Alpha Omega Alpha Honor Medical Society

2012 Research Abstract

Regeneration and experimental orthotopic transplantation of a bioengineered kidney

Abstract of published paper in Nature Medicine
Article about the study on the Nature web site

Investigator: Jeremy Song, University of California, Irvine, School of Medicine

Mentor: Harald C. Ott, MD, Center for Regenerative Medicine, Massachusetts General Hospital & Harvard Medical School

End-stage renal disease affects nearly 1 million Americans with over 100,000 new diagnoses each year (1). Kidney failure is definitively treated with transplantation; however, donor organ shortage, need for immunosuppression, and chronic rejection limit transplantation’s clinical impact. This study describes a novel process for regenerating functional whole kidneys based upon perfusion-decellularized extracellular matrices (ECM) and biomimetic whole-organ culture. To obtain a 3-dimensional scaffold conducive for regeneration, whole kidneys from human, pig, and rats underwent perfusion decellularization. Analysis of subsequent perfusion decellularized kidney ECMs revealed preserved 3-dimensional ECM protein structure and composition, as well as histologic morphometry when compared to cadaveric kidneys, suggesting an intact 3-dimensional whole organ scaffold capable of supporting functional renal tissue. Next, we hypothesized that this perfusion decellularized kidney ECM was biocompatible, and thus could support the regeneration of functional renal tissue. After seeding human endothelial cells and primitive kidney progenitor cells onto a decellularized kidney ECM followed by biomimetic culture designed to mimic organ developmental conditions, tubular epithelium, renal endothelium, and glomeruli epithelium were repopulated in a site specific manner. We then hypothesized that this regenerated kidney could carry out functions of cadaveric kidneys including filtration, secretion, and reabsorption. To test this hypothesis, we performed bench-top testing of the kidney, and showed rudimentary urine production with clearance of waste metabolites. Furthermore, to test the regenerated kidney’s ability to incorporate into a living body and thus become viable tissue post-operatively, we transplanted the bioengineered kidney into a rat, and demonstrated urine production and clearance of metabolites, in vivo.

The AΩA Carolyn L. Kuckein Student Research Fellowship provided instrumental funding to undertake the above study. Thus, the 2013 AΩA Research Fellowship aided in the first step towards developing, on demand, a bioartificial kidney as a fully implantable treatment option for kidney failure.

1. Centers for Disease Control and Prevention. National chronic kidney disease fact sheet: general information and national estimates on chronic kidney disease in the United States, 2010. 〈http://www.cdc.gov/DIABETES//pubs/factsheets/kidney.htm〉 (2010).

Updated on April 22, 2013.


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