Anamik Jhunjhunwala

BME PhD Proposal Presentation

Date: 2023-04-27
Time: 4:00 - 6:00 pm
Location / Meeting Link: IBB Suddath Seminar room (#1128) | https://gatech.zoom.us/j/96427008707

Committee Members:
Andrés García ; Costas Arvanitis ; Leslie Chan ; Jinhwan Kim ; Stanislav Emelianov (Advisor) ; Younan Xia ;


Title: Multifunctional US/PA Nanosensors for Engineering Next-generation Stem Cells

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 assess therapeutic outcomes or even 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 expedite clinical studies, accelerate translation, and achieve maximum efficacy, there is a dire need for the spatial and functional monitoring of grafted SC status in vivo. To address this need, I propose 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. Imaging is a potent tool which can provide critical feedback towards multiple stages of SCT from harvesting, purification, grafting, and therapeutic evaluation. Ideal imaging methods should be non-invasive, have high resolution, possess real-time monitoring capabilities, and allow for monitoring of biological events. 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. This proposal will detail the development of a stimuli-responsive photoacoustic nanosensor model which can be modulated to observe a variety of transplanted SC fates and additionally allow for image-guided therapeutic interventions. Combined with US/PA imaging and stem cell engineering, I hope to achieve (i) real-time, longitudinal tracking of transplanted SC location and apoptotic status using a capsase3-responsive nanosensor, (ii) trimodal US/PA/MR monitoring of stem cell location and apoptosis along with magnetic guidance to target regions and retention, and (iii) US/PA guided tracking of nanosensor augmented SCs and their differentiation coupled with selective photothermal ablation of the adverse phenotypes. Engineering autologous SCs with our nanosensors will impart non-native physicochemical and optical functions, permitting non-invasive spatial and functional cell tracking along with functional control/manipulation. This will enable a new era of SCT with next-generation SCs, with improved therapeutic outcomes and reduced limitations.