The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Rosalinde Masereeuw - One of the best experts on this subject based on the ideXlab platform.
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topographic guidance in melt electrowritten tubular scaffolds enhances engineered Kidney Tubule performance
Frontiers in Bioengineering and Biotechnology, 2021Co-Authors: Anne Metje Van Genderen, Katja Jansen, Jos Malda, Tina Vermonden, Jitske Jansen, Rosalinde Masereeuw, Marleen Kristen, Joost Van Duijn, Carl C L Schuurmans, Miguel CastilhoAbstract:Introduction: To date, tubular tissue engineering relies on large, non-porous tubular scaffolds (O > 2 mm) for mechanical self-support, or smaller (O 150-500 μm) tubes within bulk hydrogels for studying renal transport phenomena. To advance the engineering of Kidney Tubules for future implantation, constructs should be both self-supportive and yet small-sized and highly porous. Here, we hypothesize that the fabrication of small-sized porous tubular scaffolds with a highly organized fibrous microstructure by means of melt-electrowriting (MEW) allows the development of self-supported Kidney proximal Tubules with enhanced properties. Materials and Methods: A custom-built melt-electrowriting (MEW) device was used to fabricate tubular fibrous scaffolds with small diameter sizes (O = 0.5, 1, 3 mm) and well-defined, porous microarchitectures (rhombus, square, and random). Human umbilical vein endothelial cells (HUVEC) and human conditionally immortalized proximal tubular epithelial cells (ciPTEC) were seeded into the tubular scaffolds and tested for monolayer formation, integrity, and organization, as well as for extracellular matrix (ECM) production and renal transport functionality. Results: Tubular fibrous scaffolds were successfully manufactured by fine control of MEW instrument parameters. A minimum inner diameter of 1 mm and pore sizes of 0.2 mm were achieved and used for subsequent cell experiments. While HUVEC were unable to bridge the pores, ciPTEC formed tight monolayers in all scaffold microarchitectures tested. Well-defined rhombus-shaped pores outperformed and facilitated unidirectional cell orientation, increased collagen type IV deposition, and expression of the renal transporters and differentiation markers organic cation transporter 2 (OCT2) and P-glycoprotein (P-gp). Discussion and Conclusion: Here, we present smaller diameter engineered Kidney Tubules with microgeometry-directed cell functionality. Due to the well-organized tubular fiber scaffold microstructure, the tubes are mechanically self-supported, and the self-produced ECM constitutes the only barrier between the inner and outer compartment, facilitating rapid and active solute transport.
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spinach and chive for Kidney Tubule engineering the limitations of decellularized plant scaffolds and vasculature
Aaps Journal, 2021Co-Authors: Katja Jansen, Tina Vermonden, Jitske Jansen, Marianna Evangelopoulou, Carla Pou Casellas, Sarina Abrishamcar, Rosalinde MasereeuwAbstract:Tissue decellularization yields complex scaffolds with retained composition and structure, and plants offer an inexhaustible natural source of numerous shapes. Plant tissue could be a solution for regenerative organ replacement strategies and advanced in vitro modeling, as biofunctionalization of decellularized tissue allows adhesion of various kinds of human cells that can grow into functional tissue. Here, we investigated the potential of spinach leaf vasculature and chive stems for Kidney Tubule engineering to apply in tubular transport studies. We successfully decellularized both plant tissues and confirmed general scaffold suitability for topical recellularization with renal cells. However, due to anatomical restrictions, we believe that spinach and chive vasculature themselves cannot be recellularized by current methods. Moreover, gradual tissue disintegration and deficient diffusion capacity make decellularized plant scaffolds unsuitable for Kidney Tubule engineering, which relies on transepithelial solute exchange between two compartments. We conclude that plant-derived structures and biomaterials need to be carefully considered and possibly integrated with other tissue engineering technologies for enhanced capabilities.
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topographic guidance in melt electrowritten tubular scaffolds enhances engineered Kidney Tubule performance
Social Science Research Network, 2020Co-Authors: Anne Metje Van Genderen, Katja Jansen, Jos Malda, Tina Vermonden, Jitske Jansen, Rosalinde Masereeuw, Marleen Kristen, Joost Van Duijn, Carl C L Schuurmans, Miguel CastilhoAbstract:To advance the engineering of Kidney Tubules for future implantation, constructs should be both self-supportive and yet small-sized and highly porous. Here, we hypothesize that the fabrication of small-sized porous tubular scaffolds with a highly organized fibrous microstructure by means of melt-electrowriting (MEW) allows the development of self-supported Kidney proximal Tubules with enhanced properties. A custom-built MEW device was used to fabricate tubular fibrous scaffolds with small diameter sizes (O = 0.5, 1, 3 mm) and well-defined, porous microarchitectures (rhombus, square, and random). Human umbilical vein endothelial cells (HUVEC) and human conditionally immortalized proximal tubular epithelial cells (ciPTEC) were seeded into the scaffolds and tested for monolayer formation, integrity, and organization, as well as for extracellular matrix (ECM) production and renal transport functionality. Tubular scaffolds were successfully manufactured by fine control of MEW instrument parameters. A minimum inner diameter of 0.5 mm and pore sizes of 0.2 mm were achieved. CiPTEC formed tight monolayers in all scaffold microarchitectures tested, but well-defined rhombus-shaped pores outperformed and facilitated unidirectional cell orientation, increased collagen type IV deposition, and expression of the renal transporters and differentiation markers organic cation transporter 2 (OCT2) and P-glycoprotein (P-gp). To conclude, we present smaller diameter engineered Kidney Tubules with microgeometry-directed cell functionality. Due to the well-organized tubular fiber scaffold microstructure, the tubes are mechanically self-supported, and the self-produced ECM constitutes the only barrier between the inner and outer compartment, facilitating rapid and active solute transport.
