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1.
BJU Int ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953550

RESUMO

OBJECTIVES: To evaluate the utility of the 17-gene Genomic Prostate Score® (GPS; MDxHealth, Irvine, CA, USA) performed on prostate cancer at the positive margin of the radical prostatectomy (RP) for its association with risk of subsequent biochemical recurrence (BCR). PATIENTS AND METHODS: We designed a case-cohort for the outcome of BCR, selecting 223 from a cohort of 813 RP patients treated at Johns Hopkins from 2008 to 2017 with positive margins and available clinical data; of these, 213 had available tissue and clinical data. RNA was isolated from formalin-fixed paraffin-embedded tumour tissue adjacent to the positive surgical margin and the GPS was evaluable in 203 of these patients with a score ranging from 0 to 100, with higher scores indicating higher risk. All patients underwent RP with or without adjuvant radiation therapy (ART). The statistical analysis employed Cox proportional hazards regression models for outcome of BCR weighted for case-cohort design. RESULTS: In univariable analysis, every 20-unit increase in the GPS was associated with a nearly threefold increase in risk of BCR (hazard ratio [HR] per 20 units 2.82, P < 0.001). In a multivariable Cox model adjusted for age, race, Cancer of the Prostate Risk Assessment Postsurgical score, Grade Group at the positive margin, and ART, the GPS was significantly associated with BCR (HR 1.56 per 20 units; 95% confidence interval 1.11-2.19; P = 0.011). The study is limited by its retrospective and single institution design. CONCLUSIONS: The GPS at the positive surgical margin could help stratify prognosis and inform clinical decision-making regarding adjuvant therapy after RP.

2.
Methods ; 171: 3-10, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31606388

RESUMO

The shortage of donor organs for transplantation remains a continued problem for patients with irreversible end-stage organ failure. Tissue engineering and regenerative medicine aims to develop therapies to provide viable solutions for these patients. Use of decellularized tissue scaffolds has emerged as an attractive approach to generate tissue constructs that mimic native tissue architecture and vascular networks. The process of decellularization which involves the removal of resident cellular components from donor tissues has been successfully translated to the clinic for applications in patients. However, transplantation of bioengineered solid organs using this approach remains a challenge as the process requires repopulating target cells to achieve functioning organs. This article presents a comprehensive overview of the methods used to achieve decellularization, the types of decellularizing agents, and the potential cell sources that could be used to achieve tissue function. Understanding the mechanism of action of the decellularizing agent and the processing methods will provide the optimal results for applications.


Assuntos
Matriz Extracelular/genética , Medicina Regenerativa/tendências , Engenharia Tecidual/tendências , Alicerces Teciduais/tendências , Matriz Extracelular/química , Humanos , Doadores de Tecidos
3.
Urology ; 132: 81-86, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31299328

RESUMO

OBJECTIVE: To assess the impact of multiple (2 or more) bladder hydrodistentions (HODs) on anesthetic bladder capacity (BC) in a large cohort of interstitial cystitis/bladder pain syndrome (IC/BPS) patients. Urinary HOD under anesthesia is a third line therapeutic approach used to treat patients with IC/BPS. There is some concern that performing multiple therapeutic HODs may be contraindicated due to the potential for contributing to a diminished BC over time. MATERIALS AND METHODS: This is a retrospective chart review of IC/BPS patients from a single institution who had undergone 2 or more bladder HOD procedures. Patient demographic and clinical data, including BC under anesthesia, were retrieved from patient charts for analysis. Least squares regression slopes of BC under anesthesia were calculated and used to estimate within-patient BC changes over time. RESULTS: Data from 168 patients (637 HOD procedures) were included for analysis. The average change in BC, 0.52 ± 8.33 mL/mo, was not significantly different from 0 (P= .42). Linear regression analyses did not identify any significant correlation between BC over time with: (1) age, (2) number of HODs, (3) frequency of HODs, (4) average BC, (5) length of time with an IC/BPS diagnosis, or (6) length of time during which the patient's BC was evaluated. Moreover, there was no difference in BC change over time in patients with and without Hunner's lesion (P = .86). CONCLUSION: Multiple therapeutic HODs, over several years, do not result in a significant change in BC in IC/BPS patients.


