An organ-derived extracellular matrix triggers in situ kidney regeneration in a preclinical model.
Journal
NPJ Regenerative medicine
ISSN: 2057-3995
Titre abrégé: NPJ Regen Med
Pays: United States
ID NLM: 101699846
Informations de publication
Date de publication:
28 Feb 2022
28 Feb 2022
Historique:
received:
29
09
2021
accepted:
07
02
2022
entrez:
1
3
2022
pubmed:
2
3
2022
medline:
2
3
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35228532
doi: 10.1038/s41536-022-00213-y
pii: 10.1038/s41536-022-00213-y
pmc: PMC8885654
doi:
Types de publication
Journal Article
Langues
eng
Pagination
18Subventions
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP20hm0102074
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 18H02875
Informations de copyright
© 2022. The Author(s).
Références
Bertram, J. F., Douglas-Denton, R. N., Diouf, B., Hughson, M. D. & Hoy, W. E. Human nephron number: implications for health and disease. Pediatr. Nephrol. 26, 1529–1533 (2011).
pubmed: 21604189
doi: 10.1007/s00467-011-1843-8
Keller, G., Zimmer, G., Mall, G., Ritz, E. & Amann, K. Nephron number in patients with primary hypertension. N. Engl. J. Med. 348, 101–108 (2003).
pubmed: 12519920
doi: 10.1056/NEJMoa020549
Saxen, L. & Sariola, H. Early organogenesis of the kidney. Pediatr. Nephrol. 1, 385–392 (1987).
pubmed: 3153305
doi: 10.1007/BF00849241
Diep, C. Q. et al. Identification of adult nephron progenitors capable of kidney regeneration in zebrafish. Nature 470, 95–100 (2011).
pubmed: 21270795
pmcid: 3170921
doi: 10.1038/nature09669
Jha, V. et al. Chronic kidney disease: global dimension and perspectives. Lancet 382, 260–272 (2013).
pubmed: 23727169
doi: 10.1016/S0140-6736(13)60687-X
Wolfe, R. A. et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N. Engl. J. Med. 341, 1725–1730 (1999).
pubmed: 10580071
doi: 10.1056/NEJM199912023412303
Song, J. J. et al. Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat. Med. 19, 646–651 (2013).
pubmed: 23584091
pmcid: 3650107
doi: 10.1038/nm.3154
Barkan, D., Green, J. E. & Chambers, A. F. Extracellular matrix: a gatekeeper in the transition from dormancy to metastatic growth. Eur. J. Cancer 46, 1181–1188 (2010).
pubmed: 20304630
pmcid: 2856784
doi: 10.1016/j.ejca.2010.02.027
Sellaro, T. L., Ravindra, A. K., Stolz, D. B. & Badylak, S. F. Maintenance of hepatic sinusoidal endothelial cell phenotype in vitro using organ-specific extracellular matrix scaffolds. Tissue Eng. 13, 2301–2310 (2007).
pubmed: 17561801
doi: 10.1089/ten.2006.0437
Nelson, C. M. & Bissell, M. J. Of extracellular matrix, scaffolds, and signaling: tissue architecture regulates development, homeostasis, and cancer. Annu. Rev. Cell Dev. Biol. 22, 287–309 (2006).
pubmed: 16824016
pmcid: 2933192
doi: 10.1146/annurev.cellbio.22.010305.104315
Badylak, S. F., Freytes, D. O. & Gilbert, T. W. Extracellular matrix as a biological scaffold material: Structure and function. Acta Biomater. 5, 1–13 (2009).
pubmed: 18938117
doi: 10.1016/j.actbio.2008.09.013
Uygun, B. E. et al. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat. Med. 16, 814–820 (2010).
pubmed: 20543851
pmcid: 2930603
doi: 10.1038/nm.2170
Kadota, Y. et al. Mesenchymal stem cells support hepatocyte function in engineered liver grafts. Organogenesis 10, 268–277 (2014).
pubmed: 24488046
pmcid: 4154962
doi: 10.4161/org.27879
Yagi, H. et al. Human-scale whole-organ bioengineering for liver transplantation: a regenerative medicine approach. Cell Transplant. 22, 231–242 (2013).
pubmed: 22943797
doi: 10.3727/096368912X654939
Katsuki, Y. et al. Endocrine pancreas engineered using porcine islets and partial pancreatic scaffolds. Pancreatology 16, 922–930 (2016).