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fabrication of Kidney proximal Tubule grafts using biofunctionalized electrospun polymer scaffolds
Macromolecular Bioscience, 2019Co-Authors: Katja Jansen, Miguel Castilho, Sanne Aarts, Michael M Kaminski, Soeren S Lienkamp, Roman Pichler, Jos Malda, Tina Vermonden, Jitske Jansen, Rosalinde MasereeuwAbstract:The increasing prevalence of end-stage renal disease and persistent shortage of donor organs call for alternative therapies for Kidney patients. Dialysis remains an inferior treatment as clearance of large and protein-bound waste products depends on active tubular secretion. Biofabricated tissues could make a valuable contribution, but Kidneys are highly intricate and multifunctional organs. Depending on the therapeutic objective, suitable cell sources and scaffolds must be selected. This study provides a proof-of-concept for stand-alone Kidney Tubule grafts with suitable mechanical properties for future implantation purposes. Porous tubular nanofiber scaffolds are fabricated by electrospinning 12%, 16%, and 20% poly-e-caprolactone (PCL) v/w (chloroform and dimethylformamide, 1:3) around 0.7 mm needle templates. The resulting scaffolds consist of 92%, 69%, and 54% nanofibers compared to microfibers, respectively. After biofunctionalization with L-3,4-dihydroxyphenylalanine and collagen IV, 10 × 106 proximal Tubule cells per mL are injected and cultured until experimental readout. A human-derived cell model can bridge all fiber-to-fiber distances to form a monolayer, whereas small-sized murine cells form monolayers on dense nanofiber meshes only. Fabricated constructs remain viable for at least 3 weeks and maintain functionality as shown by inhibitor-sensitive transport activity, which suggests clearance capacity for both negatively and positively charged solutes.
Michael G Shlipak - One of the best experts on this subject based on the ideXlab platform.
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the promise of Tubule biomarkers in Kidney disease a review
American Journal of Kidney Diseases, 2021Co-Authors: Michael G ShlipakAbstract:For over 70 years, serum creatinine has remained the primary index for detection and monitoring of Kidney disease. Tubulointerstitial damage and fibrosis are highly prognostic for subsequent Kidney failure in biopsy studies, yet this pathology is invisible to the clinician in the absence of a biopsy. Recent discovery of biomarkers that reflect distinct aspects of Kidney Tubule disease have led to investigations of whether these markers can provide additional information on risk of chronic Kidney disease (CKD) progression and associated adverse clinical end points, above and beyond estimated glomerular filtration rate and albuminuria. These biomarkers can be loosely grouped into those that mark Tubule cell injury (eg, Kidney injury molecule 1, monocyte chemoattractant protein 1) and those that mark Tubule cell dysfunction (eg, α1-microglobulin, uromodulin). These Kidney Tubule biomarkers provide new opportunities to monitor response to therapeutics used to treat CKD patients. In this review, we describe results from some unique contributions in this area and discuss the current challenges and requirements in the field to bring these markers to clinical practice. We advocate for a broader assessment of Kidney health that moves beyond a focus on the glomerulus, and we highlight how such tools can improve diagnostic accuracy and earlier assessment of therapeutic efficacy or harm in CKD patients.
