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hiPSC-based DRG Tissue Mimics on Multi-well Microelectrode Arrays as a Tissue Chip Model of Acute and Chronic Nociception

Award Number: UG3TR003149
ORGANIZATION: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project summary/abstract: Chronic pain afflicts up to one in five adults and is the most common cause of long-term disability in the world. Opioids, which are commonly prescribed for non-cancer pain, are associated with a high incidence of serious effects and abuse. Moreover, current in vivo and in vitro models used to study nociception and test potential treatments are inadequate. Human-based, pathology-relevant models of nociception are urgently needed to facilitate preclinical development of new non-opioid pain therapeutics. Therefore, we propose to develop an innovative 3D model of acute and chronic nociception using hiPSC sensory neurons and satellite glial cell surrogates (an hiPSC-based DRG tissue mimic) on multi-well MEAs. In the UG3 phase, we will develop a tissue chip for modeling acute and chronic nociception based on 3D hiPSC-based dorsal root ganglion (DRG) tissue mimics and a high-content, moderate-throughput microelectrode array (MEA) platform. DRG tissue mimics will be comprised of hiPSC counterparts to constituent intraganglionic DRG cell types embedded in a collagen matrix. We will then demonstrate stable spontaneous and noxious stimulus-evoked behavior in response to thermal, chemical, and electrical stimulation challenges. Furthermore, we aim to demonstrate the clear functional and phenotypic advantages of utilizing a 3D mixed-cell DRG tissue mimic versus purely neuronal 2D or 3D models. More specifically, we aim to demonstrate sensitivity to translational control via ligand receptor interactions between neuronal and non-neuronal cell types, thereby demonstrating pathological relevance to a the ‘holy trinity’ of pain (nociceptive, inflammatory and neuropathic) and our model’s capacity for testing fundamental hypotheses related to contributions of non-neuronal support cells in chronic pain development and maintenance. In the UH3 phase, we will demonstrate the powerful quantitative efficiency and preclinical efficacy of our microphysiological system by detecting known ligand-based modulators of translational control and voltage- gated ion channel antagonists in a sensitized model of chronic nociception. These two classes of drugs are widely recognized as candidate compounds for reversing nociceptive plasticity and/or serving as peripheral analgesics. Moreover, we will quantitatively define pharmacological hits based on widely accepted assay scoring methodologies. Lastly, we will leverage the high-throughput nature or our tissue chip model to screen FDA- approved, bioactive compounds, demonstrating the sensitivity and throughput of our high content assay, and potentially identifying efficacy of candidate therapeutics obscured by less sophisticated methods of phenotypic screening.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2022 ( Subtotal = -$256,458 )
2022	2020	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	National Center for Advancing Translational Sciences	001	2	3/29/2022	SUPPLEMENT FOR EXPANSION	-$132,280
2022	2019	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	National Center for Advancing Translational Sciences	000	2	3/29/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$124,178
														Subtotal = -$256,458

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	National Center for Advancing Translational Sciences	006	2	6/7/2021	SUPPLEMENT FOR EXPANSION	-$132,280
2021	2020	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	National Center for Advancing Translational Sciences	007	2	6/8/2021	SUPPLEMENT FOR EXPANSION	$132,280
2021	2020	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	National Center for Advancing Translational Sciences	003	2	3/5/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2019	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	National Center for Advancing Translational Sciences	009	2	8/10/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2021	2019	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	National Center for Advancing Translational Sciences	005	2	4/22/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$601,203
2021	2019	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	National Center for Advancing Translational Sciences	004	2	4/16/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$601,203
2021	2019	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	National Center for Advancing Translational Sciences	008	2	6/10/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2021	2019	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	National Center for Advancing Translational Sciences	002	2	3/5/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2021	2019	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	National Center for Advancing Translational Sciences	000	1	2/21/2021	NEW	-$5,529
2021	2019	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	National Center for Advancing Translational Sciences	010	2	9/13/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2021	2019	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	National Center for Advancing Translational Sciences	001	2	2/21/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$5,529
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $132,280 )
2020	2020	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	National Center for Advancing Translational Sciences	004	2	9/18/2020	SUPPLEMENT FOR EXPANSION	$132,280
2020	2019	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	National Center for Advancing Translational Sciences	000	1	12/13/2019	NEW	$0
2020	2019	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	National Center for Advancing Translational Sciences	001	1	3/26/2020	NEW	$0
2020	2019	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 415	LOWELL	MA	01854	MIDDLESEX	USA	National Center for Advancing Translational Sciences	003	2	9/13/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$601,203
2020	2019	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	National Center for Advancing Translational Sciences	002	1	9/12/2020	NEW	-$601,203
														Subtotal = $132,280

Issue Date FY: 2019 ( Subtotal = $849,217 )
2019	2019	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	National Center for Advancing Translational Sciences	000	1	9/25/2019	NEW	$849,217
														Subtotal = $849,217

Grand Total All Awards = $725,039

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hiPSC-based DRG Tissue Mimics on Multi-well Microelectrode Arrays as a Tissue Chip Model of Acute and Chronic Nociception

Award Number: UG3TR003149

ORGANIZATION: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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