Organ-on-a-chip tools that recapitulate human biology, physiology and pathology are critically needed in basic and applied science research, toxicology, and drug lead development to, ultimately, extend and improve the quality of life by advancing knowledge and expediting discovery while reducing research costs and animal sacrifice. Unfortunately, most products incorporating circulation mimicking perfusion are too complicated for researchers to use, incompatible with many protocols and reads, and low-throughput. Our goal is to change this for ordinary lab personnel and for researchers across disciplines. We will make a researcher-centric product which does not require special skills or training for use, a tool that is flexible enough to serve diverse research objectives, and a tool which for pharmaceutical industry means a simple, low-cost platform for more predictive, multiplexed testing of drugs and drug combination strategies. Lena Biosciences' organs-on-a-chip will comprise artificial vasculature and be in a standard, screening- accessible format known to any user in life sciences, biotechnology and drug discovery for ease of use and user adoption. This platform will support vascularized 3D organ models for physiologically closer drug delivery and distribution by mimicking vasculature-to-tissue resistance and intra-tissue resistance to drug transport. It will be especially well suited for in vitro testing of humanized, high molecular weight therapeutics which are administered to patients intravenously and retained in circulation for the period of weeks. The platform will further provide concentrated cel secretome, proteome, metabolome, degradome, interactome etc. to facilitate detection and identification of biomarkers of therapeutic efficacy, cellular and biochemical changes in response to drugs and other stimuli, and therefore serve as a diagnostic and prognostic research tool in order to, for example, prevent serious reactions in clinical trials. Next, this organ-on-a-chip tool will also lend itself useful for development of de novo drug resistant tissue clones. The acquired-drug-resistance tissue clones will enable testing of new drug combinations that are critically needed for approved frontline therapy drugs on which patients eventually relapse. Lastly, this platform will be in sufficient throughput, compliant with most protocols, assays, reads and imaging setups researchers use routinely, and have zero dead volume to minimize use of expensive developmental drugs. The platform utility will be demonstrated using 3D models of liver, brain and breast cancer, and further validated by demonstrating in vitro testing of drugs and their combinations.
Public Health Relevance Statement: Public Health Relevance: This vascularized organ-on-a-chip research platform will enable tissue fingerprinting and drug testing in vitro, in perfused organ models. It will advance public health by enabling faster, low-cost testing of drug candidates for the ultimate safe and effective treatment of cancer, inflammatory, infectious, autoimmune, neurological and cardiovascular diseases.
NIH Spending Category: Aging; Biotechnology; Breast Cancer; Cancer; Digestive Diseases; Liver Disease; Neurosciences
Project Terms: acquired drug resistance; Adoption; Alzheimer's Disease; Animals; Antibody-drug conjugates; Applied Research; Area; Astrocytes; Autoimmune Diseases; Automation; base; Basic Science; Biochemical; Biological Assay; Biological Models; Biological Sciences; biomarker identification; Biotechnology; Blood; Blood Circulation; Brain; brain cell; Brain Diseases; Breast Cancer Model; Cancer Model; Cancer Patient; cancer therapy; Cardiovascular Diseases; Cell Count; Cell Culture Techniques; Cell Line; Cell surface; cell type; Cells; Clinical; Clinical Trials; Communicable Diseases; Complex; cost; design; Detection; Development; Diagnostic; Discipline; Disease model; Dose; Drops; drug candidate; Drug Combinations; Drug Delivery Systems; drug development; drug discovery; drug distribution; drug efficacy; Drug Exposure; Drug Industry; Drug Kinetics; Drug resistance; Drug Targeting; drug testing; Drug Transport; effective therapy; efficacy testing; ERBB2 gene; Extracellular Matrix; Fingerprint; flexibility; Gel; Goals; hazard; Hepatocyte; HepG2; Hour; Human; Human Biology; Human Resources; humanized monoclonal antibodies; Image; Immune; Immune system; Immune System Diseases; Immunity; improved; In Situ; In Vitro; in vitro testing; in vivo; Infection; Inflammatory; Knowledge; Laboratories; Lead; Letters; Liver; liver injury; macrophage; malignant breast neoplasm; Malignant neoplasm of brain; Malignant neoplasm of liver; Malignant Neoplasms; Mammary Neoplasms; metabolome; Microglia; Modeling; Molecular Weight; Monoclonal Antibodies; Multiple Sclerosis; Nerve Degeneration; nervous system disorder; neuroinflammation; Neurons; novel drug combination; Organ; Organ Model; Parkinson Disease; Pathology; Patients; Perfusion; Pharmaceutical Preparations; Pharmacotherapy; Physiology; prevent; prognostic; Proteome; Protocols documentation; Public Health; public health relevance; Quality of life; Reaction; Reading; Relapse; relapse patients; Research; Research Personnel; Resistance; Resistance development; response; Risk; Role; Safety; safety study; safety testing; scaffold; screening; skills; small molecule; Societies; Stimulus; Stroke; success; sucking; System; Technology; Testing; Therapeutic; three dimensional cell culture; three-dimensional modeling; Time; Tissue Model; Tissues; tool; Toxic effect; Toxicology; Training; Trastuzumab; Trauma; Treatment Efficacy; Tube; tumor; tumor growth; uptake