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biomarkers of Kidney Tubule health ckd progression and acute Kidney injury in sprint systolic blood pressure intervention trial participants
American Journal of Kidney Diseases, 2021Co-Authors: Alexander L Bullen, Pranav S. Garimella, Alexandra K. Lee, Vasantha Jotwani, Michelle M Estrella, Ronit Katz, Michael G ShlipakAbstract:Rationale & objective SPRINT compared the effect of intensive versus standard systolic blood pressure targets on cardiovascular morbidity and mortality. In this ancillary study, we evaluated the use of exploratory factor analysis (EFA) to combine biomarkers of Kidney Tubule health in urine and plasma and then study their role in longitudinal eGFR change and risk of acute Kidney injury (AKI). Study design Observational cohort nested in a clinical trial. Setting & participants 2,351 SPRINT participants with eGFR Exposure(s) Levels of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), chitinase-3-like protein (YKL-40), Kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), alpha-1 microglobulin (α1m) and beta-2 microglobulin (β2m), uromodulin (UMOD), fibroblast growth factor-23 (FGF23), and intact parathyroid hormone (PTH). Outcome(s) Longitudinal changes in eGFR and risk of AKI. Analytical approach We performed EFA to capture different Tubule pathophysiologic processes. We used linear mixed effects models to evaluate the association of each factor with longitudinal changes in eGFR. We evaluated the association of the tubular factors scores with AKI using Cox proportional hazards regression. Results From ten biomarkers, EFA generated four factors reflecting Tubule injury/repair (NGAL, IL-18 and YKL-40), Tubule injury/fibrosis (KIM-1 and MCP-1), Tubule reabsorption (α1m and β2m), and Tubule reserve/mineral metabolism (UMOD, FGF23, and PTH). Each SD higher Tubule reserve/mineral metabolism factor scores were associated with a 0.58% (0.39%, 0.67%) faster eGFR decline independent of baseline eGFR and albuminuria. Both the Tubule injury/repair (HR per SD higher 1.18 [1.10, 1.37]) and Tubule injury/fibrosis factors (HR 1.23 [1.02, 1.48]) were independently associated with future risk of AKI. Limitations The factors require validation in other settings. Conclusions EFA allows parsimonious subgrouping of biomarkers into factors which are differentially associated with progressive eGFR decline and AKI. These subgroups may provide insights into the pathological processes driving adverse Kidney outcomes.
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association of urine biomarkers of Kidney Tubule injury and dysfunction with frailty index and cognitive function in persons with ckd in sprint
American Journal of Kidney Diseases, 2021Co-Authors: Lindsay M Miller, Alexandra K. Lee, Dena E Rifkin, Manjula Kurella Tamura, Nicholas M Pajewski, Daniel E Weiner, Tala Alrousan, Michael G ShlipakAbstract:Rationale & Objective The associations of the glomerular markers of Kidney disease, estimated glomerular filtration rate (eGFR) and albuminuria, with frailty and cognition are well established. However, the relationship of Kidney Tubule injury and dysfunction with frailty and cognition is unknown. Study Design Observational cross-sectional study. Setting & Participants 2,253 participants with eGFR Exposure Eight urine biomarkers: interleukin 18 (IL-18), Kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), chitinase-3-like protein 1 (YKL-40), monocyte chemoattractant protein 1 (MCP-1), α1-microglobulin (A1M), β2-microglobulin (B2M), and uromodulin (Umod). Outcome Frailty was measured using a previously validated frailty index (FI), categorized as fit (FI ≤ 0.10), less fit (0.10 0.21). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Analytical Approach Associations between Kidney Tubule biomarkers with categorical FI were evaluated using multinomial logistic regression with the fit group as the reference. Cognitive function was evaluated using linear regression. Models were adjusted for demographic, behavioral, and clinical variables including eGFR and urine albumin. Results Three of the 8 urine biomarkers of Tubule injury and dysfunction were independently associated with FI. Each 2-fold higher level of urine KIM-1, a marker of Tubule injury, was associated with a 1.22 (95% CI, 1.01-1.49) greater odds of being in the frail group. MCP-1, a marker of tubulointerstitial fibrosis, was associated with a 1.30 (95% CI, 1.04-1.64) greater odds of being in the frail group, and A1M, a marker of Tubule reabsorptive capacity, was associated with a 1.48 (95% CI, 1.11-1.96) greater odds of being in the frail group. These associations were independent of confounders including eGFR and urine albumin, and were stronger than those of urine albumin with FI (1.15 [95% CI, 0.99-1.34]). Higher urine B2M, another marker of Tubule reabsorptive capacity, was associated with worse cognitive scores at baseline (β: −0.09 [95% CI, −0.17 to −0.01]). Urine albumin was not associated with cognitive function. Limitations Cross-sectional design, and FI may not be generalizable in other populations. Conclusions Urine biomarkers of Tubule injury, fibrosis, and proximal Tubule reabsorptive capacity are variably associated with FI and worse cognition, independent of glomerular markers of Kidney health. Future studies are needed to validate these results among other patient populations.
