Production and implantation of renal extracellular matrix scaffolds from porcine kidneys as a platform for renal bioengineering investigations.
BACKGROUND
It is important to identify new sources of transplantable organs because of the critical shortage of donor organs. Tissue engineering holds the potential to address this issue through the implementation of decellularization-recellularization technology.


OBJECTIVE
To produce and examine acellular renal extracellular matrix (ECM) scaffolds as a platform for kidney bioengineering.


METHODS
Porcine kidneys were decellularized with distilled water and sodium dodecyl sulfate-based solution. After rinsing with buffer solution to remove the sodium dodecyl sulfate, the so-obtained renal ECM scaffolds were processed for vascular imaging, histology, and cell seeding to investigate the vascular patency, degree of decellularization, and scaffold biocompatibility in vitro. Four whole renal scaffolds were implanted in pigs to assess whether these constructs would sustain normal blood pressure and to determine their biocompatibility in vivo. Pigs were sacrificed after 2 weeks and the explanted scaffolds were processed for histology.


RESULTS
Renal ECM scaffolds were successfully produced from porcine kidneys. Scaffolds retained their essential ECM architecture and an intact vascular tree and allowed cell growth. On implantation, unseeded scaffolds were easily reperfused, sustained blood pressure, and were tolerated throughout the study period. No blood extravasation occurred. Pathology of explanted scaffolds showed maintenance of renal ultrastructure. Presence of inflammatory cells in the pericapsular region and complete thrombosis of the vascular tree were evident.


CONCLUSIONS
Our investigations show that pig kidneys can be successfully decellularized to produce renal ECM scaffolds. These scaffolds maintain their basic components, are biocompatible, and show intact, though thrombosed, vasculature.
Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA. gorlando@wakehealth.edu
Giuseppe
G
Orlando
Alan C
AC
Farney
Samy S
SS
Iskandar
Sayed-Hadi
SH
Mirmalek-Sani
David C
DC
Sullivan
Emma
E
Moran
Tamer
T
AbouShwareb
Paolo
P
De Coppi
Kathryn J
KJ
Wood
Robert J
RJ
Stratta
Anthony
A
Atala
James J
JJ
Yoo
Shay
S
Soker
D000818:Animals; D005109:Extracellular Matrix; D007668:Kidney; D013552:Swine; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds