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An In Vitro Model of Stem Cell Innervation of Myotubes

Award Number: R01NS050452
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/23/2005
PERIOD OF PERFORMANCE END DATE: 05/31/2022

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An In Vitro Model of Stem Cell Innervation of Myotubes - Project Description: A long-term goal of the research in our laboratory is to re-create the components and compartments of mammalian systems, and in particular human systems, to engineer functional hybrid models. The previous grant period for this Bioengineering Research Grant (BRG) was to investigate the formation of a model system of the reflex arc with rat then human stem cells. During this funding period we have made the following breakthroughs with this model system that move us closer to the goal of creating a functional in vitro model of the complete reflex arc for applications as a phenotypic drug screening system: 1) A functional human to human NMJ system that can be stimulated by both chemical and electrical means that exhibit dose response measurement capabilities to selected compounds that modulate the NMJ. 2) Demonstrated differentiation of Type II, Type Ia and nociceptive sensory neurons from human stem cells and shown functional, mature electrophysiological properties. 3) Derived human intrafusal fibers from stem cells and demonstrated functional human sensory to human intrafusal fiber innervation. 4) Demonstrated sensory neuron to motoneuron innervation with functional synapse formation. 5) Demonstrated human γ-motoneuron innervation of human intrafusal fibers. The previous grant has led to the publication of 26 manuscripts, 3 submitted and another 6 are in preparation, as well as the submission of 12 patents. Six of the articles are in Biomaterials, which has an impact factor of 8.557, and is the leading journal in the field of Biomedical Engineering. This renewal BRG application seeks to complete the development of the complete reflex arc in vitro using cells derived from human stem cells in Aim 1 and then apply aspects of the system to investigation of Amyotrophic Lateral Sclerosis (ALS) in Aims 2 and 3, respectively. The major innovation of this interdisciplinary proposal is the creation of physiologically realistic human in vitro functional units of the CNS and PNS with the proper cell types, cellular interactions and connectivity for application to enable phenotypic screening systems. This technology integration is necessary as we believe these systems are crucial to the creation of the next generation high-content screening platforms. Our idea is that we can create functional in vitro models of the reflex arc or its components, with cells derived from human stem cells, to then recreate phenotypic disease models. The continuation of the grant will enable 1) A functional human cell based reflex arc in a defined, serum-free environment and 2) application of the motoneuron to muscle segment to understand mechanisms in ALS by investigating combinations of WT and mutant cells from patients and 3) to validate the systems. Our expertise in surface chemistry, Micro- ElectroMechanical Systems (MEMS) fabrication and developmental/cellular/molecular biology enables the construction of complex functional neuronal systems in vitro. Our team possesses the necessary expertise in all aspects of this project, as well as the facilities to effectively and successfully perform the research.


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: 2023 ( Subtotal = -$12,682 )
2023	2020	THE UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	9/8/2023	NON-COMPETING CONTINUATION	-$12,682
														Subtotal = -$12,682

Issue Date FY: 2020 ( Subtotal = $481,578 )
2020	2020	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CENTRAL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	7/23/2020	NON-COMPETING CONTINUATION	$481,578
														Subtotal = $481,578

Issue Date FY: 2019 ( Subtotal = $481,578 )
2019	2019	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	6/6/2019	NON-COMPETING CONTINUATION	$481,578
														Subtotal = $481,578

Issue Date FY: 2018 ( Subtotal = $481,578 )
2018	2018	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	5/21/2018	NON-COMPETING CONTINUATION	$481,578
														Subtotal = $481,578

Issue Date FY: 2017 ( Subtotal = $481,577 )
2017	2017	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	12	6/1/2017	NON-COMPETING CONTINUATION	$481,578
2017	2015	UNIVERSITY OF CENTRAL FLORIDA BOARD OF TRUSTEES, THE	4000 CNTRL FLORIDA BLVD	ORLANDO	FL	32816	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	1/30/2017	NON-COMPETING CONTINUATION	-$1
														Subtotal = $481,577

Issue Date FY: 2016 ( Subtotal = $481,578 )
2016	2016	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	11	8/29/2016	COMPETING CONTINUATION	$481,578
2016	2015	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	8/25/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $481,578

Issue Date FY: 2015 ( Subtotal = $403,428 )
2015	2015	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	1/22/2015	NON-COMPETING CONTINUATION	$403,428
														Subtotal = $403,428

Issue Date FY: 2014 ( Subtotal = $398,732 )
2014	2014	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	9	3/5/2014	NON-COMPETING CONTINUATION	$36,248
2014	2014	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	1/22/2014	NON-COMPETING CONTINUATION	$362,484
														Subtotal = $398,732

Issue Date FY: 2013 ( Subtotal = $388,051 )
2013	2013	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	8	5/24/2013	NON-COMPETING CONTINUATION	$26,138
2013	2013	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	1/17/2013	NON-COMPETING CONTINUATION	$361,913
														Subtotal = $388,051

Issue Date FY: 2012 ( Subtotal = $401,518 )
2012	2012	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	2/7/2012	NON-COMPETING CONTINUATION	$401,518
														Subtotal = $401,518

Issue Date FY: 2011 ( Subtotal = $400,932 )
2011	2011	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	1/31/2011	COMPETING CONTINUATION	$400,932
2011	2009	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	1/28/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $400,932

Issue Date FY: 2009 ( Subtotal = $403,008 )
2009	2009	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	6/11/2009	NON-COMPETING CONTINUATION	$403,008
														Subtotal = $403,008

Issue Date FY: 2008 ( Subtotal = $397,945 )
2008	2008	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	5/27/2008	NON-COMPETING CONTINUATION	$397,945
														Subtotal = $397,945

Issue Date FY: 2007 ( Subtotal = $418,401 )
2007	2007	UNIVERSITY OF CENTRAL FLORIDA	12201 RESEARCH PARKWAY	ORLANDO	FL	32826	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	6/25/2007	NON-COMPETING CONTINUATION	$418,401
														Subtotal = $418,401

Issue Date FY: 2006 ( Subtotal = $427,233 )
2006	2006	CLEMSON UNIVERSITY	PO BOX 345355	CLEMSON	SC	29634	PICKENS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	7/3/2006	NON-COMPETING CONTINUATION	$427,233
														Subtotal = $427,233

Issue Date FY: 2005 ( Subtotal = $386,691 )
2005	2005	CLEMSON UNIVERSITY	PO BOX 345355	CLEMSON	SC	29634	PICKENS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/23/2005	NEW	$386,691
														Subtotal = $386,691

Grand Total All Awards = $6,421,146

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An In Vitro Model of Stem Cell Innervation of Myotubes

Award Number: R01NS050452

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/23/2005

PERIOD OF PERFORMANCE END DATE: 05/31/2022

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