Assuntos
Anestesia , Cistite Intersticial/terapia , Modalidades de Fisioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistite Intersticial/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modalidades de Fisioterapia/efeitos adversos , Estudos Retrospectivos , Bexiga Urinária/fisiopatologia , Água , Adulto Jovem
4.
Int Urogynecol J ; 30(11): 1863-1870, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31254048

RESUMO

INTRODUCTION AND HYPOTHESIS: Low anesthetic bladder capacity has been shown to be a biomarker for bladder-centric interstitial cystitis/bladder pain syndrome (IC/BPS). The goal of this study was to determine if histopathological evidence from bladder biopsies supports anesthetic bladder capacity (BC) as a marker to distinguish a bladder-centric IC/BPS subtype. METHODS: From a review of our large IC/BPS cohort of patients undergoing hydrodistention, we identified a total of 41 patients with low BC (≤ 400 ml); an additional 41 consecutive patients with BC > 400 ml were selected as the comparator group. The original bladder mucosal biopsy pathology slides were re-reviewed by a single pathologist (blinded to patient information) using a standardized grading scale developed for this study. RESULTS: Histologically, the low BC subjects exhibited higher levels of acute inflammation (p = 0.0299), chronic inflammation (p = 0.0139), and erosion on microscopy (p = 0.0155); however, there was no significant difference in mast cell count between groups (p = 0.4431). There was no significant gender difference between the groups; female patients were the majority in both groups (low BC: 94.12%, non-low BC: 100%; p = 0.1246). Individuals in the low BC group were older (p < 0.0001), had a higher incidence of Hunner's lesions on cystoscopy (p < 0.0001), and had significantly higher scores, i.e., more bother symptoms, on two IC/BPS questionnaires (ICPI, p = 0.0154; ICSI, p = 0.0005). CONCLUSIONS: IC/BPS patients with low anesthetic bladder capacity have histological evidence of significantly more acute and chronic inflammation compared with patients with a non-low bladder capacity. These data provide additional evidence to support low bladder capacity as a marker of a distinct bladder-centric IC/BPS phenotype.


Assuntos
Cistite Intersticial/diagnóstico , Cistite Intersticial/fisiopatologia , Bexiga Urinária/patologia , Bexiga Urinária/fisiopatologia , Adulto , Idoso , Anestésicos/farmacologia , Cistite Intersticial/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Bexiga Urinária/efeitos dos fármacos
5.
Neurourol Urodyn ; 38 Suppl 4: S76-S83, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31099087

RESUMO

Stress urinary incontinence (SUI) is an age health-related issue that generates interest due to its considerable public health burden and the controversies surrounding treatment. It is highly prevalent affecting 30-40% of all women during their lifetime. Midurethral slings are the standard of gold standard treatment for female patients with SUI. They have excellent short-term cure rates; however, their efficacy tends to decrease over time and patients often report urinary incontinence recurrence. This paper addresses the applicability of regenerative medicine and tissue engineering for the treatment of SUI in female patients. Cell-based treatment with periurethral injection of autologous adipose or muscle-derived stem cells have been used for SUI; however, the cure rates and SUI recurrence at 1 year were 40% and 70%, respectively. Novel minimally invasive approaches, such as low-intensity extracorporeal shock wave therapies have shown promising results in SUI animal models. In addition, local injection of growth factors, chemokines, and specific antibodies have shown histological evidence of neoangiogenesis, nerve, and sphincter regeneration in rodents and nonhuman primates with SUI. The use of bioactive factors and proteins secreted by cells, which is called secretomes, have been recognized as key regulators of various mechanisms, such as immunomodulation, angiogenesis, inflammation, apoptosis, and tissue repair. Emerging therapies aiming to replace or restore tissues and organ functionality may improve the long-term efficacy and in the near future may represent the standard of care for the treatment of SUI.


