Organovo Holdings, Inc., a three-dimensional biology company focused on delivering breakthrough 3D bioprinting technology, presented data on the company's in vitro three-dimensional kidney tissue at the 2015 Experimental Biology conference in Boston, Massachusetts.
"Kidney represents an ideal extension of Organovo's capabilities to 3D bioprint organ tissues that can be tremendously useful in pharmaceutical research," said Keith Murphy, Chairman and Chief Executive Officer at Organovo. "The results released today admirably demonstrate a proof of concept that kidney is on the way to becoming another core commercial tissue for Organovo. The product that we intend to build from these initial results can be an excellent expansion for our core customers in toxicology, who regularly express to us an interest in having better solutions for the assessment of human kidney toxicity."
For the first time, fully human kidney proximal tubular tissues have been generated that are three-dimensional, and consist of multiple tissue-relevant cell types arranged to recapitulate the renal tubular / interstitial interface. The tissues are fabricated using Organovo's proprietary NovoGenTM bioprinting platform, and will ultimately join the company's exVive3DTM Liver tissues to expand the repertoire of physiologically-relevant tissue systems available for toxicity and efficacy testing as well as disease modeling. Dr. Sharon Presnell, Chief Technology Officer and Executive Vice President of Research and Development, stated, "Our bioprinted human kidney tissue represents a significant technical advance over the simple monolayer cell line cultures that predominate today. The histologic and functional features of the initial prototypes are compelling, and the in vitro durability of the system will likely enable the assessment of drug effects at chronic, physiologically relevant doses. Furthermore, the cellular complexity of the system will likely support mechanistic investigations into drug responses, including end points that have been difficult or impossible to assess in vitro, including tubular fibrosis and post-injury recovery."
Key findings and attributes from Organovo's research include:
The kidney proximal tubule tissue is multi-cellular and fully human, consisting of polarized renal proximal tubular epithelial cells (RPTEC) and a living interstitial layer comprised of renal fibroblasts (RF), and endothelial cells (EC)
Immunohistochemical analysis shows clear evidence of intercellular junction formation (E-Cadherin+) between the epithelial cells, extensive formation of microvascular structures, and stable maintenance of the layered architecture for at least two weeks in vitro
The epithelial cells within the multi-layered tubular model express CYP450 mRNAs and possess gamma glutamyl transferase (GGT) activity, both of which are indicators of RPTEC function. Importantly, our initial characterization shows that the expression of GGT increases over two weeks post-fabrication, indicating a gain-of-function over time.