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Near-infrared light controlled transplanted cells to treat spinal cord injury

Award Number: R21NS137121
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: 03/01/2024
PERIOD OF PERFORMANCE END DATE: 09/30/2026

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Near-infrared light controlled transplanted cells to treat spinal cord injury - PROJECT SUMMARY The goal of this project is to develop a prototype transplantation technology based on optogenetically controlled Schwann cells (SCs) and test its efficacy in a rat spinal cord injury (SCI) model. The benefits of using SCs in improving recovery after SCI are well characterized in animal models, yet they have poorly transferred to clinical trials. One major shortcoming of applying SCs in humans involves late injection due to the need for lengthy preparation of autologous SCs. Other major issues concern fast decreases in SC viability and pro-regenerative capacity following transplantation. We intend to address these deficiencies by engineering SCs with higher immune tolerance, and enhanced neuroprotective and neurostimulatory properties. These parameters of the engineered SCs will be controlled with light in the near-infrared window (NIRW) of the spectrum via the recently engineered bacteriophytochrome-based optogenetic system. The NIRW light penetrates deep into mammalian tissues, including the spinal cord. Extracorporeal NIRW light-emitting diodes positioned over the skin will keep engineered SCs in the active state only at the SCI site. Our preliminary results show the feasibility of controlling gene expression in SCs by a bacteriophytochrome-based gene circuit, and the possibility to deliver NIRW light to the spinal cords of rats for extended periods of time. In aim 1, we will engineer optogenetic circuits for NIRW light-inducible expression and secretion of an immunomodulatory cytokine that will dampen the inflammatory and acquired immune responses thus protecting engineered SCs in the irradiated SCI area. This will allow the use of allogeneic SCs thus enabling cell transplantation at acute or sub-acute stages of SCI and avoiding the delay of propagating autologous SCs cells. The engineered SCs will also express, in a light-dependent manner, a neurotrophic factor that promotes neuronal regeneration. Prior to transplantation, the light-inducible immune suppressive and pro-regenerative properties of the engineered SCs will be evaluated in syngeneic and allogeneic co-cultures with immune cells and neurons. In aim 2, we will test performance of the NIRW light- activated allogeneic SCs in a rat model of contusion SCI. We will assess the abundance, activation and localization of the transplanted SCs, the immunological environment at the SCI site, and preliminary assess functional recovery of the animals. This project will be carried out by two research teams with complementary expertise in NIRW optogenetics, neuronal repair and SCI. The high risk associated with engineering and application of optogenetically controlled SCs is mitigated by the potential payoff of developing an allogeneic cell transplantation therapy that can bring the benefits of SCs observed in animal studies to human SCI patients. Further, the proof of concept that transplanted cells can be controlled with NIRW light at the SCI site will broaden application of the NIRW optogenetics to the pro-regenerative cells beyond SCs.


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: 2026 ( Subtotal = $0 )
2026	2025	UNIVERSITY OF WYOMING	1000 E UNIVERSITY AVE	LARAMIE	WY	82071	ALBANY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/27/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $216,750 )
2025	2025	UNIVERSITY OF WYOMING	1000 E UNIVERSITY AVE	LARAMIE	WY	82071	ALBANY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	3/13/2025	NON-COMPETING CONTINUATION	$216,750
														Subtotal = $216,750

Issue Date FY: 2024 ( Subtotal = $180,625 )
2024	2024	UNIVERSITY OF WYOMING	1000 E UNIVERSITY AVE DEPARTMENT 3434	LARAMIE	WY	82071	ALBANY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/21/2024	NEW	$180,625
														Subtotal = $180,625

Grand Total All Awards = $397,375

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Near-infrared light controlled transplanted cells to treat spinal cord injury

Award Number: R21NS137121

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: 03/01/2024

PERIOD OF PERFORMANCE END DATE: 09/30/2026

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