Funded Projects

Project # Project Title Sort descending Research Focus Area Research Program Administering IC(s) Institution(s) Investigator(s) Location(s) Year Awarded
1UG3TR003149-01
hiPSC-based DRG Tissue Mimics on Multi-well Microelectrode Arrays as a Tissue Chip Model of Acute and Chronic Nociception Preclinical and Translational Research in Pain Management Development of Novel Drugs and Human Cell-Based Screening Platforms to Treat Pain and Opioid Use Disorder NCATS UNIVERSITY OF TEXAS DALLAS BLACK, BRYAN JAMES Dallas, TX 2019
FOA Title: HEAL Initiative: Tissue Chips to Model Nociception, Addiction, and Overdose (UG3/UH3 Clinical Trial Not Allowed)
FOA Number: RFA-TR-19-003
Summary:

Researchers will develop an innovative three-dimensional (3D) model of acute and chronic nociception using human induced pluripotent stem cell (hiPSC) sensory neurons and satellite glial cell surrogates. They will develop a tissue chip for modeling acute and chronic nociception based on 3D hiPSC-based dorsal root ganglion tissue mimics and a high-content, moderate-throughput microelectrode array. Researchers will demonstrate stable spontaneous and noxious stimulus-evoked behavior in response to thermal, chemical, and electrical stimulation challenges. They aim to demonstrate sensitivity to translational control via ligand receptor interactions between neuronal and non-neuronal cell types. They also will demonstrate the quantitative efficiency and preclinical efficacy of our system by detecting known ligand-based modulators of translational control and voltage-gated ion channel antagonists in a sensitized model of chronic nociception. Researchers will leverage the high-throughput nature of our tissue chip model to screen Food and Drug Administration–approved bioactive compounds.

1UG3TR003150-01
Human Microphysiological Model of Afferent Nociceptive Signaling Preclinical and Translational Research in Pain Management Development of Novel Drugs and Human Cell-Based Screening Platforms to Treat Pain and Opioid Use Disorder NCATS TULANE UNIVERSITY OF LOUISIANA MOORE, MICHAEL J; ASHTON, RANDOLPH S; RAJARAMAN, SWAMINATHAN New Orleans, LA 2019
FOA Title: HEAL Initiative: Tissue Chips to Model Nociception, Addiction, and Overdose (UG3/UH3 Clinical Trial Not Allowed)
FOA Number: RFA-TR-19-003
Summary:

This project will develop a human cell-based model of the afferent pain pathway in the dorsal horn of the spinal cord. The research team’s approach utilizes novel human pluripotent stem cell (hPSC)-derived phenotypes in a model that combines 3D organoid culture with microfabricated systems on an integrated, three-dimensional (3D) microelectrode array. Researchers will establish the feasibility of a physiologically relevant, human 3D model of the afferent pain pathway that will be useful for evaluation of candidate analgesic drugs. They will then improve the physiological relevance of the system by promoting neural network maturation before demonstrating the system’s utility in modeling adverse effects of opioids and screening compounds to validate the model. Completion of the study objective will establish novel protocols for deriving dorsal horn neurons from hPSCs and create the first human microphysiological model of the spinal cord dorsal horn afferent sensory pathway.

1UG3TR003090-01
Joint Pain on a Chip: Mechanistic Analysis, Therapeutic Targets, and an Empirical Strategy for Personalized Pain Management Preclinical and Translational Research in Pain Management Development of Novel Drugs and Human Cell-Based Screening Platforms to Treat Pain and Opioid Use Disorder NCATS UNIVERSITY OF PITTSBURGH AT PITTSBURGH GOLD, MICHAEL S; LIN, HANG Pittsburgh, PA 2019
FOA Title: HEAL Initiative: Tissue Chips to Model Nociception, Addiction, and Overdose (UG3/UH3 Clinical Trial Not Allowed)
FOA Number: RFA-TR-19-003
Summary:

