Renal Tissue Engineering with Decellularized Rhesus Monkey Kidneys: Age-Related Differences

Abstract

New therapies for severely damaged kidneys are needed due to limited regenerative capacity and organ donor shortages. The goal of this study was to repopulate decellularized kidney sections in vitro and to determine the impact of donor age on recellularization. This was addressed by generating decellularized kidney scaffolds from fetal, juvenile, and adult rhesus monkey kidney sections using a procedure that removes cellular components while preserving the structural and functional properties of the native extracellular matrix (ECM). Kidney scaffolds were recellularized using explants from different age groups (fetal, juvenile, adult) and fetal renal cell fractions. Results showed vimentin + cytokeratin + calbindin + cell infiltration and organization around the scaffold ECM. The extent of cellular repopulation was greatest with scaffolds from the youngest donors, and with seeding of mixed fetal renal aggregates that formed tubular structures within the kidney scaffolds. These findings suggest that decellularized kidney sections from different age groups can be effectively repopulated with donor cells and the age of the donor is a critical factor in repopulation efficiency.

Three-dimensional scaffolds of fetal decellularized hearts exhibit enhanced potential to support cardiac cells in comparison to the adult

“…growth factors, cytokines and proteases), we developed a decellularization protocol allowing parallel decellularization of whole fetal hearts and adult LV explants, while assuring a reliable comparison between both microenvironments by eliminating differences inherent to the use of distinct procedures. The decellularization of adult organs, in contrast to fetal tissues [20,46,47], has been extensively reported [6,10].…”

Age associated communication between cells and matrix: a potential impact on stem cell-based tissue regeneration strategies

“…17,44 A comparison of decellularized organ scaffolds found that fetal and juvenile (3 months old to 1.5 y old) rhesus monkey kidney DECM allowed greater organ repopulation and tubular structure formation than adult (5-13 y old) DECM. 45 Choi and colleagues found that DECM produced by young cells restored a youthful phenotype to senescent human fibroblasts, resulting in an additional 25 population doublings (a 39% increase in cellular lifespan). 46 This finding was applied to female mouse (C57BL/6) BMSCs by Sun and colleagues, who reported that the defective replication of aged (18 months old) BMSCs was reversed by exposure to DECM from young (3 months old) animals.…”

Kidney-Specific Microscaffolds and Kidney-Derived Serum-Free Conditioned Media Support In Vitro Expansion, Differentiation, and Organization of Human Embryonic Stem Cells

“…This interesting article compares the differentiation of HES toward kidney and lung lineages when HES are grown on decellularized kidney and lung slices. The thickness of the slices is not mentioned in this article (or in an earlier article by the same group 35 ), but they appear to be around 2-3 mm based on figure 2 of both articles. Although the matrices are shown to direct correct spatial organization of the cells, overall expression of kidney-and lung-associated markers was not statistically different.…”