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effects of intensive blood pressure lowering on Kidney Tubule injury in ckd a longitudinal subgroup analysis in sprint
American Journal of Kidney Diseases, 2019Co-Authors: Rakesh Malhotra, Walter T. Ambrosius, Alfred K. Cheung, Michel Chonchol, Timothy E. Craven, Anthony A. Killeen, William E Haley, Mark J Sarnak, Chirag R Parikh, Michael G ShlipakAbstract:Background Random assignment to the intensive systolic blood pressure (SBP) arm ( Study Design Longitudinal subgroup analysis of clinical trial participants. Settings & Participants Random sample of SPRINT participants with prevalent chronic Kidney disease (CKD) defined as eGFR Outcomes & Measurements Urine biomarkers of Tubule function (β2-microglobulin [B2M], α1-microglobulin [A1M]), and uromodulin), injury (interleukin 18, Kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin), inflammation (monocyte chemoattractant protein 1), and repair (human cartilage glycoprotein 40) at baseline, year 1, and year 4. Biomarkers were indexed to urine creatinine concentration and changes between arms were evaluated using mixed-effects linear models and an intention-to-treat approach. Results 978 SPRINT participants (519 in the intensive and 459 in the standard arm) with prevalent CKD were included. Mean age was 72±9 years and eGFR was 46.1±9.4mL/min/1.73m2 at baseline. Clinical characteristics, eGFR, urinary albumin-creatinine ratio, and all 8 biomarker values were similar across arms at baseline. Compared to the standard arm, eGFR was lower by 2.9 and 3.3mL/min/1.73m2 in the intensive arm at year 1 and year 4. None of the 8 Tubule marker levels was higher in the intensive arm compared to the standard arm at year 1 or year 4. Two Tubule function markers (B2M and A1M) were 29% (95% CI, 10%-43%) and 24% (95% CI, 10%-36%) lower at year 1 in the intensive versus standard arm, respectively. Limitations Exclusion of persons with diabetes, and few participants had advanced CKD. Conclusions Among participants with CKD in SPRINT, random assignment to the intensive SBP arm did not increase any levels of 8 urine biomarkers of Tubule cell damage despite loss of eGFR. These findings support the hypothesis that eGFR declines in the intensive arm of SPRINT predominantly reflect hemodynamic changes rather than intrinsic damage to Kidney Tubule cells.
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effect of intensive blood pressure lowering on Kidney Tubule injury findings from the accord trial study participants
American Journal of Kidney Diseases, 2019Co-Authors: Girish N Nadkarni, Michael G Shlipak, Chirag R Parikh, Kinsuk Chauhan, Veena Rao, Steven G CocaAbstract:Rationale & Objective Random assignment to intensive blood pressure (BP) lowering (systolic BP Study Design Longitudinal analysis of a subgroup of clinical trial participants. Settings & Participants A subgroup of 529 participants in ACCORD-BP. Exposures Urine biomarkers of tubular injury (Kidney injury molecule 1, interleukin 18 [IL-18]), repair (human cartilage glycoprotein 39 [YKL-40]), and inflammation (monocyte chemoattractant protein 1) at baseline and year 2. Outcomes Changes in eGFR from baseline to 2 years. Analytical Approach We compared changes in biomarker levels and eGFRs across participants treated to an intensive versus less intensive BP goal using analysis of covariance. Results Of 529 participants, 260 had been randomly assigned to the intensive and 269 to the standard BP arm. Mean age was 62±6.5 years and eGFR was 90mL/min/1.73m2. Baseline clinical characteristics, eGFRs, urinary albumin-creatinine ratios (ACRs), and urinary biomarker levels were similar across BP treatment groups. Compared to less intensive BP treatment, eGFR was 9.2mL/min/1.73m2 lower in the intensive BP treatment group at year 2. Despite the eGFR reduction, within this treatment group, ACR was 30% lower and 4 urinary biomarker levels were unchanged or lower at year 2. Also within this group, participants with the largest declines in eGFRs had greater reductions in urinary IL-18 and YKL-40 levels. In a subgroup analysis of participants developing incident chronic Kidney disease (sustained 30% decline and eGFR Limitations Few participants with advanced baseline chronic Kidney disease. Comparisons across treatment groups do not represent comparisons of treatment arms created solely through randomization. Conclusions Among a subset of ACCORD-BP trial participants, intensive BP control was associated with reductions in eGFRs, but not with an increase in injury marker levels. These findings support that eGFR decline observed with intensive BP goals in ACCORD participants may predominantly reflect hemodynamic alterations.
Katja Jansen - One of the best experts on this subject based on the ideXlab platform.
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topographic guidance in melt electrowritten tubular scaffolds enhances engineered Kidney Tubule performance
Frontiers in Bioengineering and Biotechnology, 2021Co-Authors: Anne Metje Van Genderen, Katja Jansen, Jos Malda, Tina Vermonden, Jitske Jansen, Rosalinde Masereeuw, Marleen Kristen, Joost Van Duijn, Carl C L Schuurmans, Miguel CastilhoAbstract:Introduction: To date, tubular tissue engineering relies on large, non-porous tubular scaffolds (O > 2 mm) for mechanical self-support, or smaller (O 150-500 μm) tubes within bulk hydrogels for studying renal transport phenomena. To advance the engineering of Kidney Tubules for future implantation, constructs should be both self-supportive and yet small-sized and highly porous. Here, we hypothesize that the fabrication of small-sized porous tubular scaffolds with a highly organized fibrous microstructure by means of melt-electrowriting (MEW) allows the development of self-supported Kidney proximal Tubules with enhanced properties. Materials and Methods: A custom-built melt-electrowriting (MEW) device was used to fabricate tubular fibrous scaffolds with small diameter sizes (O = 0.5, 1, 3 mm) and well-defined, porous microarchitectures (rhombus, square, and random). Human umbilical vein endothelial cells (HUVEC) and human conditionally immortalized proximal tubular epithelial cells (ciPTEC) were seeded into the tubular scaffolds and tested for monolayer formation, integrity, and organization, as well as for extracellular matrix (ECM) production and renal transport functionality. Results: Tubular fibrous scaffolds were successfully manufactured by fine control of MEW instrument parameters. A minimum inner diameter of 1 mm and pore sizes of 0.2 mm were achieved and used for subsequent cell experiments. While HUVEC were unable to bridge the pores, ciPTEC formed tight monolayers in all scaffold microarchitectures tested. Well-defined rhombus-shaped pores outperformed and facilitated unidirectional cell orientation, increased collagen type IV deposition, and expression of the renal transporters and differentiation markers organic cation transporter 2 (OCT2) and P-glycoprotein (P-gp). Discussion and Conclusion: Here, we present smaller diameter engineered Kidney Tubules with microgeometry-directed cell functionality. Due to the well-organized tubular fiber scaffold microstructure, the tubes are mechanically self-supported, and the self-produced ECM constitutes the only barrier between the inner and outer compartment, facilitating rapid and active solute transport.
