 DOI: 10.1016/j.urology.2022.04.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 04/08/2022] [Accepted: 04/11/2022] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To investigate the efficacy of muscle-derived stem cells (MDSCs) combined with nerve growth factor (NGF) in the treatment of stress urinary incontinence (SUI) METHODS: MDSCs were isolated and extracted from 90 SD rats, and the stem cell characteristics of the cells were identified using flow cytometry. NGF overexpression (oe-NGF) plasmid was coated with adenovirus and qRT-PCR was applied to verify adenovirus transfection efficiency. The rat models of SUI were constructed and randomly divided into 5 groups: control group, phosphate buffer (PBS) group, MDSCs + oe-NGF group, MDSCs + vector group, and MDSCs group. After 8 weeks of feeding, the leakage point pressure (LPP) rats, and Masson staining of rat urethral sections were detected. The expression of NGF and vascular endothelial growth factor (VEGF) was detected by western blot and IHC staining. RESULTS Compared with the control group, the LPP and the ratio of muscle fibers/collagen fibers were significantly increased in the MDSCs treated groups, with the highest increase in the MDSCs + oe-NGF group. Western blot and IHC results showed that the expression of NGF and VEGF in the urethral tissues in the MDSCs treated groups were significantly up-regulated comparing with the control group, with the highest increase in the MDSCs + oe-NGF group. CONCLUSION MDSCs alone can relieve SUI, while MDSCs combined with NGF is more effective, which may be related to the up-regulating of VEGF.
Collapse
Affiliation(s)
- Jianxiong Fang
- Department of Urology, Jiangmen Central Hospital, Jiangmen, PR China; Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, PR China
| | - Tianming Peng
- Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, PR China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou, PR China
| | - Jiumin Liu
- Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, PR China
| | - Haosheng Liu
- Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, PR China
| | - Tianqi Liu
- Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, PR China; Shantou University Medical College, Shantou, PR China
| | - Zhenhui Zhang
- Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, PR China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou, PR China
| | - Chao Zhao
- Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, PR China
| | - Yong Li
- Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, PR China
| | - Qianqian Wang
- Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, PR China
| | - Hanzhong Chen
- Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, PR China
| | - Teng Li
- Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, PR China
| | - Shang Huang
- Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, PR China
| | - Xiaoyong Pu
- Department of Urology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, PR China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou, PR China.
| |
Collapse
|
|
7
|
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: 25] [Impact Index Per Article: 8.3] [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.
Collapse
|
|
8
|
Cell Technologies in the Stress Urinary Incontinence Correction. Biomedicines 2022; 10:biomedicines10020309. [PMID: 35203518 PMCID: PMC8869383 DOI: 10.3390/biomedicines10020309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 01/22/2022] [Accepted: 01/24/2022] [Indexed: 11/16/2022] Open
Abstract
The scientific literature of recent years contains a lot of data about using multipotent stromal cells (MSCs) for urinary incontinence correction. Despite this, the ideal treatment method for urinary incontinence has not yet been created. The cell therapy results in patients and experimental animals with incontinence have shown promising results, but the procedures require further optimization, and more research is needed to focus on the clinical phase. The MSC use appears to be a feasible, safe, and effective method of treatment for patients with urinary incontinence. However, the best mode for application of cell technology is still under study. Most clinical investigations have been performed on only a few patients and during rather short follow-up periods, which, together with an incomplete knowledge of the mechanisms of MSC action, does not make it possible for their widespread implementation. The technical details regarding the MSC application remain to be identified in more rigorous preclinical and clinical trials.
Collapse
|
|
9
|
Caneparo C, Sorroza-Martinez L, Chabaud S, Fradette J, Bolduc S. Considerations for the clinical use of stem cells in genitourinary regenerative medicine. World J Stem Cells 2021; 13:1480-1512. [PMID: 34786154 PMCID: PMC8567446 DOI: 10.4252/wjsc.v13.i10.1480] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 07/12/2021] [Accepted: 09/17/2021] [Indexed: 02/06/2023] Open
Abstract
The genitourinary tract can be affected by several pathologies which require repair or replacement to recover biological functions. Current therapeutic strategies are challenged by a growing shortage of adequate tissues. Therefore, new options must be considered for the treatment of patients, with the use of stem cells (SCs) being attractive. Two different strategies can be derived from stem cell use: Cell therapy and tissue therapy, mainly through tissue engineering. The recent advances using these approaches are described in this review, with a focus on stromal/mesenchymal cells found in adipose tissue. Indeed, the accessibility, high yield at harvest as well as anti-fibrotic, immunomodulatory and proangiogenic properties make adipose-derived stromal/SCs promising alternatives to the therapies currently offered to patients. Finally, an innovative technique allowing tissue reconstruction without exogenous material, the self-assembly approach, will be presented. Despite advances, more studies are needed to translate such approaches from the bench to clinics in urology. For the 21st century, cell and tissue therapies based on SCs are certainly the future of genitourinary regenerative medicine.
Collapse
Affiliation(s)
- Christophe Caneparo
- Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Centre de Recherche du CHU de Québec-Université Laval, Axe Médecine Régénératrice, Quebec G1J1Z4, Canada
| | - Luis Sorroza-Martinez
- Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Centre de Recherche du CHU de Québec-Université Laval, Axe Médecine Régénératrice, Quebec G1J1Z4, Canada
| | - Stéphane Chabaud
- Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Centre de Recherche du CHU de Québec-Université Laval, Axe Médecine Régénératrice, Quebec G1J1Z4, Canada
| | - Julie Fradette
- Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Centre de Recherche du CHU de Québec-Université Laval, Axe Médecine Régénératrice, Quebec G1J1Z4, Canada
- Department of Surgery, Faculty of Medicine, Université Laval, Quebec G1V0A6, Canada
| | - Stéphane Bolduc
- Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Centre de Recherche du CHU de Québec-Université Laval, Axe Médecine Régénératrice, Quebec G1J1Z4, Canada
- Department of Surgery, Faculty of Medicine, Université Laval, Quebec G1V0A6, Canada
| |
Collapse
|