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Reconnecting the injured cervical spinal cord by transplanted human iPSC-derived neural progenitors

Award Number: R01NS110707
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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Abstract Axonal degeneration significantly contributes to functional loss after spinal cord injury (SCI). Grafting neural progenitors derived from patients’ own induced pluripotent stem cells (iPSCs) is a promising strategy to establish neuronal relay for reconnecting injured long tracts with their denervated neurons and promoting functional recovery. We hypothesize that co-transplanted human iPSC-derived glial restricted progenitors (GRPs) and neuronal restricted progenitors (NRPs) will work synergistically to form neuronal relays for the injured tracts and that multineurotrophin D15A will direct grafted neurons to form functional synapses with denervated target neurons and promote greater functional recovery in both laceration and contusion cervical SCI animal models. In this proposal, we will test (1) if co-transplanted human iPSC-derived GRPs and NRPs will work synergistically to form neuronal relays for the injured ascending dorsal column tract (DCT) and descending corticospinal tract (CST), and promote functional recovery after C3 dorsal funiculus laceration; (2) if gradient multineurotrophin D15A in dorsal nuclei and caudal ventral horn will direct grafted neurons to extend axons toward and form functional synapses with denervated target neurons of DCT and CST, and promote greater functional recovery; and (3) if grafted NRPs and GRPs will integrate into the spared circuits and promote functional recovery after clinically relevant cervical contusion SCI. Data obtained from the proposed approach will be critical in developing safe and effective patient-specific iPSC-based restorative therapies for SCI in the near future.


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 = $322,656 )
2023	2023	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	4/17/2023	NON-COMPETING CONTINUATION	$322,656
														Subtotal = $322,656

Issue Date FY: 2022 ( Subtotal = $322,656 )
2022	2022	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	4	9/13/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$173,184
2022	2022	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	4/27/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$322,656
2022	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	4/26/2022	NON-COMPETING CONTINUATION	$0
2022	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	9/13/2022	NON-COMPETING CONTINUATION	-$173,184
														Subtotal = $322,656

Issue Date FY: 2021 ( Subtotal = $336,875 )
2021	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	3/18/2021	NON-COMPETING CONTINUATION	$336,875
														Subtotal = $336,875

Issue Date FY: 2020 ( Subtotal = $336,875 )
2020	2020	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	3/23/2020	NON-COMPETING CONTINUATION	$336,875
														Subtotal = $336,875

Issue Date FY: 2019 ( Subtotal = $336,875 )
2019	2019	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/19/2019	NEW	$336,875
														Subtotal = $336,875

Grand Total All Awards = $1,655,937

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Reconnecting the injured cervical spinal cord by transplanted human iPSC-derived neural progenitors

Award Number: R01NS110707

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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