Vascular bioengineering of scaffolds derived from human discarded transplant kidneys using human pluripotent stem cell-derived endothelium

Danielle G. Leuning, Franca M. R. Witjas, Mehdi Maanaoui, Annemarie M. A. de Graaf, Ellen Lievers, Thomas Geuens, Christina M. Avramut, Loes E. Wiersma, Cathelijne W. van den Berg, Wendy M. P. J. Sol, Hetty de Boer, Gangqi Wang, Vanessa L. S. LaPointe, Johan van der Vlag, Cees van Kooten, Bernard M. van den Berg, Melissa H. Little, Marten A. Engelse, Ton J. Rabelink*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

24 Citations (Web of Science)

Abstract

The bioengineering of a replacement kidney has been proposed as an approach to address the growing shortage of donor kidneys for the treatment of chronic kidney disease. One approach being investigated is the recellularization of kidney scaffolds. In this study, we present several key advances toward successful re-endothelialization of whole kidney matrix scaffolds from both rodents and humans. Based on the presence of preserved glycosoaminoglycans within the decelullarized kidney scaffold, we show improved localization of delivered endothelial cells after preloading of the vascular matrix with vascular endothelial growth factor and angiopoietin 1. Using a novel simultaneous arteriovenous delivery system, we report the complete re-endothelialization of the kidney vasculature, including the glomerular and peritubular capillaries, using human inducible pluripotent stem cell - derived endothelial cells. Using this source of endothelial cells, it was possible to generate sufficient endothelial cells to recellularize an entire human kidney scaffold, achieving efficient cell delivery, adherence, and endothelial cell proliferation and survival. Moreover, human re-endothelialized scaffold could, in contrast to the non-re-endothelialized human scaffold, be fully perfused with whole blood. These major advances move the field closer to a human bioengineered kidney.

Original languageEnglish
Pages (from-to)1328-1343
Number of pages16
JournalAmerican Journal of Transplantation
Volume19
Issue number5
DOIs
Publication statusPublished - May 2019

Keywords

  • basic (laboratory) research/science
  • kidney transplantation/nephrology
  • regenerative medicine
  • stem cells
  • tissue/organ engineering
  • translational research/science
  • vascular biology
  • DECELLULARIZED RAT
  • REGENERATION
  • PERICYTES
  • PROTEIN

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