Assuntos
Medicina Regenerativa , Engenharia Tecidual , Incontinência Urinária por Estresse/cirurgia , Animais , Feminino , Humanos , Qualidade de Vida , Slings Suburetrais , Uretra/cirurgia
6.
Urol Pract ; 6(4): 209-214, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37317475

RESUMO

INTRODUCTION: Flexible cystoscopy is routinely performed as an outpatient procedure. The use of disposable sheaths can increase cystoscope life span and reduce staff costs. The primary end point of this study was to evaluate procedure related discomfort and pain, physician maneuverability, residual bioburden and reprocessing time. The secondary end point was to analyze the cost-effectiveness of a flexible cystoscope with a disposable sheath compared to a standard flexible cystoscope. METHODS: This randomized clinical trial was performed with women older than 18 years, with intact cognition and 7 days antibiotic-free who were referred to outpatient clinic for cystoscopy. Patients underwent cystoscopy with a standard flexible cystoscope or flexible cystoscope with disposable sheath. Urinalysis and culture were performed before and 14 days after cystoscopy. Patients filled out a pain/discomfort visual analog scale. Physicians filled out a 5-point Likert scale for the elements of ease of insertion, manipulation, optical quality and overall use. Reprocessing time and costs were compared between both cystoscopes. RESULTS: A total of 60 patients were included in the study, comprised of 30 who underwent standard flexible cystoscopy and 30 who underwent flexible cystoscopy with a protective sheath. Patient discomfort/pain was equivalent in both groups. The Likert scores were similar except for ease of insertion, which was higher with protective sheaths (p <0.02). Protective sheaths were associated with lower reprocessing time and costs (p <0.001). CONCLUSIONS: The use of protective sheaths effectively reduced procedure and staff related costs without causing any additional patient discomfort or pain. The learning curve of the sheathed scope may explain the difference reported by physicians regarding the ease of insertion.

7.
Neurourol Urodyn ; 37(7): 2141-2150, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30168617

RESUMO

OBJECTIVE: Persistent urinary incontinence (UI) and/or erectile dysfunction (ED) occur in 30-50% of post-radical prostatectomy patients regardless of nerve sparing approaches. Identification of potential treatment options for these patients will require testing in an animal model that develops these chronic conditions. The objective was to characterize a nonhuman primate (NHP) model of persistent post-prostatectomy ED and UI and then test the feasibility of periurethral injection of the chemokine CXCL-12. METHODS: Ten adult male cynomolgus monkeys were used. Two were used for study of normal male nonhuman primate genitourinary anatomy. Five were used for measures of sexual behavior, peak intra-corporal pressure (ICP), abdominal leak point pressures (ALPP) 3 and 6-months post open radical prostatectomy (ORP). Three additional ORP animals received ultrasound-guided peri-urethral injection of chemokine CXCL12 6 weeks after ORP, and UI/ED evaluated for up to 3 months. RESULTS: The anatomy, innervation, and vascular supply to the prostate and surrounding tissues of these male NHPs are substantially similar to those of human beings. ORP resulted in complete removal of the prostate gland along with both neurovascular bundles and seminal vesicles while permitting stable restoration of vesico-urethral patency. ORP produced sustained (6 months) decreases in ALPP, ICP's, and sexual function. Transurethral injection of chemokine CXCL12 was feasible and had beneficial effects on erectile and urinary function. CONCLUSIONS: ORP in NHPs produced persistent erectile and urinary tract dysfunction. Periurethral injection of CXCL-12 was feasible and improved both urinary incontinence and erectile dysfunction and suggests that this model can be used to test new approaches for both conditions.