The research team developed an in vitro multi-component joint on a chip (microJoint), in which engineered osteochondral complexes, synovium, and adipose tissues were integrated. This study will introduce sensory innervation into the microJoint and a neuron-containing microfluidic ally will be developed to innervate the microJoint. The osteoarthritis (OA) model will be created in the Neu-microJoint system. The research team will assess activation and/or sensitization of nociceptive afferents with electrophysiology, as well as neurite outgrowth. They will mechanically insult the Neu-microJoint and assess the emergence of “pain” in response to prolonged mechanical stress. Researchers will assess the impact of drugs used clinically for management of OA on OA models and will then use “omic” approaches to identify new biomarkers and therapeutic targets. Researchers will assess the impact of opioids—which they hypothesize will increase the rate of joint degeneration and potentiate the release of pain-producing mediators—on neural activity in the presence and absence of joint injury, as well as the integrity of all joint elements.

1UG3TR003081-01
Multi-organ human-on-a-chip system to address overdose and acute and chronic efficacy and off-target toxicity Preclinical and Translational Research in Pain Management Development of Novel Drugs and Human Cell-Based Screening Platforms to Treat Pain and Opioid Use Disorder NCATS UNIVERSITY OF CENTRAL FLORIDA HICKMAN, JAMES J; SHULER, MICHAEL L Orlando, FL 2019
FOA Title: HEAL Initiative: Tissue Chips to Model Nociception, Addiction, and Overdose (UG3/UH3 Clinical Trial Not Allowed)
FOA Number: RFA-TR-19-003
Summary:

This project will build overdose models for fentanyl, methadone, codeine, and morphine in a multi-organ system and evaluate the acute and repeat dose, or chronic effects, of overdose treatments as well as off-target toxicity. Researchers developed a system using human cells in a pumpless multi-organ platform that allows continuous recirculation of a blood surrogate for up to 28 days. They will develop two overdose models for male and female phenotypes based on pre-Bӧtzinger Complex neurons and will integrate functional immune components that enable organ-specific or systemic monocyte actuation. Models for cardiomyopathy and infection will be utilized. Researchers will establish a pharmacokinetic/pharmacodynamic model of overdose and treatment to enable prediction for a range of variables. We will use a serum-free medium with microelectrode arrays and cantilever systems integrated on chip that allow noninvasive electronic and mechanical readouts of organ function.

1UG3TR003148-01
Multi-organ-on-chip device for modeling opioid reinforcement and withdrawal, and the negative affective component of pain: a therapeutic screening tool. Preclinical and Translational Research in Pain Management Development of Novel Drugs and Human Cell-Based Screening Platforms to Treat Pain and Opioid Use Disorder NCATS UNIVERSITY OF CALIFORNIA LOS ANGELES MAIDMENT, NIGEL T; ASHAMMAKHI, NUREDDIN ; KHADEMHOSSEINI, ALI ; SEIDLITS, STEPHANIE KRISTIN; SVENDSEN, CLIVE NIELS Los Angeles, CA 2019
FOA Title: HEAL Initiative: Tissue Chips to Model Nociception, Addiction, and Overdose (UG3/UH3 Clinical Trial Not Allowed)
FOA Number: RFA-TR-19-003
Summary:

Researchers will develop multi-organ, microphysiological systems (MPSs) based on human induced pluripotent stem cell-derived midbrain-fated dopamine (DA)/gamma-aminobutyric acid neurons on a three-dimensional platform that incorporates microglia, blood–brain barrier (BBB), and liver metabolism. RNA sequencing and metabolomics analyses will complement the primary DA release measure to identify novel mechanisms contributing to chronic opioid-induced plasticity in DA responsiveness. The chronic pain-relevant aspect of the model will be realized by examination of aversive kappa-mediated opioid effects on DA transmission in addition to commonly abused mu opioid receptor agonists, and by incorporation of inflammatory-mediating microglia. Incorporation of BBB and liver metabolism modules into the microphysiologic system platform will permit screening of drugs. Throughput will be increased by integration of online sensors for online detection of DA and other analytes. Researchers will use a curated set of 100 chemical genomics probes.