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spinach and chive for Kidney Tubule engineering the limitations of decellularized plant scaffolds and vasculature
Aaps Journal, 2021Co-Authors: Katja Jansen, Tina Vermonden, Jitske Jansen, Marianna Evangelopoulou, Carla Pou Casellas, Sarina Abrishamcar, Rosalinde MasereeuwAbstract:Tissue decellularization yields complex scaffolds with retained composition and structure, and plants offer an inexhaustible natural source of numerous shapes. Plant tissue could be a solution for regenerative organ replacement strategies and advanced in vitro modeling, as biofunctionalization of decellularized tissue allows adhesion of various kinds of human cells that can grow into functional tissue. Here, we investigated the potential of spinach leaf vasculature and chive stems for Kidney Tubule engineering to apply in tubular transport studies. We successfully decellularized both plant tissues and confirmed general scaffold suitability for topical recellularization with renal cells. However, due to anatomical restrictions, we believe that spinach and chive vasculature themselves cannot be recellularized by current methods. Moreover, gradual tissue disintegration and deficient diffusion capacity make decellularized plant scaffolds unsuitable for Kidney Tubule engineering, which relies on transepithelial solute exchange between two compartments. We conclude that plant-derived structures and biomaterials need to be carefully considered and possibly integrated with other tissue engineering technologies for enhanced capabilities.
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topographic guidance in melt electrowritten tubular scaffolds enhances engineered Kidney Tubule performance
Social Science Research Network, 2020Co-Authors: Anne Metje Van Genderen, Katja Jansen, Jos Malda, Tina Vermonden, Jitske Jansen, Rosalinde Masereeuw, Marleen Kristen, Joost Van Duijn, Carl C L Schuurmans, Miguel CastilhoAbstract:To advance the engineering of Kidney Tubules for future implantation, constructs should be both self-supportive and yet small-sized and highly porous. Here, we hypothesize that the fabrication of small-sized porous tubular scaffolds with a highly organized fibrous microstructure by means of melt-electrowriting (MEW) allows the development of self-supported Kidney proximal Tubules with enhanced properties. A custom-built MEW device was used to fabricate tubular fibrous scaffolds with small diameter sizes (O = 0.5, 1, 3 mm) and well-defined, porous microarchitectures (rhombus, square, and random). Human umbilical vein endothelial cells (HUVEC) and human conditionally immortalized proximal tubular epithelial cells (ciPTEC) were seeded into the scaffolds and tested for monolayer formation, integrity, and organization, as well as for extracellular matrix (ECM) production and renal transport functionality. Tubular scaffolds were successfully manufactured by fine control of MEW instrument parameters. A minimum inner diameter of 0.5 mm and pore sizes of 0.2 mm were achieved. CiPTEC formed tight monolayers in all scaffold microarchitectures tested, but well-defined rhombus-shaped pores outperformed and facilitated unidirectional cell orientation, increased collagen type IV deposition, and expression of the renal transporters and differentiation markers organic cation transporter 2 (OCT2) and P-glycoprotein (P-gp). To conclude, we present smaller diameter engineered Kidney Tubules with microgeometry-directed cell functionality. Due to the well-organized tubular fiber scaffold microstructure, the tubes are mechanically self-supported, and the self-produced ECM constitutes the only barrier between the inner and outer compartment, facilitating rapid and active solute transport.