pubmed: 27350058
doi: 10.1016/j.pan.2016.06.007
Bonandrini, B. et al. Recellularization of well-preserved acellular kidney scaffold using embryonic stem cells. Tissue Eng. Part A 20, 1486–1498 (2014).
pubmed: 24320825
pmcid: 4011423
doi: 10.1089/ten.tea.2013.0269
Ross, E. A. et al. Embryonic stem cells proliferate and differentiate when seeded into kidney scaffolds. J. Am. Soc. Nephrol. 20, 2338–2347 (2009).
pubmed: 19729441
pmcid: 2799178
doi: 10.1681/ASN.2008111196
Shimoda, H. et al. Decellularized liver scaffolds promote liver regeneration after partial hepatectomy. Sci. Rep. 9, 12543 (2019).
pubmed: 31467359
pmcid: 6715632
doi: 10.1038/s41598-019-48948-x
Ong, A. M. et al. Bipolar needle electrocautery for laparoscopic partial nephrectomy without renal vascular occlusion in a porcine model. Urology 62, 1144–1148 (2003).
pubmed: 14665379
doi: 10.1016/S0090-4295(03)00689-7
Gurtner, G. C., Werner, S., Barrandon, Y. & Longaker, M. T. Wound repair and regeneration. Nature 453, 314–321 (2008).
pubmed: 18480812
doi: 10.1038/nature07039
Anderson, J. M., Rodriguez, A. & Chang, D. T. Foreign body reaction to biomaterials. Semin. Immunol. 20, 86–100 (2008).
pubmed: 18162407
doi: 10.1016/j.smim.2007.11.004
Sadtler, K. et al. Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells. Science 352, 366–370 (2016).
pubmed: 27081073
pmcid: 4866509
doi: 10.1126/science.aad9272
Duffield, J. S. Cellular and molecular mechanisms in kidney fibrosis. J. Clin. Invest. 124, 2299–2306 (2014).
pubmed: 24892703
pmcid: 4038570
doi: 10.1172/JCI72267
Stone, R. C. et al. Epithelial-mesenchymal transition in tissue repair and fibrosis. Cell Tissue Res. 365, 495–506 (2016).
pubmed: 27461257
pmcid: 5011038
doi: 10.1007/s00441-016-2464-0
Yamashita, S., Maeshima, A. & Nojima, Y. Involvement of renal progenitor tubular cells in epitherial-to mesenchymal transition in fibrotic rat kidneys. J. Am. Soc. Nephrol. 16, 2044–2051 (2005).
pubmed: 15888566
doi: 10.1681/ASN.2004080681
Kriz, W., Kaissling, B. & Le Hir, M. Epithelial-mesenchymal transition (EMT) in kidney fibrosis: fact or fantazy? J. Clin. Invest. 121, 468–474 (2011).
pubmed: 21370523
pmcid: 3026733
doi: 10.1172/JCI44595
Wang, Z. et al. Vimentin expression is required for the development EMT-related renal fibrosis following unilateral ureteral obstruction in mice. Am. J. Physiol. Ren. Physiol. 315, F769–F780 (2018).
doi: 10.1152/ajprenal.00340.2017
Ronconi, E. et al. Regeneration of glomerular podocytes by human renal progenitors. J. Am. Soc. Nephrol. 20, 322–332 (2009).
pubmed: 19092120
pmcid: 2637058
doi: 10.1681/ASN.2008070709
Ichimura, K. et al. Three-dimensional architecture of podocytes revealed by block-face scanning electron microscopy. Sci. Rep. 5, 8993 (2015).
pubmed: 25759085
pmcid: 4355681
doi: 10.1038/srep08993
Romagnani, P., Lasagni, L. & Remuzzi, G. Renal progenitors: an evolutionary conserved strategy for kidney regeneration. Nat. Rev. Nephrol. 9, 137–146 (2013).
pubmed: 23338209
doi: 10.1038/nrneph.2012.290
Bussolati, B. et al. Isolation of renal progenitor cells from adult human kidney. Am. J. Pathol. 166, 545–555 (2005).
pubmed: 15681837
pmcid: 1602314
doi: 10.1016/S0002-9440(10)62276-6
Kitahara, H. et al. Heterotopic transplantation of a decellularized and recellularized whole porcine heart. Interact. Cardiovasc. Thorac. Surg. 22, 571–579 (2016).
