Development of a stem cell tracking platform for ophthalmic applications using ultrasound and photoacoustic imaging

• Type of Material: Article
• Authors: Kelsey P. Kubelick, Georgia Institute of Technology; Eric J. Snider, Georgia Institute of Technology; Christopher Ethier, Emory University; Stanislav Emelianov, Emory University
• Language: English
• Date: 2019-01-01
• Publisher: Ivyspring International Publisher
• Publication Version: Final Published Version
• Copyright Statement: © Ivyspring International Publisher. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.7150/thno.32546
• Title of Journal or Parent Work: Theranostics
• ISSN: 1838-7640
• Volume: 9
• Issue: 13
• Start Page: 3812
• End Page: 3824
• Grant/Funding Information: This work was performed in part at Georgia Tech's Institute for Electronics and Nanotechnology, a member of the National Nanotechnology Coordinated Infrastructure, which is supported by the National Science Foundation (grant no. ECCS-1542174).; The authors acknowledge support from the Georgia Research Alliance (GRA), National Institutes of Health (NIH), and the National Science Foundation (NSF).
• Keywords: ultrasound/photoacoustic imaging; TRABECULAR MESHWORK; EYE; Research & Experimental Medicine; glaucoma; GOLD NANORODS; Medicine, Research & Experimental; regenerative medicine; SELECTIVE LASER TRABECULOPLASTY; trabecular meshwork; ANTERIOR SEGMENT; stem cell tracking; Science & Technology; MODEL; IN-VIVO; GLAUCOMA; Life Sciences & Biomedicine; TRANSPLANTATION; OPTICAL COHERENCE TOMOGRAPHY
• Research Categories: Engineering, Biomedical

Abstract

Glaucoma is the second leading cause of blindness in the world. Disease progression is associated with reduced cellularity in the trabecular meshwork (TM), a fluid drainage tissue in the anterior eye. A promising therapy seeks to deliver stem cells to the TM to regenerate the tissue and restore its function. However, like many stem cell-based regenerative therapies, preclinical development relies heavily on histology to evaluate outcomes. To expedite clinical translation, we are developing an ultrasound/photoacoustic (US/PA) imaging platform for longitudinal tracking of stem cells in the anterior eye. Methods: Mesenchymal stem cells (MSCs) were labeled with gold nanospheres in vitro and injected through the cornea into the anterior chamber of ex vivo porcine eyes. Physiological pressure was imposed to mimic in vivo conditions. AuNS-labeled MSCs were injected through the cornea while single-wavelength US/PA images were acquired. At 5 hours post-injection, three-dimensional multi-wavelength US/PA datasets were acquired and spectroscopic analysis was used to detect AuNS-labeled MSCs. US/PA results were compared to fluorescent microscopy. Results: The US/PA imaging platform was able to provide real-time monitoring of the stem cell injection and distinguish AuNS-labeled MSCs from highly absorbing background tissues in the anterior segment. Conclusion: Our US/PA imaging approach can inform preclinical studies of stem cell therapies for glaucoma treatment, motivating further development of this theranostic imaging tool for ophthalmic applications.