Anamik Jhunjhunwala
BME PhD Defense Presentation

Date: 2025-04-24
Time: 3:00 PM – 5:00 PM ET
Location / Meeting Link: EBB Krone - CHOA Seminar Room | https://gatech.zoom.us/j/98258531812

Committee Members:
Stanislav Emelianov, PhD (Advisor); Andres Garcia, PhD; Costas Arvanitis, PhD; Leslie Chan, PhD; Jinhwan Kim, PhD; Younan Xia, PhD;


Title: Multifunctional Ultrasound/Photoacoustic Nanosensors for Next-Generation Cell Therapy

Abstract:
Stem cells (SCs) have significant potential in the treatment of chronic degenerative diseases through remodeling and repair. Although, promising clinical outcomes of stem cell therapy (SCT) have been reported for various pathologies, including musculoskeletal and spinal degeneration, and Parkinson’s disease, many limitations hinder their clinical translation. A major limitation towards clinical SCT is the lack of techniques to monitor the fate of transplanted SCs such as migration, proliferation, viability, and differentiation in vivo. Current assessment is based on invasive end-point analyses such as biopsies and histological assays, which damage regenerating tissues and do not reflect the real-time dynamics of the microenvironment. To overcome these limitations and enable more effective clinical translation, there is a pressing need for tools that allow spatial and functional monitoring of grafted stem cells in vivo. To address this need, this dissertation presents the development of a non-invasive approach to track the location and status of transplanted SCs in vivo, based on a synergistic combination of bioimaging, nanotechnology, and cell engineering. Across many imaging modalities, combined ultrasound and photoacoustic (US/PA) imaging has shown great potential for functional imaging with deep tissue anatomical information and fine spatial resolution. US/PA imaging augmented with stimuli-responsive multifunctional exogenous nanosensors can monitor a highly orchestrated set of biomolecular events both non-invasively and longitudinally. In Aim 1, we designed a modular triblock peptide biosensor template, functionalized it for caspase-3 responsiveness, and used it to develop a photoacoustic nanosensor capable of detecting apoptosis in mesenchymal stromal cells (MSCs). This enabled simultaneous imaging of cell location and apoptotic status via spectral shifts in the photoacoustic signal. In Aim 2, we addressed the challenge of cell delivery and retention by establishing a dual-nanoparticle labeling strategy, combining gold nanorods and iron oxide nanoparticles. This system enabled image-guided magnetic targeting and multimodal tracking. In Aim 3, we examined the long-term fate of nanoparticle-labeled cells by tracking intracellular nanoparticle dilution and asymmetric inheritance across successive cell generations. Together, this work presents a modular platform for molecularly informed, multimodal SC imaging and tracking. These technologies advance our ability to understand and control stem cell therapies, offering tools that will be critical for improving delivery precision, functional readouts, and translational readiness.