pubmed: 26902852
pmcid: 4892160
doi: 10.1093/icvts/ivw022
Hussein, K. H. et al. Biocompatibility and hemocompatibility of efficiently decellularized whole porcine kidney for tissue engineering. J. Biomed. Mater. Res. A 106, 2034–2047 (2018).
pubmed: 29569325
doi: 10.1002/jbm.a.36407
Watt, F. M. & Huck, W. T. Role of the extracellular matrix in regulating stem cell fate. Nat. Rev. Mol. Cell Biol. 14, 467–473 (2013).
pubmed: 23839578
doi: 10.1038/nrm3620
Miner, J. H. Organogenesis of the kidney glomerulus: focus on the glomerular basement membrane. Organogenesis 7, 75–82 (2011).
pubmed: 21519194
pmcid: 3142441
doi: 10.4161/org.7.2.15275
Chen, Y. M., Kikkawa, Y. & Miner, J. H. A missense LAMB2 mutation causes congenital nephrotic syndrome by impairing laminin secretion. J. Am. Soc. Nephrol. 22, 849–858 (2011).
pubmed: 21511833
pmcid: 3083307
doi: 10.1681/ASN.2010060632
Suh, J. H., Jarad, G., VanDeVoorde, R. G. & Miner, J. H. Forced expression of laminin beta1 in podocytes prevents nephrotic syndrome in mice lacking laminin beta2, a model for Pierson syndrome. Proc. Natl Acad. Sci. U. S. A. 108, 15348–15353 (2011).
pubmed: 21876163
pmcid: 3174642
doi: 10.1073/pnas.1108269108
Kashtan, C. E. Alport syndromes: phenotypic heterogeneity of progressive hereditary nephritis. Pediatr. Nephrol. 14, 502–512 (2000).
pubmed: 10872195
doi: 10.1007/s004670050804
Eming, S. A., Martin, P. & Tomic-Canic, M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci. Transl. Med. 6, 265sr6 (2014).
pubmed: 25473038
pmcid: 4973620
doi: 10.1126/scitranslmed.3009337
Alexakis, C., Maxwell, P. & Bou-Gharios, G. Organ-specific collagen expression: implications for renal disease. Nephron Exp. Nephrol. 102, e71–e75 (2006).
pubmed: 16286786
doi: 10.1159/000089684
Genovese, F., Manresa, A. A., Leeming, D. J., Karsdal, M. A. & Boor, P. The extracellular matrix in the kidney: a source of novel non-invasive biomarkers of kidney fibrosis? Fibrogenes. Tissue Repair 7, 4 (2014).
doi: 10.1186/1755-1536-7-4
Chitra, P. S. et al. Growth Hormone Induces Transforming Growth Factor-Beta-Induced Protein in Podocytes: Implications for Podocyte Depletion and Proteinuria. J. Cell. Biochem. 116, 1947–1956 (2015).
pubmed: 25740786
doi: 10.1002/jcb.25150
Grahammer, F., Schell, C. & Huber, T. B. The podocyte slit diaphragm−from a thin grey line to a complex signalling hub. Nat. Rev. Nephrol. 9, 587–598 (2013).
pubmed: 23999399
doi: 10.1038/nrneph.2013.169
Nouwen, E. J., Dauwe, S., van der Biest, I. & De Broe, M. E. Stage- and segment-specific expression of cell-adhesion molecules N-CAM, A-CAM, and L-CAM in the kidney. Kidney Int. 44, 147–158 (1993).
pubmed: 8355456
doi: 10.1038/ki.1993.225
Georgas, K. et al. Use of dual section mRNA in situ hybridisation/immunohistochemistry to clarify gene expression patterns during the early stages of nephron development in the embryo and in the mature nephron of the adult mouse kidney. Histochem. Cell Biol. 130, 927–942 (2008).
pubmed: 18618131
doi: 10.1007/s00418-008-0454-3
Venkatachalam, M. A., Bernard, D. B., Donohoe, J. F. & Levinsky, N. G. Ischemic damage and repair in the rat proximal tubule: differences among the S1, S2, and S3 segments. Kidney Int. 14, 31–49 (1978).
pubmed: 682423
doi: 10.1038/ki.1978.87
Hartman, H. A., Lai, H. L. & Patterson, L. T. Cessation of renal morphogenesis in mice. Dev. Biol. 310, 379–387 (2007).
pubmed: 17826763
pmcid: 2075093
doi: 10.1016/j.ydbio.2007.08.021