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fabrication of Kidney proximal Tubule grafts using biofunctionalized electrospun polymer scaffolds
Macromolecular Bioscience, 2019Co-Authors: Katja Jansen, Miguel Castilho, Sanne Aarts, Michael M Kaminski, Soeren S Lienkamp, Roman Pichler, Jos Malda, Tina Vermonden, Jitske Jansen, Rosalinde MasereeuwAbstract:The increasing prevalence of end-stage renal disease and persistent shortage of donor organs call for alternative therapies for Kidney patients. Dialysis remains an inferior treatment as clearance of large and protein-bound waste products depends on active tubular secretion. Biofabricated tissues could make a valuable contribution, but Kidneys are highly intricate and multifunctional organs. Depending on the therapeutic objective, suitable cell sources and scaffolds must be selected. This study provides a proof-of-concept for stand-alone Kidney Tubule grafts with suitable mechanical properties for future implantation purposes. Porous tubular nanofiber scaffolds are fabricated by electrospinning 12%, 16%, and 20% poly-e-caprolactone (PCL) v/w (chloroform and dimethylformamide, 1:3) around 0.7 mm needle templates. The resulting scaffolds consist of 92%, 69%, and 54% nanofibers compared to microfibers, respectively. After biofunctionalization with L-3,4-dihydroxyphenylalanine and collagen IV, 10 × 106 proximal Tubule cells per mL are injected and cultured until experimental readout. A human-derived cell model can bridge all fiber-to-fiber distances to form a monolayer, whereas small-sized murine cells form monolayers on dense nanofiber meshes only. Fabricated constructs remain viable for at least 3 weeks and maintain functionality as shown by inhibitor-sensitive transport activity, which suggests clearance capacity for both negatively and positively charged solutes.
Jitske Jansen - One of the best experts on this subject based on the ideXlab platform.
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topographic guidance in melt electrowritten tubular scaffolds enhances engineered Kidney Tubule performance
Frontiers in Bioengineering and Biotechnology, 2021Co-Authors: Anne Metje Van Genderen, Katja Jansen, Jos Malda, Tina Vermonden, Jitske Jansen, Rosalinde Masereeuw, Marleen Kristen, Joost Van Duijn, Carl C L Schuurmans, Miguel CastilhoAbstract:Introduction: To date, tubular tissue engineering relies on large, non-porous tubular scaffolds (O > 2 mm) for mechanical self-support, or smaller (O 150-500 μm) tubes within bulk hydrogels for studying renal transport phenomena. To advance the engineering of Kidney Tubules for future implantation, constructs should be both self-supportive and yet small-sized and highly porous. Here, we hypothesize that the fabrication of small-sized porous tubular scaffolds with a highly organized fibrous microstructure by means of melt-electrowriting (MEW) allows the development of self-supported Kidney proximal Tubules with enhanced properties. Materials and Methods: A custom-built melt-electrowriting (MEW) device was used to fabricate tubular fibrous scaffolds with small diameter sizes (O = 0.5, 1, 3 mm) and well-defined, porous microarchitectures (rhombus, square, and random). Human umbilical vein endothelial cells (HUVEC) and human conditionally immortalized proximal tubular epithelial cells (ciPTEC) were seeded into the tubular scaffolds and tested for monolayer formation, integrity, and organization, as well as for extracellular matrix (ECM) production and renal transport functionality. Results: Tubular fibrous scaffolds were successfully manufactured by fine control of MEW instrument parameters. A minimum inner diameter of 1 mm and pore sizes of 0.2 mm were achieved and used for subsequent cell experiments. While HUVEC were unable to bridge the pores, ciPTEC formed tight monolayers in all scaffold microarchitectures tested. Well-defined rhombus-shaped pores outperformed and facilitated unidirectional cell orientation, increased collagen type IV deposition, and expression of the renal transporters and differentiation markers organic cation transporter 2 (OCT2) and P-glycoprotein (P-gp). Discussion and Conclusion: Here, we present smaller diameter engineered Kidney Tubules with microgeometry-directed cell functionality. Due to the well-organized tubular fiber scaffold microstructure, the tubes are mechanically self-supported, and the self-produced ECM constitutes the only barrier between the inner and outer compartment, facilitating rapid and active solute transport.
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spinach and chive for Kidney Tubule engineering the limitations of decellularized plant scaffolds and vasculature
Aaps Journal, 2021Co-Authors: Katja Jansen, Tina Vermonden, Jitske Jansen, Marianna Evangelopoulou, Carla Pou Casellas, Sarina Abrishamcar, Rosalinde MasereeuwAbstract:Tissue decellularization yields complex scaffolds with retained composition and structure, and plants offer an inexhaustible natural source of numerous shapes. Plant tissue could be a solution for regenerative organ replacement strategies and advanced in vitro modeling, as biofunctionalization of decellularized tissue allows adhesion of various kinds of human cells that can grow into functional tissue. Here, we investigated the potential of spinach leaf vasculature and chive stems for Kidney Tubule engineering to apply in tubular transport studies. We successfully decellularized both plant tissues and confirmed general scaffold suitability for topical recellularization with renal cells. However, due to anatomical restrictions, we believe that spinach and chive vasculature themselves cannot be recellularized by current methods. Moreover, gradual tissue disintegration and deficient diffusion capacity make decellularized plant scaffolds unsuitable for Kidney Tubule engineering, which relies on transepithelial solute exchange between two compartments. We conclude that plant-derived structures and biomaterials need to be carefully considered and possibly integrated with other tissue engineering technologies for enhanced capabilities.
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topographic guidance in melt electrowritten tubular scaffolds enhances engineered Kidney Tubule performance
Social Science Research Network, 2020Co-Authors: Anne Metje Van Genderen, Katja Jansen, Jos Malda, Tina Vermonden, Jitske Jansen, Rosalinde Masereeuw, Marleen Kristen, Joost Van Duijn, Carl C L Schuurmans, Miguel CastilhoAbstract:To advance the engineering of Kidney Tubules for future implantation, constructs should be both self-supportive and yet small-sized and highly porous. Here, we hypothesize that the fabrication of small-sized porous tubular scaffolds with a highly organized fibrous microstructure by means of melt-electrowriting (MEW) allows the development of self-supported Kidney proximal Tubules with enhanced properties. A custom-built MEW device was used to fabricate tubular fibrous scaffolds with small diameter sizes (O = 0.5, 1, 3 mm) and well-defined, porous microarchitectures (rhombus, square, and random). Human umbilical vein endothelial cells (HUVEC) and human conditionally immortalized proximal tubular epithelial cells (ciPTEC) were seeded into the scaffolds and tested for monolayer formation, integrity, and organization, as well as for extracellular matrix (ECM) production and renal transport functionality. Tubular scaffolds were successfully manufactured by fine control of MEW instrument parameters. A minimum inner diameter of 0.5 mm and pore sizes of 0.2 mm were achieved. CiPTEC formed tight monolayers in all scaffold microarchitectures tested, but well-defined rhombus-shaped pores outperformed and facilitated unidirectional cell orientation, increased collagen type IV deposition, and expression of the renal transporters and differentiation markers organic cation transporter 2 (OCT2) and P-glycoprotein (P-gp). To conclude, we present smaller diameter engineered Kidney Tubules with microgeometry-directed cell functionality. Due to the well-organized tubular fiber scaffold microstructure, the tubes are mechanically self-supported, and the self-produced ECM constitutes the only barrier between the inner and outer compartment, facilitating rapid and active solute transport.
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fabrication of Kidney proximal Tubule grafts using biofunctionalized electrospun polymer scaffolds
Macromolecular Bioscience, 2019Co-Authors: Katja Jansen, Miguel Castilho, Sanne Aarts, Michael M Kaminski, Soeren S Lienkamp, Roman Pichler, Jos Malda, Tina Vermonden, Jitske Jansen, Rosalinde MasereeuwAbstract:The increasing prevalence of end-stage renal disease and persistent shortage of donor organs call for alternative therapies for Kidney patients. Dialysis remains an inferior treatment as clearance of large and protein-bound waste products depends on active tubular secretion. Biofabricated tissues could make a valuable contribution, but Kidneys are highly intricate and multifunctional organs. Depending on the therapeutic objective, suitable cell sources and scaffolds must be selected. This study provides a proof-of-concept for stand-alone Kidney Tubule grafts with suitable mechanical properties for future implantation purposes. Porous tubular nanofiber scaffolds are fabricated by electrospinning 12%, 16%, and 20% poly-e-caprolactone (PCL) v/w (chloroform and dimethylformamide, 1:3) around 0.7 mm needle templates. The resulting scaffolds consist of 92%, 69%, and 54% nanofibers compared to microfibers, respectively. After biofunctionalization with L-3,4-dihydroxyphenylalanine and collagen IV, 10 × 106 proximal Tubule cells per mL are injected and cultured until experimental readout. A human-derived cell model can bridge all fiber-to-fiber distances to form a monolayer, whereas small-sized murine cells form monolayers on dense nanofiber meshes only. Fabricated constructs remain viable for at least 3 weeks and maintain functionality as shown by inhibitor-sensitive transport activity, which suggests clearance capacity for both negatively and positively charged solutes.
Miguel Castilho - One of the best experts on this subject based on the ideXlab platform.