Assuntos
Disfunção Erétil/etiologia , Disfunção Erétil/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , Prostatectomia/efeitos adversos , Incontinência Urinária/etiologia , Incontinência Urinária/fisiopatologia , Animais , Quimiocina CXCL12/uso terapêutico , Modelos Animais de Doenças , Disfunção Erétil/tratamento farmacológico , Estudos de Viabilidade , Macaca fascicularis , Masculino , Pelve/anatomia & histologia , Complicações Pós-Operatórias/tratamento farmacológico , Comportamento Sexual Animal , Incontinência Urinária/tratamento farmacológico , Urodinâmica
8.
Acta Biomater ; 75: 226-234, 2018 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-29883813

RESUMO

Kidney transplantation is currently the only definitive solution for the treatment of end-stage renal disease (ESRD), however transplantation is severely limited by the shortage of available donor kidneys. Recent progress in whole organ engineering based on decellularization/recellularization techniques has enabled pre-clinical in vivo studies using small animal models; however, these in vivo studies have been limited to short-term assessments. We previously developed a decellularization system that effectively removes cellular components from porcine kidneys. While functional re-endothelialization on the porcine whole kidney scaffold was able to improve vascular patency, as compared to the kidney scaffold only, the duration of patency lasted only a few hours. In this study, we hypothesized that significant damage in the microvasculatures within the kidney scaffold resulted in the cessation of blood flow, and that thorough investigation is necessary to accurately evaluate the vascular integrity of the kidney scaffolds. Two decellularization protocols [sodium dodecyl sulfate (SDS) with DNase (SDS + DNase) or Triton X-100 with SDS (TRX + SDS)] were used to evaluate and optimize the levels of vascular integrity within the kidney scaffold. Results from vascular analysis studies using vascular corrosion casting and angiograms demonstrated that the TRX + SDS method was able to better maintain intact and functional microvascular architectures such as glomeruli within the acellular matrices than that by the SDS + DNase treatment. Importantly, in vitro blood perfusion of the re-endothelialized kidney construct revealed improved vascular function of the scaffold by TRX + SDS treatment compared with the SDS + DNase. Our results suggest that the optimized TRX + SDS decellularization method preserves kidney-specific microvasculatures and may contribute to long-term vascular patency following implantation. STATEMENT OF SIGNIFICANCE: Kidney transplantation is the only curative therapy for patients with end-stage renal disease (ESRD). However, in the United States, the supply of donor kidneys meets less than one-fifth of the demand; and those patients that receive a donor kidney need life-long immunosuppressive therapy to avoid organ rejection. In the last two decades, regenerative medicine and tissue engineering have emerged as an attractive alternative to overcome these limitations. In 2013, Song et al. published the first experimental orthotopic transplantation of a bioengineering kidney in rodents. In this study, they demonstrated evidences of kidney tissue regeneration and partial function restoration. Despite these initial promising results, there are still many challenges to achieve long-term blood perfusion without graft thrombosis. In this paper, we demonstrated that perfusion of detergents through the renal artery of porcine kidneys damages the glomeruli microarchitecture as well as peritubular capillaries. Modifying dynamic parameters such as flow rate, detergent concentration, and decellularization time, we were able to establish an optimized decellularization protocol with no evidences of disruption of glomeruli microarchitecture. As a proof of concept, we recellularized the kidney scaffolds with endothelial cells and in vitro perfused whole porcine blood successfully for 24 h with no evidences of thrombosis.


Assuntos
Vasos Sanguíneos/química , Rim/irrigação sanguínea , Rim/química , Alicerces Teciduais/química , Animais , Suínos
9.
J Endourol ; 32(S1): S105-S110, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29774819

RESUMO

Urinary incontinence (UI) is a common symptom affecting almost one-third of adult women. UI can occur because of hypermobility or intrinsic sphincter deficiency of the urethra. Regardless its etiology, it is associated with poor quality of life and most of the incontinent women develop symptoms such as anxiety, depression, and social isolation over time. The synthetic midurethral sling (MUS) was first introduced in 1995 and quickly became the gold standard treatment for women with stress UI because of intrinsic sphincter deficiency and/or urethral hypermobility. This session addresses the indications, preoperative preparation, surgical steps, postoperative care, and complications related to synthetic MUSs. Owing to the exponential increase in the prevalence of mesh-related complications, we also developed a rational evidence-based algorithm that will help urologists to diagnose and manage this specific subset of patients.


Assuntos
Slings Suburetrais , Uretra/cirurgia , Incontinência Urinária por Estresse/cirurgia , Incontinência Urinária/cirurgia , Adulto , Algoritmos , Medicina Baseada em Evidências , Feminino , Humanos , Posicionamento do Paciente , Período Pós-Operatório , Período Pré-Operatório , Qualidade de Vida , Doenças Uretrais/cirurgia
10.
Urology ; 117: 1-8, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29287975

RESUMO

Chronic non-stone-related hydronephrosis from supravesical or bladder dysfunction in adults is often detected incidentally. This study aims to review the literature regarding supravesical obstruction or bladder dysfunction leading to bilateral hydronephrosis in adults and to develop an algorithm to identify patients at risk of renal failure. Cross-sectional studies, retrospective and prospective cohorts, clinical trials, and systematic reviews from 1980 to 2017 were included. From 8115 articles screened, 39 met the inclusion criteria. Despite the lack of studies addressing this issue, this review brings up a rational evidence-based algorithm to diagnose and manage adults with bilateral hydronephrosis due to supravesical or bladder disease or dysfunction.


Assuntos
Algoritmos , Hidronefrose/etiologia , Doenças Ureterais/complicações , Doenças da Bexiga Urinária/complicações , Adulto , Humanos , Medição de Risco/métodos , Doenças Ureterais/etiologia , Doenças da Bexiga Urinária/fisiopatologia
11.
J Urol ; 198(2): 369-375, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28202356

RESUMO

PURPOSE: Interstitial cystitis/bladder pain syndrome presents a significant clinical challenge due to symptom heterogeneity and the myriad associated comorbid medical conditions. We recently reported that diminished bladder capacity may represent a specific interstitial cystitis/bladder pain syndrome subphenotype. The objective of this study was to investigate the relationship between anesthetic bladder capacity, and urological and nonurological clinical findings in a cohort of patients with interstitial cystitis/bladder pain syndrome who had undergone therapeutic urinary bladder hydrodistention. MATERIALS AND METHODS: This is a retrospective chart review of prospectively collected data on women diagnosed with interstitial cystitis/bladder pain syndrome between 2011 and 2015 who underwent bladder hydrodistention. Assessments in each patient included a detailed history and physical examination, ICPI (Interstitial Cystitis Problem Index), ICSI (Interstitial Cystitis Symptom Index) and PUF (Pelvic Pain and Urgency/Frequency Patient Symptom Scale). Bladder capacity was determined during bladder hydrodistention with the patient under general anesthesia. RESULTS: Mean age was 45.8 years and mean bladder capacity was 857 ml in the 110 enrolled patients. We found a significant inverse correlation between bladder capacity and scores on 3 gold standard interstitial cystitis/bladder pain syndrome metrics, including ICPI (p = 0.0014), ICSI (p = 0.0022) and PUF (p = 0.0009) as well as urination frequency (p = 0.0025). Women with higher bladder capacity were significantly more likely to report depression (p = 0.0059) and irritable bowel syndrome (p = 0.022). CONCLUSIONS: Low bladder capacity while under anesthesia was significantly associated with high symptom scores on 3 validated interstitial cystitis/bladder pain syndrome questionnaires as well as with urinary frequency. However, it was not associated with depression or other common systemic pain problems. These results suggest that low bladder capacity is a marker for a bladder centric manifestation of interstitial cystitis/bladder pain syndrome.


