Organovo Holdings, a pioneer in the commercial use of 3D bioprinting technology, published data in the Frontiers of Physiology journal showing the company’s 3D bioprinted proximal tubule tissue model exhibits key characteristics of renal physiology that allow for in vitro kidney toxicity testing.
“Traditional preclinical models often fall short in their ability to inform clinical outcomes accurately, largely due to the limited functionality of simple in vitro models and species differences,” said Dr. Sharon Presnell, chief scientific officer, Organovo. “Our newly published data demonstrate that Organovo’s 3D bioprinted human kidney tissue has great potential to assess the toxic effects of compounds and the development and progression of complex, multicellular processes such as fibrosis.”
Key findings and attributes described in the publication include the following:
Immunohistochemical characterization showing tight junction formation between epithelial cells, polarized expression of transporters that regulate excretion and reabsorption of compounds, an extensive microvascular network, and deposition of endogenous extracellular matrix in the interstitium;
Proof-of-concept study for demonstrating induction of toxicity following treatment with a nephrotoxin cisplatin, including a loss of tissue viability and epithelial cell function in a dose-dependent fashion. This effect was blocked by cimetidine, a compound that prevents cisplatin uptake via the transporter OCT2; and Induction of tubulo-interstitial fibrosis in this model via administration of TGF-beta, with tissue response verified via gene expression analysis and histological examination of excess extracellular matrix deposition.
In addition to the kidney publication, the Company noted a recent article published in ILAR Journal. The publication explores new technologies that could reduce both dependency on animal models and occurrence of liver toxicity in clinical trials. The article, written by scientific executives and experts from the Food & Drug Administration (“FDA”), Merck & Co., Inc and LifeNet Health, provides a thorough review of human tissue models and how they can accelerate drug development across all discovery stages, including Organovo’s 3D bioprinted liver model.
The authors reference Organovo’s technology as a “significant innovation in the study of drug-induced liver injury, as it addresses many of the shortcomings associated with traditional in vitro culture models and animal models.” They also state that 3D bioprinted tissues “exhibit a broad range of highly differentiated in vivo like features and functions.”
The authors reference results from Organovo’s drug-induced liver injury studies that have shown “very good reproducibility and concordance with observed outcomes in vivo at the functional and histological levels” and that treatment of the bioprinted human liver model with known fibrotic agents “mimicked closely that of patient liver samples with drug-induced fibrosis.”
“Both liver and kidney drug toxicities are significant challenges for pharmaceutical companies working to advance safe and effective therapeutics,” said Mr. Keith Murphy, CEO, Organovo. “Previous validation data of our 3D bioprinted human liver tissue, combined with the data published in the peer-reviewed journal, Frontiers of Physiology, on our 3D bioprinted kidney proximal tubule tissue, clearly show that Organovo’s technology can address the unmet needs of our pharma customers and partners by providing timely, cost-effective, and more accurate human tissue models for evaluating drug toxicity and drug-induced fibrotic disease.”