The high failure rate of drugs during clinical trials after lab testing highlights the shortcomings of current lab test methods in predicting drug performance in humans. Individual organ cells, cultured in static media and maintained on flat plastic, lack the specific architecture and blood flow perfusion of natural tissues. Animal models used to perform drug absorption, distribution, metabolism and excretion (ADME) studies pose a fundamental species difference with known limitations for predicting drug effects in humans. To better predict drug efficacy and toxicity in humans during lab testing, Draper developed a platform capable of sustaining living human tissue that behaves in key ways like a human: Barrier-Immune-Organ: Microphysiology, Microenvironment Engineered TIssue Construct Systems (BIOMIMETICS). Eventually, BIOMIMETICS should be capable of mimicking ADME processes in humans.
BIOMIMETICS uses sophisticated microfluidics to integrate human cell tissue from multiple organs to recapitulate an organ system, including interactions between organs. Draper demonstrated its BIOMIMETICS platform in several multi-organ model applications. One of these is EVATAR, a BIOMIMETICS configuration Draper engineered to enable better understanding and treatment of female reproductive issues and disease states and better prediction of reproductive toxicity for new treatments in a collaboration with researchers at Northwestern University Medical School.
The EVATAR microfluidic culture model of the human female reproductive system is an example of Draper’s BIOMIMETICS interacting multiple-organ platform that will enable testing drugs’ effects on human physiology with greater predictive power than animal studies.
EVATAR’s BIOMIMETICS captures data on how organs interact with each other and to clinical compounds over a period of a month or more. EVATAR includes ovarian, fallopian, uterine, cervical and liver tissue, cultured in modules programmably controlled by a computer to mimic female endocrine physiology. Microfluidic channels connect the modules, delivering pumped nutrients and cellular signaling molecules to the tissues and carrying away metabolic waste. The channels also support consistent pituitary hormone circulation, and therefore replicate hormonal control of the system’s tissue function.
In testing, the EVATAR system has run more than 100 days through several menstrual cycles, demonstrating reliable performance. The system reproduced the full 28-day menstrual cycle in terms of on-chip ovulation and the concomitant dynamic hormonal profiles (estrogen and progesterone) under our synthetic pituitary control.
In another multi-organ system, a BIOMIMETICS platform recapitulated interactions between liver and airway models over periods of 14 days using cultured human primary cells in a dynamic microfluidic system. Liver and airway models maintained organ-specific tissue morphology and function, including albumin production and oxidative enzyme activity in the liver in circulating common media. The interconnected airway model maintained barrier function and mucus production, as well as lung-specific biomarkers of tissue health.
Toward the ultimate goal of developing a BIOMIMETICS configuration to mimic ADME in humans, Draper has been developing models of individual organs. For the ADME process key organs are gut/intestine (absorption), vascular (distribution), liver (metabolism) and kidney (excretion). Furthest in development is a kidney model that Draper is developing with internal research and development funds. Through projects with Pfizer, Draper is developing models of the human gut, liver and vasculature; Draper expects to qualify these models by the end of 2018. Once the key models have been qualified, integrating them into a BIOMIMETICS ADME configuration becomes possible, paving the way to a more-predictive lab test for assessing the impact of drugs on humans before clinical trials.
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