TY - JOUR
T1 - Vascular bioengineering of scaffolds derived from human discarded transplant kidneys using human pluripotent stem cell-derived endothelium
AU - Leuning, Danielle G.
AU - Witjas, Franca M. R.
AU - Maanaoui, Mehdi
AU - de Graaf, Annemarie M. A.
AU - Lievers, Ellen
AU - Geuens, Thomas
AU - Avramut, Christina M.
AU - Wiersma, Loes E.
AU - van den Berg, Cathelijne W.
AU - Sol, Wendy M. P. J.
AU - de Boer, Hetty
AU - Wang, Gangqi
AU - LaPointe, Vanessa L. S.
AU - van der Vlag, Johan
AU - van Kooten, Cees
AU - van den Berg, Bernard M.
AU - Little, Melissa H.
AU - Engelse, Marten A.
AU - Rabelink, Ton J.
N1 - Funding Information:
The research leading to these results has received funding from the European Community's Seventh Framework Program (FP7/2007‐2013) under grant agreement number 305436 (STELLAR) and from the Dutch Kidney Foundation (RECORD KID, 15RN02). We would like to thank Valeria Orlova (department of anatomy and embryology, Leiden University Medical Center) for her help with the iPS‐EC differentiation technique. We also thank the Maastricht MultiModal Molecular Imaging Institute–Division of Imaging Mass Spectrometry for performing the mass spectrometry runs.
Funding Information:
The research leading to these results has received funding from the European Community's Seventh Framework Program (FP7/2007-2013) under grant agreement number 305436 (STELLAR) and from the Dutch Kidney Foundation (RECORD KID, 15RN02). We would like to thank Valeria Orlova (department of anatomy and embryology, Leiden University Medical Center) for her help with the iPS-EC differentiation technique. We also thank the Maastricht MultiModal Molecular Imaging Institute?Division of Imaging Mass Spectrometry for performing the mass spectrometry runs.
Publisher Copyright:
© 2018 The Authors American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons
PY - 2019/5
Y1 - 2019/5
N2 - 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.
AB - 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.
KW - basic (laboratory) research/science
KW - kidney transplantation/nephrology
KW - regenerative medicine
KW - stem cells
KW - tissue/organ engineering
KW - translational research/science
KW - vascular biology
KW - DECELLULARIZED RAT
KW - REGENERATION
KW - PERICYTES
KW - PROTEIN
U2 - 10.1111/ajt.15200
DO - 10.1111/ajt.15200
M3 - Article
C2 - 30506641
SN - 1600-6135
VL - 19
SP - 1328
EP - 1343
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 5
ER -