Assuntos
Cistite Intersticial/complicações , Cistite Intersticial/patologia , Dor Pélvica/etiologia , Bexiga Urinária/patologia , Complacência (Medida de Distensibilidade) , Feminino , Humanos , Pessoa de Meia-Idade , Tamanho do Órgão , Dor Pélvica/patologia , Estudos Retrospectivos , Fatores de Risco , Urina
12.
Sex Med ; 5(1): e54-e60, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28087237

RESUMO

INTRODUCTION: Urinary incontinence (UI) has been associated with negative effects on women's sexuality. Women's sexuality and sexual function are a complex issue, and the role of UI is not completely clear. AIM: To assess the impact of UI on female sexual function by comparing this population with a control group of continent women. METHODS: We performed a case-control study from August 2012 to September 2013. We evaluated continent and incontinent women (age range = 30-70 years) for their sexuality. MAIN OUTCOME MEASURES: All patients were evaluated by anamnesis, physical examination, and self-report quality-of-life questionnaires. In addition, incontinent women underwent a 1-hour pad test. Patients without sexual activity were evaluated for the role of UI in their sexual abstinence. Sexual abstinence was defined as the absence of sexual activity for more than 6 months. All sexually active women completed the self-report Sexuality Quotient-Female Version (SQ-F) questionnaire. RESULTS: A total of 356 women were included in the study (incontinent, n = 243; continent, n = 113). Sexual abstinence was found in 162 women (45%). Incontinent women presented a higher prevalence (P < .001) of sexual abstinence than their counterparts (129 [53%] and 33 [29.2%], respectively). Age, marital status, and UI were found to be isolated predictive factors for more sexual abstinence in incontinent women. Sexually active women (incontinent, n = 114; continent, n = 80) presented similar demographic data. Despite a similar frequency of sexual activity, incontinent women had less sexual desire, foreplay, harmony with a partner, sexual comfort, and sexual satisfaction than their counterparts. Women with greater urinary leakage during the 1-hour pad test (weight > 11 g) had the worst sexual function (SQ-F) score. CONCLUSION: Women with UI were more likely to be sexual abstinent than continent women. Furthermore, women with UI showed less sexual desire, sexual comfort, and sexual satisfaction than their counterparts despite having a similar frequency of sexual activity.

13.
Curr Urol Rep ; 17(9): 65, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27448146

RESUMO

INTRODUCTION: According to FDA, in 2010, approximately 300,000 women underwent surgical procedures in the USA to repair pelvic organ prolapse and approximately 260,000 underwent surgical procedures to repair stress urinary incontinence. From 560,000 surgeries, synthetic mesh was used in one out of three, and three out of four were performed transvaginally. The incorporation of mesh into pelvic organ prolapse repair has improved the long-term surgical anatomical outcomes and lower recurrence rates. However, vaginal mesh placement is associated with risks such as vaginal mesh erosion, exposure, and infection. OBJECTIVE: The main objectives of this study were to review the literature regarding vaginal mesh exposure and, based on the literature evidences, develop an algorithm to help urologists and gynecologists to promptly recognize the problem and treat it effectively with minimal additional morbidity. RESULTS: Diabetes mellitus, advanced age, smoking, concomitant hysterectomy, surgeon's experience, surgical technique, and proper training in pelvic organ reconstructive procedures have all been shown to be risk factors for vaginal mesh exposure. The clinical presentation of mesh exposure varies and the management depends upon the extent and location of exposure, associated patient bother, voiding complaints, and involvement of adjacent viscera if any. Once vaginal mesh exposure is diagnosed, it would be pragmatic to rule out simultaneous perforation/erosion into the bladder/urethra or bowel and associated collection if any. CONCLUSIONS: The exponential increase in the number of mesh-related complications is related mainly to a lack of surgeon's experience and proper training in reconstructive pelvic surgeries as well as availability of easy-to-handle kits. Despite improvements in short- and long-term outcomes since the introduction of mesh in pelvic surgeries, the incidence of post-operative complications remains elevated. We developed an algorithm to facilitate prompt recognition and treatment of vaginal mesh exposure aiming to help urologists and gynecologists to achieve better outcomes and success rates.


