A printable model for liver disease

Organovo designs and creates functional, 3D human tissues for medical research and therapeutic applications

Lloyd Dunlap
SAN DIEGO—Organovo is collaborating with pharmaceutical and academic partners to develop human biological disease models in three dimensions. These 3D human tissues have the potential to accelerate the drug discovery process, enabling treatments to be developed faster and at lower cost. The company plans to market the first product of a planned portfolio offering 3D Human Liver Tissue for use in toxicology and other preclinical drug testing prior to the end of 2014.
 
Already, an unnamed “opinion leader” has reported that the company’s liver tissue has been used to establish the toxicity of a drug known to induce liver injury in humans that did not display such toxicity in animals or other liver cell-model systems.
 
Organovo’s bioprinting process, invented at the University of Missouri, centers on the identification of key architectural and compositional elements of a target tissue, and the creation of a design that can be utilized by a bioprinter to generate that tissue in the laboratory environment.
 
Once a tissue design is established, the first step is to develop the bioprocess protocols required to generate the multicellular building blocks—also called bio-ink—from the cells that will be used to build the target tissue.
 
The bio-ink building blocks are then dispensed from a bioprinter, using a layer-by-layer approach that is scaled for the target output. Bio-inert hydrogel components may be utilized as supports, as tissues are built up vertically to achieve three-dimensionality, or as fillers to create channels or void spaces within tissues to mimic features of native tissue.
 
The bioprinting process can be tailored to produce tissues in a variety of formats, from microscale tissues contained in standard multiwell tissue culture plates to larger structures suitable for placement onto bioreactors for biomechanical conditioning prior to use.
 
“Currently, pharma doesn’t have good preclinical models,” says Dr. Eric David, chief strategy officer at Organovo. “We’re confident we can provide preclinical models that are better than animal models of cells in a petrie dish. ‘Tissue on demand’ is our long-term vision. At Organovo, we believe that engineered tissues will someday be a routine source of therapy for patients with damaged or diseased tissue.”
 
Today, the company is working, both internally and with select partners, to fulfill its vision of building human tissues for surgical therapy and transplantation. The flexibility of its tissue engineering technology, and its proven application across a wide variety of cells, allows the targeting of many different tissues. The cell source can be either allogenic or autologous (using the patient’s own cells), which could allow Organovo-generated tissue to avoid transplant rejection and the need for lifelong immunosuppressant drugs.
 
Significant science and discovery is required to develop a tissue therapy and ensure safety and efficacy through controlled clinical trials, as well as gain regulatory clearance as a medical device, the company spells out on its website. Supplemental tissue therapies that could come in forms of tubes, patches or organoids are a developmental possibility today. Larger replacement tissues remain a future goal, and the insight gained through the development of supplemental tissue therapies can serve as key guideposts for the ultimate development of functional organ replacements.
 
“The promise for tissue therapies that cure disease with reduced risk of immune rejection, made on demand from cellular building blocks rather than waiting for a limited supply of donor tissues, is a vision we are passionate in pursuing,” Organovo states.
 
Organovo remains on track with its plans to launch a preclinical testing business for experimental drug compounds before the end of this year, company CEO Keith Murphy stated. He says the company plans to offer contract research services based on its 3D human liver tissue technology to drug discovery companies.
 
Earlier this year, the company announced results of its initial study of 3D breast tissues generated with its NovoGen MMX Bioprinter in breast cancer models, which demonstrated that utilizing 3D tissues may enable researchers to make compartment-specific assessments (i.e., epithelium, stroma and vasculature) of drug response—something that is not currently possible outside of in-vivo models. The results were presented at the annual meeting of the American Association for Cancer Research held on April 5-9, 2014, in San Diego.

Lloyd Dunlap

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