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topographic guidance in melt electrowritten tubular scaffolds enhances engineered Kidney Tubule performance
Frontiers in Bioengineering and Biotechnology, 2021Co-Authors: Anne Metje Van Genderen, Katja Jansen, Jos Malda, Tina Vermonden, Jitske Jansen, Rosalinde Masereeuw, Marleen Kristen, Joost Van Duijn, Carl C L Schuurmans, Miguel CastilhoAbstract:Introduction: To date, tubular tissue engineering relies on large, non-porous tubular scaffolds (O > 2 mm) for mechanical self-support, or smaller (O 150-500 μm) tubes within bulk hydrogels for studying renal transport phenomena. To advance the engineering of Kidney Tubules for future implantation, constructs should be both self-supportive and yet small-sized and highly porous. Here, we hypothesize that the fabrication of small-sized porous tubular scaffolds with a highly organized fibrous microstructure by means of melt-electrowriting (MEW) allows the development of self-supported Kidney proximal Tubules with enhanced properties. Materials and Methods: A custom-built melt-electrowriting (MEW) device was used to fabricate tubular fibrous scaffolds with small diameter sizes (O = 0.5, 1, 3 mm) and well-defined, porous microarchitectures (rhombus, square, and random). Human umbilical vein endothelial cells (HUVEC) and human conditionally immortalized proximal tubular epithelial cells (ciPTEC) were seeded into the tubular scaffolds and tested for monolayer formation, integrity, and organization, as well as for extracellular matrix (ECM) production and renal transport functionality. Results: Tubular fibrous scaffolds were successfully manufactured by fine control of MEW instrument parameters. A minimum inner diameter of 1 mm and pore sizes of 0.2 mm were achieved and used for subsequent cell experiments. While HUVEC were unable to bridge the pores, ciPTEC formed tight monolayers in all scaffold microarchitectures tested. Well-defined rhombus-shaped pores outperformed and facilitated unidirectional cell orientation, increased collagen type IV deposition, and expression of the renal transporters and differentiation markers organic cation transporter 2 (OCT2) and P-glycoprotein (P-gp). Discussion and Conclusion: Here, we present smaller diameter engineered Kidney Tubules with microgeometry-directed cell functionality. Due to the well-organized tubular fiber scaffold microstructure, the tubes are mechanically self-supported, and the self-produced ECM constitutes the only barrier between the inner and outer compartment, facilitating rapid and active solute transport.
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topographic guidance in melt electrowritten tubular scaffolds enhances engineered Kidney Tubule performance
Social Science Research Network, 2020Co-Authors: Anne Metje Van Genderen, Katja Jansen, Jos Malda, Tina Vermonden, Jitske Jansen, Rosalinde Masereeuw, Marleen Kristen, Joost Van Duijn, Carl C L Schuurmans, Miguel CastilhoAbstract:To advance the engineering of Kidney Tubules for future implantation, constructs should be both self-supportive and yet small-sized and highly porous. Here, we hypothesize that the fabrication of small-sized porous tubular scaffolds with a highly organized fibrous microstructure by means of melt-electrowriting (MEW) allows the development of self-supported Kidney proximal Tubules with enhanced properties. A custom-built MEW device was used to fabricate tubular fibrous scaffolds with small diameter sizes (O = 0.5, 1, 3 mm) and well-defined, porous microarchitectures (rhombus, square, and random). Human umbilical vein endothelial cells (HUVEC) and human conditionally immortalized proximal tubular epithelial cells (ciPTEC) were seeded into the scaffolds and tested for monolayer formation, integrity, and organization, as well as for extracellular matrix (ECM) production and renal transport functionality. Tubular scaffolds were successfully manufactured by fine control of MEW instrument parameters. A minimum inner diameter of 0.5 mm and pore sizes of 0.2 mm were achieved. CiPTEC formed tight monolayers in all scaffold microarchitectures tested, but well-defined rhombus-shaped pores outperformed and facilitated unidirectional cell orientation, increased collagen type IV deposition, and expression of the renal transporters and differentiation markers organic cation transporter 2 (OCT2) and P-glycoprotein (P-gp). To conclude, we present smaller diameter engineered Kidney Tubules with microgeometry-directed cell functionality. Due to the well-organized tubular fiber scaffold microstructure, the tubes are mechanically self-supported, and the self-produced ECM constitutes the only barrier between the inner and outer compartment, facilitating rapid and active solute transport.
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fabrication of Kidney proximal Tubule grafts using biofunctionalized electrospun polymer scaffolds
Macromolecular Bioscience, 2019Co-Authors: Katja Jansen, Miguel Castilho, Sanne Aarts, Michael M Kaminski, Soeren S Lienkamp, Roman Pichler, Jos Malda, Tina Vermonden, Jitske Jansen, Rosalinde MasereeuwAbstract:The increasing prevalence of end-stage renal disease and persistent shortage of donor organs call for alternative therapies for Kidney patients. Dialysis remains an inferior treatment as clearance of large and protein-bound waste products depends on active tubular secretion. Biofabricated tissues could make a valuable contribution, but Kidneys are highly intricate and multifunctional organs. Depending on the therapeutic objective, suitable cell sources and scaffolds must be selected. This study provides a proof-of-concept for stand-alone Kidney Tubule grafts with suitable mechanical properties for future implantation purposes. Porous tubular nanofiber scaffolds are fabricated by electrospinning 12%, 16%, and 20% poly-e-caprolactone (PCL) v/w (chloroform and dimethylformamide, 1:3) around 0.7 mm needle templates. The resulting scaffolds consist of 92%, 69%, and 54% nanofibers compared to microfibers, respectively. After biofunctionalization with L-3,4-dihydroxyphenylalanine and collagen IV, 10 × 106 proximal Tubule cells per mL are injected and cultured until experimental readout. A human-derived cell model can bridge all fiber-to-fiber distances to form a monolayer, whereas small-sized murine cells form monolayers on dense nanofiber meshes only. Fabricated constructs remain viable for at least 3 weeks and maintain functionality as shown by inhibitor-sensitive transport activity, which suggests clearance capacity for both negatively and positively charged solutes.
