An organ-derived extracellular matrix triggers in situ kidney regeneration in a preclinical model

Abstract

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.

Mesenchymal stem cells-derived extracellular vesicles protect against oxidative stress-induced xenogeneic biological root injury via adaptive regulation of the PI3K/Akt/NRF2 pathway

“…The extracellular matrix (ECM) is a tissue-specific 3D network of fibrillar proteins, proteoglycans, and glycosaminoglycans that provides cells and tissues with spatial communication signals, structural and ductile properties, and a medium for the transport and movement of nutrients and oxygen [ 1 – 3 ]. Owing to the limited donor pool of human-derived ECM, xenogeneic ECM (xECM) is currently being studied for application in tissue and organ regeneration [ 5 , 6 ]. Porcine tooth-derived dentin matrix, a type of xECM with a histological structure and bioactive factors comparable to those of human-derived dentin matrix, can promote odontogenesis and biomineralization [ 7 ].…”

A Multifunctional Acoustic Tweezer for Heterogenous Assembloids Patterning

“…In humans, the kidney comprises ≈750 000–2 000 000 nephrons. [ 40 ] Therefore, damage to a certain percentage of nephrons causes loss of kidney functions, such as a reduced glomerular filtration rate below 90%, which can increase urinary albumin excretion. [ 41 ] Thus, chronic kidney diseases progress from a filtration rate in the range of 30%–60% to end‐stage renal diseases at a filtration rate in the range of 15%–30% ( Figure a).…”

Post COVID-19 hyperinflammatory acute kidney injury and background ovarian insufficiency: Renal functional restoration after combined angiotensin-converting enzyme inhibitor with estrogen replacement

“…MicroRNA-93 inhibits the Wnt/β-catenin pathway, targeting Transcription factor 4 (TCF4) with improved renal function by reducing vascular calci cation [33]. While nephrons-like oocytes-are not believed to retain a replenishment capacity in adult mammals, in situ regrowth of nephrons has been observed in an animal model and speci c expression of SALL1 was observed among markers promoting this regeneration [34]. The role of ACE-inhibitors in managing renal disease is well established [5] and estradiol can also provide protection in acute injury [35].…”