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iPS-Glial Restricted Progenitors in White Matter Repair for Stroke

Award Number: R01NS103788
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: 05/15/2018
PERIOD OF PERFORMANCE END DATE: 02/29/2024

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iPS-Glial Restricted Progenitors in White Matter Repair for Stroke - Program Summary Stroke is the leading cause of adult disability. As the population ages, the incidence of stroke is increasing. Improvements in acute stroke care mean that the death rate from stroke is declining. Stroke has thus changed into a disease of chronically disabled survivors. There is no medical therapy that promotes recovery in stroke. This proposal develops a stem cell therapy for a common subtype of stroke, subcortical or “white matter” stroke. White matter stroke occurs in the regions of the brain that carry connections, is the most age-associated in its incidence, and is the second leading cause of dementia (termed vascular dementia). The proposed studies characterize the molecular and cellular process in tissue integration and wound healing of an hiPSC-derived cell in brain repair after white matter stroke. This cell is differentiated from an induced human pluripotent cell (hiPSC cell) into an immature glial cell, and is termed an hiPSC-glia enriched progenitor (hiPSC-GEP). Preliminary studies indicate that transplantation of hiPSC-GEPs into a mouse model of white matter stroke enhances behavioral recovery compared to other hiPSC types, and that this behavioral recovery effect is associated with improvement in the MRI appearance of white matter stroke. The studies in this grant will fully determine the phenotype and tissue integration of hiPS-GEPs, the transcriptional profile of hiPSC-GEPs and the cells of the surrounding stroke environment as these two populations re-organize and inter-relate over time after stroke, the effect of hiPSC-GEPs on stroke using in vivo MRI to track tissue repair, and the efficacy of hiPSC-GEPs in translationally relevant stroke conditions, such as in the aging brain. These studies use an innovative platform that includes a new mouse model, in vivo MRI, Drop-seq single cell transcriptional profiling, and viral reporter and gain and loss of function approaches. The proposed studies bring together a neuroscientist/neurologist and stem cell biologist to develop a novel therapy in a disease with increasing prevalence and no current therapy.


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: 2025 ( Subtotal = -$27,291 )
2025	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	5/13/2025	NON-COMPETING CONTINUATION	$0
2025	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	5/15/2025	NON-COMPETING CONTINUATION	-$27,291
														Subtotal = -$27,291

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	7/11/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $341,250 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	2/2/2022	NON-COMPETING CONTINUATION	$307,125
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	3/28/2022	NON-COMPETING CONTINUATION	$34,125
														Subtotal = $341,250

Issue Date FY: 2021 ( Subtotal = $341,250 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	2/10/2021	NON-COMPETING CONTINUATION	$341,250
														Subtotal = $341,250

Issue Date FY: 2020 ( Subtotal = $341,250 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	6/25/2020	NON-COMPETING CONTINUATION	$341,250
														Subtotal = $341,250

Issue Date FY: 2019 ( Subtotal = $341,250 )
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	2/6/2019	NON-COMPETING CONTINUATION	$341,250
														Subtotal = $341,250

Issue Date FY: 2018 ( Subtotal = $234,000 )
2018	2018	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/4/2018	NEW	$234,000
														Subtotal = $234,000

Grand Total All Awards = $1,571,709

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iPS-Glial Restricted Progenitors in White Matter Repair for Stroke

Award Number: R01NS103788

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: 05/15/2018

PERIOD OF PERFORMANCE END DATE: 02/29/2024

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