# In vivo Photoacoustic Monitoring of Stem Cell Differentiation to Cancer Associated Fibroblasts

> **NIH NIH F31** · GEORGIA INSTITUTE OF TECHNOLOGY · 2024 · $48,974

## Abstract

PROJECT SUMMARY
Stem cell therapy (SCT) has displayed immense potential in a variety of regenerative medicine applications
through tissue remodeling and repair. Stem cells (SCs) not only repair injured tissue through direct differentiation
towards mesenchyme lineages, but they also have a multitude of paracrine mechanisms which help in
regeneration. Mesenchymal SCs (MSCs) are the most used SCs due to their easy isolation (from bone marrow
or discarded adipose tissue), no ethical concerns and straightforward maintenance. However, SCT has not
achieved clinical acceptance due to a variety of limiting factors such as injections to incorrect locations, lack of
cell retention, poor viability of transplanted MCSs, and a high risk of protumorigenic activity. Among these a
major roadblock to translation is the ability of transplanted MSCs to differentiate into cancer associated
fibroblasts (CAFs). CAFs contribute to immune escape of tumors via multiple mechanisms, including secretion
of multiple cytokines and chemokines and reciprocal interactions that mediate the recruitment of immune cells.
Moreover, CAFs directly abrogate the function of cytotoxic lymphocytes, thus inhibiting killing of tumor cells.
Clinical stem cell therapy is severely hindered by the lack of spatial and functional information about the fate of
implanted cells in vivo. There is a great need for imaging tools that can provide non-invasive and longitudinal
information about the location of MSCs and the differentiation of MSCs to CAFs. Present methods to determine
therapeutic outcomes are all invasive end-point analyses such as histology and biomarker assays, which cause
damage to regenerating tissue and do not reflect the real-time dynamics of the microenvironment. This project
presents a stimuli-responsive ultrasound guided photoacoustic (US/PA) nanosensor consisting of a gold
nanosphere modified with a LOXL2-responsive triblock peptide. The nanosensor is designed for US/PA
monitoring of MSC location and detection of MSC differentiation to CAFs. The triblock peptide sequence is
selectively cleaved by LOXL2 upon differentiation to CAF phenotypes, which triggers hydrophobic aggregation
of the gold nanospheres leading to enhanced optical absorption in the first near-infrared optical window.
The overall hypotheses of the project are that US/PA imaging of MSCs augmented with LOXL2-responsive
plasmonic nanosensors will enable real-time spatial tracking of transplanted MSCs and allow monitoring of their
differentiation to CAFs in vivo. This approach will facilitate communication between the transplanted SCs and
researchers or clinicians. Successful completion of the aims will (i) showcase and validate a versatile nanosensor
platform for the functional monitoring of transplanted MSCs via integration of non-invasive US/PA imaging with
cell nanoengineering techniques, (ii) perform in vivo real-time US/PA guided tracking of nanosensor augmented
MSCs and their differentiation into CAFs in clinica...

## Key facts

- **NIH application ID:** 10826623
- **Project number:** 1F31AG082500-01A1
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Anamik Jhunjhunwala
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-06-24 → 2027-06-23

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10826623

## Citation

> US National Institutes of Health, RePORTER application 10826623, In vivo Photoacoustic Monitoring of Stem Cell Differentiation to Cancer Associated Fibroblasts (1F31AG082500-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10826623. Licensed CC0.

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