Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• American journal of transplantation, 2019-05, Vol.19 (5), p.1328-1343

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. Human decellularized kidney scaffolds can be functionally re‐endothelialized using expanded human pluripotent stem cell–derived endothelial cells.