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Donor-Derived Engineered Microvessels for Cardiovascular Risk Stratification of Patients with Kidney Failure.
Rathod, Mitesh L; Aw, Wen Yih; Huang, Stephanie; Lu, Jingming; Doherty, Elizabeth L; Whithworth, Chloe P; Xi, Gang; Roy-Chaudhury, Prabir; Polacheck, William J.
Afiliación
  • Rathod ML; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill and Raleigh, NC, 27599, 27695, USA.
  • Aw WY; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill and Raleigh, NC, 27599, 27695, USA.
  • Huang S; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill and Raleigh, NC, 27599, 27695, USA.
  • Lu J; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill and Raleigh, NC, 27599, 27695, USA.
  • Doherty EL; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill and Raleigh, NC, 27599, 27695, USA.
  • Whithworth CP; Department of Genetics, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27599, USA.
  • Xi G; UNC Kidney Centre, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Roy-Chaudhury P; UNC Kidney Centre, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Polacheck WJ; WG (Bill Hefner) Salisbury VA Medical Center, Salisbury, NC, 28144, USA.
Small ; 20(24): e2307901, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38185718
ABSTRACT
Cardiovascular disease is the cause of death in ≈50% of hemodialysis patients. Accumulation of uremic solutes in systemic circulation is thought to be a key driver of the endothelial dysfunction that underlies elevated cardiovascular events. A challenge in understanding the mechanisms relating chronic kidney disease to cardiovascular disease is the lack of in vitro models that allow screening of the effects of the uremic environment on the endothelium. Here, a method is described for microfabrication of human blood vessels from donor cells and perfused with donor serum. The resulting donor-derived microvessels are used to quantify vascular permeability, a hallmark of endothelial dysfunction, in response to serum spiked with pathophysiological levels of indoxyl sulfate, and in response to serum from patients with chronic kidney disease and from uremic pigs. The uremic environment has pronounced effects on microvascular integrity as demonstrated by irregular cell-cell junctions and increased permeability in comparison to cell culture media and healthy serum. Moreover, the engineered microvessels demonstrate an increase in sensitivity compared to traditional 2D assays. Thus, the devices and the methods presented here have the potential to be utilized to risk stratify and to direct personalized treatments for patients with chronic kidney disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Cardiovasculares / Microvasos Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Small Asunto de la revista: ENGENHARIA BIOMEDICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Cardiovasculares / Microvasos Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Small Asunto de la revista: ENGENHARIA BIOMEDICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania