# Extracellular vesicles as nanotheranostic platform in neuroinflammation

> **NIH NIH P41** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $265,776

## Abstract

Mesenchymal stem cells (MSCs) are the most widely used type of cells in stem cell therapy, with over 1,000
registered clinical trials primarily focused on immunosuppression of inflammatory disease. “MSCs” are often
termed “medicinal stem cells”, as they secrete multiple beneficial factors in the form of extracellular vesicles
(EVs) that have trophic homing properties for sites of inflammation. However, the use of MSCs is limited by
complex regulatory issues and logistics, low cell viability, and high costs. The field of cell therapy has now
been shifting to the production of EVs as a “cell-free” alternative. Similar to tracking whole cells, it will be
imperative to be able to track the biodistribution of these therapeutic EVs in vivo in order to interpret and
improve therapeutic outcome. We propose to develop two types of labeled MSC-derived EV formulations and
will compare their in vivo imaging (MRI and MPI) and therapeutic properties to unmodified, naïve EVs, that we
hypothesize may still be trackable with CEST MRI by virtue of their mannose-rich membrane composition.
Based upon the existing clinical trials using MSCs in patients with multiple sclerosis (MS) and amyotrophic
lateral sclerosis (ALS), we will evaluate our MSC-EV formulations in vivo using an experimental autoimmune
encephalomyelitis (EAE) MS mouse model and a superoxide dismutase-decificient transgenic ALS mouse
model. To this end, we propose the following specific aims: AIM 1: To develop magnetically labeled MSC-EVs
as a bimodal negative MRI contrast agent and magnetic particle imaging (MPI) tracer. We will use
electroporation to load EVs with superparamagnetic iron oxides (SPIOs). Unlike with MRI, the number of MSC-
SPIO-EVs can be quantified with MPI. AIM 2: To develop gadolinium-labeled MSC-EVs as positive MRI
contrast agent. We will use lipophilic gadolinium chelates and lipid insertion techniques to render EVs with
paramagnetic membranes. AIM 3: To develop unlabeled MSC-EVs as diaCEST MRI contrast agent. We will
take advantage of the natural expression of high-mannose type N glycans on EV membranes which provide
contrast on mannose-weighted CEST MRI, without the need of further vesicle manipulation. AIM 4: To track
the in vivo distribution and therapeutic outcome of labeled and unlabeled EVs in a mouse models of EAE and
ALS. This will serve as an internal JHU validation study. We will investigate various administration routes and
use standard behavioral scoring tests to correlate the diagnostic and therapeutic outcome measures of our
nanotheranostic approach. We will compare and validate all three MSC-EV imaging strategies in terms of
sensitivity, specificity, and EV functionality. Upon proper synthesis, characterization, and in vivo validation, we
will disseminate our SPIO-MSC-EVs, Gd-MSC-EVs, and unlabeled EVs to the CPS, SPs, and beyond.

## Key facts

- **NIH application ID:** 10848986
- **Project number:** 2P41EB024495-06A1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Jeff W. Bulte
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $265,776
- **Award type:** 2
- **Project period:** 2017-09-15 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10848986

## Citation

> US National Institutes of Health, RePORTER application 10848986, Extracellular vesicles as nanotheranostic platform in neuroinflammation (2P41EB024495-06A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10848986. Licensed CC0.

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