Renal tissue engineering with decellularized rhesus monkey kidneys: age-related differences.

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.

[1]  Q. Al-Awqati,et al.  The kidney papilla is a stem cells niche , 2006, Stem Cell Reviews.

[2]  J. Hacia,et al.  Age‐related gene expression profiles of rhesus monkey bone marrow‐derived mesenchymal stem cells , 2008, Journal of cellular biochemistry.

[3]  M. Yoder,et al.  Changes in the frequency and in vivo vessel-forming ability of rhesus monkey circulating endothelial colony–forming cells across the lifespan (birth to aged) , 2012, Pediatric Research.

[4]  Hiroshi Yagi,et al.  Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix , 2010, Nature Medicine.

[5]  Angela Panoskaltsis-Mortari,et al.  Development of a decellularized lung bioreactor system for bioengineering the lung: the matrix reloaded. , 2010, Tissue engineering. Part A.

[6]  A. Tarantal,et al.  Ontogeny of the Kidney and Renal Developmental Markers in the Rhesus Monkey (Macaca Mulatta) , 2010, Anatomical record.

[7]  L. Saxén Organogenesis of the kidney , 1987 .

[8]  J. A. Oliver,et al.  Ureteric bud cells secrete multiple factors , including bFGF , which rescue renal progenitors from apoptosis , 1997 .

[9]  J. Bertram,et al.  Is there such a thing as a renal stem cell? , 2009, Journal of the American Society of Nephrology : JASN.

[10]  Li Zhang,et al.  The effect of source animal age upon extracellular matrix scaffold properties. , 2011, Biomaterials.

[11]  A. Woolf,et al.  Creation of a functioning chimeric mammalian kidney. , 1990, Kidney international.

[12]  M. Conconi,et al.  Tracheal matrices, obtained by a detergent‐enzymatic method, support in vitro the adhesion of chondrocytes and tracheal epithelial cells , 2005, Transplant international : official journal of the European Society for Organ Transplantation.

[13]  J. Kreisberg,et al.  Glomerular cells in culture. , 1983, Kidney international.

[14]  Anthony Atala,et al.  Tissue-specific extracellular matrix coatings for the promotion of cell proliferation and maintenance of cell phenotype. , 2009, Biomaterials.

[15]  A. Atala,et al.  Randomized comparative study between buccal mucosal and acellular bladder matrix grafts in complex anterior urethral strictures. , 2008, The Journal of urology.

[16]  F. Rae,et al.  Stem cell options for kidney disease , 2009, The Journal of pathology.

[17]  Qiwei Yang,et al.  Update of extracellular matrix, its receptors, and cell adhesion molecules in mammalian nephrogenesis. , 1998, American journal of physiology. Renal physiology.

[18]  M. Yoder,et al.  Ontogeny of CD24 in the human kidney. , 2010, Kidney international.

[19]  M. Yoder,et al.  Characterization and Culture of Fetal Rhesus Monkey Renal Cortical Cells , 2009, Pediatric Research.

[20]  Doris A Taylor,et al.  Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart , 2008, Nature Medicine.

[21]  James J. Yoo,et al.  In vitro generation of three-dimensional renal structures. , 2009, Methods.

[22]  J. Chen,et al.  Differential expression of the intermediate filament protein nestin during renal development and its localization in adult podocytes. , 2006, Journal of the American Society of Nephrology : JASN.

[23]  Naohiro Terada,et al.  Embryonic stem cells proliferate and differentiate when seeded into kidney scaffolds. , 2009, Journal of the American Society of Nephrology : JASN.

[24]  A. McMahon,et al.  Intrinsic epithelial cells repair the kidney after injury. , 2008, Cell stem cell.

[25]  A. Tarantal,et al.  Comparison of growth and differentiation of fetal and adult rhesus monkey mesenchymal stem cells. , 2006, Stem cells and development.

[26]  N. Friedman,et al.  Human and porcine early kidney precursors as a new source for transplantation , 2003, Nature Medicine.

[27]  D. Kohn,et al.  HIV-1-derived lentiviral vectors and fetal route of administration on transgene biodistribution and expression in rhesus monkeys , 2005, Gene Therapy.

[28]  J. Bonventre,et al.  Repair of injured proximal tubule does not involve specialized progenitors , 2011, Proceedings of the National Academy of Sciences.

[29]  Christian Schuetz,et al.  Regeneration and orthotopic transplantation of a bioartificial lung , 2010, Nature Medicine.

[30]  Penny Ackland,et al.  Kidney disease , 2019, Analgesia, Anaesthesia and Pregnancy.

[31]  E. Robertson,et al.  Interaction between FGF and BMP signaling pathways regulates development of metanephric mesenchyme. , 1999, Genes & development.

[32]  Zhen W. Zhuang,et al.  Tissue-Engineered Lungs for in Vivo Implantation , 2010, Science.

[33]  Karina H Nakayama,et al.  Decellularized rhesus monkey kidney as a three-dimensional scaffold for renal tissue engineering. , 2010, Tissue engineering. Part A.

[34]  Joungho Han,et al.  Kidney Tissue Reconstruction by Fetal Kidney Cell Transplantation: Effect of Gestation Stage of Fetal Kidney Cells , 2007, Stem cells.

[35]  M. Yoder,et al.  Renal ontogeny in the rhesus monkey (Macaca mulatta) and directed differentiation of human embryonic stem cells towards kidney precursors. , 2009, Differentiation; research in biological diversity.

[36]  Yimin Zhao,et al.  Clinical transplantation of a tissue-engineered airway , 2009, The Lancet.

[37]  M. Carini,et al.  Regeneration of glomerular podocytes by human renal progenitors. , 2009, Journal of the American Society of Nephrology : JASN.

[38]  A. Tarantal,et al.  Effect of Age on the Frequency, Cell Cycle, and Lineage Maturation of Rhesus Monkey (Macaca mulatta) CD34+ and Hematopoietic Progenitor Cells , 2005, Pediatric Research.