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Multimodal approach investigating the immunomodulatory effect ofneural stem cells in stroke recovery

Award Number: R01NS058784
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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Human neural stem cell (hNSC) therapy for stroke is showing promise as it moves from the bench into early clinical trials to treat the long term disabilities resulting from stroke. This provides hope for the millions of Americans living with the chronic, debilitating effects of stroke. Major questions remain, however, about how stem cells injected into the brain drive stroke recovery. A clue to stem cell mechanism of action is the recent discovery of the positive correlation between stroke recovery and a brain MRI signal – T2-FLAIR signal– in stroke patients treated with stem cells. We have successfully reproduced this stem cell-induced FLAIR signal in stroke-injured rats, and shown that its associated with inflammation. This led to our central hypothesis: stem cell transplantation drives recovery by inducing a regenerative inflammatory response. The objective of this grant is to use a rat model of subcortical stroke to investigate the immunomodulatory effects of hNSC transplanted at the chronic stage of stroke, at the regional, cellular and molecular levels using a multimodal approach. In Aim1 we use MRI and PET imaging to identify which brain regions show inflammatory changes after hNSC transplantation, and which inflammatory regions best correlate with recovery. This will also test the utility of these clinically relevant imaging modalities as biomarkers for stroke recovery. In Aim 2 we identify the immune changes induced by hNSC treatment using multiple tools to characterize the types and molecular signatures of the immune cells present, and their spatial interactions. In Aim 3 we determine which hNSC-secreted factors modulate the immune response by testing several candidates, in vitro and in vivo, using CRISPR tools to modulate expression of key candidate factors. We will study the impact of manipulating the levels of these proteins on stroke recovery and immunomodulation. Upon conclusion of the study, we will have made significant advancements in understanding how hNSC-induced immunomodulation affects brain repair. This contribution is significant because it will: a) identify potential biomarkers, both pre- and post-treatment, for hNSC-induced recovery; b) begin to delineate the molecular pathways involved in brain repair; and c) ultimately lead to identification of novel therapies for stroke.


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 = $611,978 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	1/30/2023	NON-COMPETING CONTINUATION	$611,978
														Subtotal = $611,978

Issue Date FY: 2022 ( Subtotal = $609,849 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	12	4/15/2022	NON-COMPETING CONTINUATION	$60,986
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	2/1/2022	NON-COMPETING CONTINUATION	$548,863
														Subtotal = $609,849

Issue Date FY: 2021 ( Subtotal = $618,648 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	1/20/2021	NON-COMPETING CONTINUATION	$618,648
														Subtotal = $618,648

Issue Date FY: 2020 ( Subtotal = $629,968 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	2/17/2020	NON-COMPETING CONTINUATION	$629,968
														Subtotal = $629,968

Issue Date FY: 2019 ( Subtotal = $639,541 )
2019	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	9	4/17/2019	COMPETING CONTINUATION	$639,541
2019	2016	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	11/28/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $639,541

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2016	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	8	1/29/2017	EXTENSION WITH OR WITHOUT FUNDS	$87,431
2017	2015	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	1/29/2017	NON-COMPETING CONTINUATION	-$87,431
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $429,536 )
2016	2016	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	8/22/2016	EXTENSION WITH OR WITHOUT FUNDS	$429,536
														Subtotal = $429,536

Issue Date FY: 2015 ( Subtotal = $446,009 )
2015	2015	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	8/20/2015	NON-COMPETING CONTINUATION	$446,009
														Subtotal = $446,009

Issue Date FY: 2014 ( Subtotal = $455,487 )
2014	2014	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	7/8/2014	NON-COMPETING CONTINUATION	$455,487
														Subtotal = $455,487

Issue Date FY: 2013 ( Subtotal = $465,850 )
2013	2013	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	6/28/2013	COMPETING CONTINUATION	$465,850
														Subtotal = $465,850

Issue Date FY: 2011 ( Subtotal = $421,669 )
2011	2011	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	7/11/2011	NON-COMPETING CONTINUATION	$421,669
														Subtotal = $421,669

Issue Date FY: 2010 ( Subtotal = $514,530 )
2010	2010	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	4/27/2010	SUPPLEMENT FOR EXPANSION	$80,173
2010	2010	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	7/14/2010	NON-COMPETING CONTINUATION	$434,357
														Subtotal = $514,530

Issue Date FY: 2009 ( Subtotal = $397,106 )
2009	2009	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	7/17/2009	NON-COMPETING CONTINUATION	$397,106
														Subtotal = $397,106

Issue Date FY: 2008 ( Subtotal = $404,210 )
2008	2008	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	7/25/2008	NEW	$404,210
														Subtotal = $404,210

Grand Total All Awards = $6,644,381

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Multimodal approach investigating the immunomodulatory effect ofneural stem cells in stroke recovery

Award Number: R01NS058784

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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