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Ultrasound-assisted extracellular vesicle engineering and induced release: EVEiR

Award Number: R21EB033554
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Ultrasound-assisted extracellular vesicle engineering and induced release: EVEiR - PROJECT SUMMARY While nanoparticle-based platforms have become a leading drug delivery platform for treating various diseases, several challenges remain in current nanomedicine, including toxicity, inefficient endothelial barrier crossing, rapid elimination, and nonspecific accumulation in the body. Extra- cellular vesicles (EVs) provide a natural delivery system that can transfer various cellular cargo to adjacent and distant cells. EVs offer unique advantages for engineering while possessing in- herent immune evasion capability and tissue penetrating characteristics. However, inefficient therapeutic cargo packaging and insufficient EV production from cells limit the current EV-based drug delivery approach. Chronic inflammatory disease (CID) imposes health and economic burdens on communi- ties worldwide. Current therapy of CID is neither sufficient nor disease-modifying. Our ultimate goal is to develop a safe and effective EV-based therapy for CID patients. The overall objectives in this application are to (i) develop an ultrasound (US)-based platform termed EVEiR (Extracel- lular Vesicle Engineering and induced Release) for delivering anti-inflammatory cytokine IL10, and (ii) determine their therapeutic efficacy using an in vitro intestinal model. The central hypoth- esis is that externally applied mechanical cues using US stimulation and the mechanical proper- ties of the cell microenvironment may increase the production and function of engineered EVs (eEVs) derived from mesenchymal stem cells (MSCs) in 3D cultures. We will test the central hypothesis by pursuing two Specific Aims: 1) Develop US-assisted EVEiR for efficient production of anti-inflammatory IL10-carrying eEVs (IL10+ eEVs); and 2) Demonstrate the feasibility of IL10+ eEVs derived from MSCs in 3D cultures for targeted delivery of therapeutics. Aim 1 will determine the efficiency of IL10+ eEV production using the novel US-based techniques. Aim 2 will charac- terize the properties of IL10+ eEVs and their anti-inflammatory effect using an in vitro intestinal model. The innovation of this proposal is to utilize the synergy with the impact of non-viral intra- cellular IL10 packaging in EVs, the unique concept of pulsed US stimulation of MSCs in 3D hy- drogel constructs for efficient eEV production. In addition, an in vitro intestinal model allows for efficient characterization of anti-inflammatory IL10+ eEVs in a physiologically relevant environ- ment. The proposed research is significant because the successful completion of this project will develop a rapid, cost-effective, and scalable platform to generate MSC-derived therapeutic EVs for treating CID and facilitate the translation of MSC-derived EVs to the clinic.


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	2024	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 360	EAST LANSING	MI	48824	INGHAM	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	12/15/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $190,239 )
2024	2024	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	6/21/2024	NON-COMPETING CONTINUATION	$190,239
														Subtotal = $190,239

Issue Date FY: 2023 ( Subtotal = $190,439 )
2023	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	6/26/2023	NON-COMPETING CONTINUATION	$190,439
														Subtotal = $190,439

Issue Date FY: 2022 ( Subtotal = $243,883 )
2022	2022	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	9/1/2022	NEW	$243,883
														Subtotal = $243,883

Grand Total All Awards = $624,561

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Ultrasound-assisted extracellular vesicle engineering and induced release: EVEiR

Award Number: R21EB033554

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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