-
[show abstract]
[hide abstract]
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.
Tissue Engineering Part A 09/2011; 17(23-24):2891-901. · 4.64 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The goal of this study was the production of a decellularized kidney scaffold with structural, mechanical, and physiological properties necessary for engineering basic renal structures in vitro. Fetal, infant, juvenile, and adult rhesus monkey kidney sections were treated with either 1% (v/v) sodium dodecyl sulfate or Triton X-100 followed by quantitative and qualitative analysis. Comparison of decellularization agents and incubation temperatures demonstrated sodium dodecyl sulfate at 4 degrees C to be most effective in preserving the native architecture. Hematoxylin and eosin staining confirmed the removal of cellular material, and immunohistochemistry demonstrated preservation of native expression patterns of extracellular matrix proteins, including heparan sulfate proteoglycan, fibronectin, collagen types I and IV, and laminin. Biomechanical testing revealed a decrease in the compressive modulus of decellularized compared to fresh kidneys. Layering of fetal kidney explants on age-matched decellularized kidney scaffolds demonstrated the capacity of the scaffold to support Pax2+/vimentin+ cell attachment and migration to recellularize the scaffold. These findings demonstrate that decellularized kidney sections retain critical structural and functional properties necessary for use as a three-dimensional scaffold and promote cellular repopulation. Further, this study provides the initial steps in developing new regenerative medicine strategies for renal tissue engineering and repair.
Tissue Engineering Part A 02/2010; 16(7):2207-16. · 4.64 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Heart disease in women is associated with high levels of morbidity and mortality. Although many of the underlying causes are similar for both genders, cardiovascular disease among women has some unique features, including higher coronary heart disease mortality, higher frequency of sudden cardiac death without previous symptoms, and increased mortality among older women compared to men following a myocardial infarction. During recent years, increasing efforts have been placed on identifying preventive measures, but translation of knowledge from epidemiological studies and clinical trials remain incomplete, particularly in women. The recent launch of the National Institutes of Health's Clinical and Translational Science Award program offers opportunities to address these gaps and represent a unique opportunity to foster a new generation of researchers familiar with important issues regarding women's cardiovascular health.
Journal of Cardiovascular Translational Research 10/2009; 2(3):251-5. · 2.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The renal glomerulus is composed of endothelial and mesangial cells with podocytes contributing to glomerular filtration. Podocyte damage is associated with renal disorders, thus there is interest in these cells for regenerative medicine. These studies investigated the use of extracellular matrix (ECM) to grow third trimester fetal monkey renal cortical cells and to assess mature podocytes in culture. Immunohistochemistry provided a profile of podocyte differentiation with metanephric mesenchyme and developing podocytes nestin positive and synaptopodin negative, whereas mature podocytes were positive for both markers. Primary cell cultures devoid of mature podocytes were established on plastic and renal ECM. A cell population (nestin+/synatopodin-) cultured on renal ECM showed greater proliferative potential compared with plastic with limited podocytes developing in culture over time. Further investigation of individual components of ECM (laminin, fibronectin, collagen I, or collagen IV) indicated that collagen I supported the greatest proliferation similar to renal ECM, whereas a greater number of mature podocytes (nestin+/synaptopodin+) were observed on fibronectin. These results suggest that (1) culture of fetal monkey podocytes can be accomplished, (2) renal ECM and collagen I can support renal cortical cells in vitro, which may recapitulate the developing kidney in vivo, and (3) fibronectin can support podocyte differentiation in vitro.
Pediatric Research 08/2009; 66(4):448-54. · 2.70 Impact Factor
-
David Asmuth,
Ted Wun,
Nicole Mullen,
Eric Garcia,
Erica Chedin,
Erica Whitney,
Michael Gillis,
Kent Anderson, Alice Tarantal,
Nicholas Kenyon,
Fitz-Roy Curry,
Lars Berglund
Clinical and Translational Science 04/2009; 2(2):98-101. · 1.13 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The National Institutes of Health's Clinical and Translational Science Award program has had a profound impact upon the way research is conducted at the University of California, Davis. University of California, Davis was among the first cohort of 12 institutions to receive National Institutes of Health funding for this award, and created its Clinical and Translational Science Center (CTSC) in 2006. The presence of a CTSC has led us to develop new ways of bringing together and supporting researchers from diverse fields, and the CTSC has impacted on virtually every area and infrastructure resource involved in supporting clinical and translational research at our institution.
Journal of Investigative Medicine 02/2009; 57(2):474-6. · 1.96 Impact Factor
