Donor‐Derived Engineered Microvessels for Cardiovascular Risk Stratification of Patients with Kidney Failure

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.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Donor‐Derived Engineered Microvessels for Cardiovascular Risk Stratification of Patients with Kidney Failure ; day:07 ; month:01 ; year:2024 ; extent:11
Small ; (07.01.2024) (gesamt 11)

Creator
Rathod, Mitesh L.
Aw, Wen Yih
Huang, Stephanie
Lu, Jingming
Doherty, Elizabeth L.
Whithworth, Chloe P.
Xi, Gang
Roy‐Chaudhury, Prabir
Polacheck, William J.

DOI
10.1002/smll.202307901
URN
urn:nbn:de:101:1-2024010814213536531015
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
15.08.2025, 7:38 AM CEST

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Associated

  • Rathod, Mitesh L.
  • Aw, Wen Yih
  • Huang, Stephanie
  • Lu, Jingming
  • Doherty, Elizabeth L.
  • Whithworth, Chloe P.
  • Xi, Gang
  • Roy‐Chaudhury, Prabir
  • Polacheck, William J.

Other Objects (12)