Journal
JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
Volume 6, Issue 8, Pages 589-597Publisher
WILEY
DOI: 10.1002/term.471
Keywords
kidney; adult stem cells; tissue expansion; tissue engineering; renal insufficiency
Categories
Funding
- NIH-NIDDK SBIR [1R43DK082050-01, 1R43DK074289-01, 1R43DK074289-02, 1R43DK080529-03, 1R43DK080529-04]
- NIH [5 U42 RR006042-20]
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Renal cell therapy employing cells derived from adult renal epithelial cell (REC) progenitors promises to reduce the morbidity of patients with renal insufficiency due to acute renal failure and end stage renal disease. To this end, tissue engineered devices addressing the neglected biologic component of renal replacement therapy are being developed. Because human donor tissue is limited, novel enhanced progenitor cell propagation (EP) techniques have been developed and applied to adult human kidney transplant discards from six donors. Changes include more efficient digestion and the amplification of progenitors prior to terminal epithelial differentiation promoted by contact inhibition and the addition of retinoic acid. Differentiated morphology in EP populations was demonstrated by the ability to form polarized epithelium with tight junctions, apical central cilia and expression of brush border membrane enzymes. Evaluation of lipopolysaccharide stimulated interleukin-8 secretion and ?glutamyl transpeptisade activity in EP derived cells was used to confirm therapeutic equivalence to REC obtained using published techniques, which have previously shown efficacy in large animal models and clinical trials. Yield exceeded 1016 cells/gram cortex from the only kidney obtained due to an anatomical defect, while the average yield from diseased kidneys ranged from 1.1x109 to 8.8x1011 cells/gram cortex, representing an increase of more than 10 doublings over standard methods. Application of the EP protocol to REC expansion has solved the problem of cell sourcing as the limiting factor to the manufacture of cell based therapies targeting renal diseases and may provide a method for autologous device fabrication from core kidney biopsies. Copyright (c) 2012 John Wiley & Sons, Ltd.
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