TY - JOUR
T1 - An organ-derived extracellular matrix triggers in situ kidney regeneration in a preclinical model
AU - Tajima, Kazuki
AU - Yagi, Hiroshi
AU - Morisaku, Toshinori
AU - Nishi, Kotaro
AU - Kushige, Hiroko
AU - Kojima, Hideaki
AU - Higashi, Hisanobu
AU - Kuroda, Kohei
AU - Kitago, Minoru
AU - Adachi, Shungo
AU - Natsume, Tohru
AU - Nishimura, Kumiko
AU - Oya, Mototsugu
AU - Kitagawa, Yuko
N1 - Funding Information:
This study was supported by a grant from the Japan Agency for Medical Research and Development (AMED) (No. 21hm0102074h0003) awarded to H. Yagi and a Grant-in-Aid for Scientific Research (B) of the Japan Society for the Promotion of Science (JSPS) KAKENHI (No. 18H02875) awarded to H. Yagi. The JSR-Keio University Medical and Chemical Innovation Center (JKiC) also supported this study. The authors thank R. Kinoshita, N. Murakawa, M. Otomo, and M. Takahashi for technical laboratory support and T. Otake, K. Matsumoto, and K. Kumagai for assisting with the surgery and animal rearing during the experimental period.
Funding Information:
This study was supported by a grant from the Japan Agency for Medical Research and Development (AMED) (No. 21hm0102074h0003) awarded to H. Yagi and a Grant-in-Aid for Scientific Research (B) of the Japan Society for the Promotion of Science (JSPS) KAKENHI (No. 18H02875) awarded to H. Yagi. The JSR-Keio University Medical and Chemical Innovation Center (JKiC) also supported this study. The authors thank R. Kinoshita, N. Murakawa, M. Otomo, and M. Takahashi for technical laboratory support and T. Otake, K. Matsumoto, and K. Kumagai for assisting with the surgery and animal rearing during the experimental period.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - It has not been considered that nephrons regenerate in adult mammals. We present that an organ-derived extracellular matrix in situ induces nephron regeneration in a preclinical model. A porcine kidney-derived extracellular matrix was sutured onto the surface of partial nephrectomy (PN)-treated kidney. Twenty-eight days after implantation, glomeruli, vessels, and renal tubules, characteristic of nephrons, were histologically observed within the matrix. No fibrillogenesis was observed in the matrix nor the matrix-sutured kidney, although this occurred in a PN kidney without the matrix, indicating the structures were newly induced by the matrix. The expression of renal progenitor markers, including Sall1, Six2, and WT-1, within the matrix supported the induction of nephron regeneration by the matrix. Furthermore, active blood flow was observed inside the matrix using computed tomography. The matrix provides structural and functional foundations for the development of cell-free scaffolds with a remarkably low risk of immune rejection and cancerization.
AB - It has not been considered that nephrons regenerate in adult mammals. We present that an organ-derived extracellular matrix in situ induces nephron regeneration in a preclinical model. A porcine kidney-derived extracellular matrix was sutured onto the surface of partial nephrectomy (PN)-treated kidney. Twenty-eight days after implantation, glomeruli, vessels, and renal tubules, characteristic of nephrons, were histologically observed within the matrix. No fibrillogenesis was observed in the matrix nor the matrix-sutured kidney, although this occurred in a PN kidney without the matrix, indicating the structures were newly induced by the matrix. The expression of renal progenitor markers, including Sall1, Six2, and WT-1, within the matrix supported the induction of nephron regeneration by the matrix. Furthermore, active blood flow was observed inside the matrix using computed tomography. The matrix provides structural and functional foundations for the development of cell-free scaffolds with a remarkably low risk of immune rejection and cancerization.
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U2 - 10.1038/s41536-022-00213-y
DO - 10.1038/s41536-022-00213-y
M3 - Article
AN - SCOPUS:85125633575
SN - 2057-3995
VL - 7
JO - npj Regenerative Medicine
JF - npj Regenerative Medicine
IS - 1
M1 - 18
ER -