Assuntos
Telas Cirúrgicas/efeitos adversos , Vagina/cirurgia , Algoritmos , Feminino , Humanos , Prolapso de Órgão Pélvico/cirurgia , Complicações Pós-Operatórias/etiologia , Fatores de Risco
15.
Expert Rev Clin Immunol ; 12(2): 169-82, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26634874

RESUMO

Kidney transplantation (KT), as a modality of renal replacement therapy (RRT), has been shown to be both economically and functionally superior to dialysis for the treatment of end-stage renal disease (ESRD). Progress in KT is limited by two major barriers: a) a chronic and burgeoning shortage of transplantable organs and b) the need for chronic immunosuppression following transplantation. Although ground-breaking advances in transplant immunology have improved patient survival and graft durability, a new pathway of innovation is needed in order to overcome current obstacles. Regenerative medicine (RM) holds the potential to shift the paradigm in RRT, through organ bioengineering. Manufactured organs represent a potentially inexhaustible source of transplantable grafts that would bypass the need for immunosuppressive drugs by using autologous cells to repopulate extracellular matrix (ECM) scaffolds. This overview discusses the current status of renal transplantation while reviewing the most promising innovations in RM therapy as applied to RRT.


Assuntos
Bioengenharia/métodos , Falência Renal Crônica/terapia , Transplante de Rim/métodos , Medicina Regenerativa/métodos , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Humanos , Falência Renal Crônica/imunologia , Transplante de Células-Tronco/métodos , Doadores de Tecidos/classificação , Doadores de Tecidos/estatística & dados numéricos , Imunologia de Transplantes/imunologia
16.
Ann Surg ; 264(1): 169-79, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26649588

RESUMO

OBJECTIVES: Our study aims at producing acellular extracellular matrix scaffolds from the human pancreas (hpaECMs) as a first critical step toward the production of a new-generation, fully human-derived bioartificial endocrine pancreas. In this bioartificial endocrine pancreas, the hardware will be represented by hpaECMs, whereas the software will consist in the cellular compartment generated from patient's own cells. BACKGROUND: Extracellular matrix (ECM)-based scaffolds obtained through the decellularization of native organs have become the favored platform in the field of complex organ bioengineering. However, the paradigm is now switching from the porcine to the human model. METHODS: To achieve our goal, human pancreata were decellularized with Triton-based solution and thoroughly characterized. Primary endpoints were complete cell and DNA clearance, preservation of ECM components, growth factors and stiffness, ability to induce angiogenesis, conservation of the framework of the innate vasculature, and immunogenicity. Secondary endpoint was hpaECMs' ability to sustain growth and function of human islet and human primary pancreatic endothelial cells. RESULTS: Results show that hpaECMs can be successfully and consistently produced from human pancreata and maintain their innate molecular and spatial framework and stiffness, and vital growth factors. Importantly, hpaECMs inhibit human naïve CD4 T-cell expansion in response to polyclonal stimuli by inducing their apoptosis and promoting their conversion into regulatory T cells. hpaECMs are cytocompatible and supportive of representative pancreatic cell types. DISCUSSION: We, therefore, conclude that hpaECMs has the potential to become an ideal platform for investigations aiming at the manufacturing of a regenerative medicine-inspired bioartificial endocrine pancreas.


Assuntos
Matriz Extracelular/metabolismo , Pâncreas , Engenharia Tecidual , Alicerces Teciduais , Humanos , Ilhotas Pancreáticas/metabolismo , Organogênese , Pâncreas/metabolismo , Regeneração , Engenharia Tecidual/métodos
18.
Curr Diab Rep ; 15(10): 69, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26275443

RESUMO

Kidney transplantation for the treatment of chronic kidney disease has established outcome and quality of life. However, its implementation is severely limited by a chronic shortage of donor organs; consequently, most candidates remain on dialysis and on the waiting list while accruing further morbidity and mortality. Furthermore, those patients that do receive kidney transplants are committed to a life-long regimen of immunosuppressive drugs that also carry significant adverse risk profiles. The disciplines of tissue engineering and regenerative medicine have the potential to produce alternative therapies which circumvent the obstacles posed by organ shortage and immunorejection. This review paper describes some of the most promising tissue-engineering solutions currently under investigation for the treatment of acute and chronic kidney diseases. The various stem cell therapies, whole embryo transplantation, and bioengineering with ECM scaffolds are outlined and summarized.


Assuntos
Nefropatias/fisiopatologia , Nefropatias/cirurgia , Transplante de Rim , Engenharia Tecidual , Animais , Humanos , Medicina Regenerativa , Transplante de Células-Tronco , Células-Tronco
19.
Stem Cell Res Ther ; 6: 107, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-26028404

RESUMO

Irreversible end-stage organ failure represents one of the leading causes of death, and organ transplantation is currently the only curative solution. Donor organ shortage and adverse effects of immunosuppressive regimens are the major limiting factors for this definitive practice. Recent developments in bioengineering and regenerative medicine could provide a solid base for the future creation of implantable, bioengineered organs. Whole-organ detergent-perfusion protocols permit clinicians to gently remove all the cells and at the same time preserve the natural three-dimensional framework of the native organ. Several decellularized organs, including liver, kidney, and pancreas, have been created as a platform for further successful seeding. These scaffolds are composed of organ-specific extracellular matrix that contains growth factors important for cellular growth and function. Macro- and microvascular tree is entirely maintained and can be incorporated in the recipient's vascular system after the implant. This review will emphasize recent achievements in the whole-organ scaffolds and at the same time underline complications that the scientific community has to resolve before reaching a functional bioengineered organ.


Assuntos
Bioengenharia , Matriz Extracelular/metabolismo , Coração/fisiologia , Humanos , Rim/citologia , Rim/fisiologia , Fígado/citologia , Fígado/fisiologia , Pulmão/citologia , Pulmão/fisiologia , Miocárdio/citologia , Organoides/citologia , Organoides/transplante , Pâncreas/citologia , Pâncreas/fisiologia , Engenharia Tecidual , Alicerces Teciduais
20.
Transplantation ; 99(9): 1807-16, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26018349

RESUMO

BACKGROUND: Extracellular matrix (ECM) scaffolds, obtained through detergent-based decellularization of native kidneys, represent the most promising platform for investigations aiming at manufacturing kidneys for transplant purposes. We previously showed that decellularization of the human kidney yields renal ECM scaffolds (hrECMs) that maintain their basic molecular components, are cytocompatible, stimulate angiogenesis, and show an intact innate vasculature. However, evidence that the decellularization preserves glomerular morphometric characteristics, physiological parameters (pressures and resistances of the vasculature bed), and biological properties of the renal ECM, including retention of important growth factors (GFs), is still missing. METHODS: To address these issues, we studied the morphometry and resilience of hrECMs' native vasculature with resin casting at electronic microscopy and pulse-wave measurements, respectively. Moreover, we determined the fate of 40 critical GFs post decellularization with a glass chip-based multiplex enzyme-linked immunosorbent assay array and in vitro immunofluorescence. RESULTS: Our method preserves the 3-dimensional conformation of the native glomerulus. Resin casting and pulse-wave measurements, showed that hrECMs preserves the microvascular morphology and morphometry, and physiological function. Moreover, GFs including vascular endothelial growth factor and its receptors are retained within the matrices. CONCLUSIONS: Our results indicate that discarded human kidneys are a suitable source of renal scaffolds because they maintain a well-preserved structure and function of the vasculature, as well as GFs that are fundamental to achieve a satisfying recellularization of the scaffold in vivo due to their angiogenic properties.


Assuntos
Matriz Extracelular , Hemodinâmica , Peptídeos e Proteínas de Sinalização Intercelular/análise , Glomérulos Renais , Microvasos , Alicerces Teciduais , Molde por Corrosão , Matriz Extracelular/química , Matriz Extracelular/ultraestrutura , Humanos , Glomérulos Renais/irrigação sanguínea , Glomérulos Renais/química , Glomérulos Renais/citologia , Glomérulos Renais/ultraestrutura , Microscopia Eletrônica de Varredura , Microvasos/química , Microvasos/fisiologia , Microvasos/ultraestrutura , Perfusão , Análise Serial de Proteínas , Análise de Onda de Pulso , Receptores de Fatores de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/análise
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