김진환 (Georgia Institute of Technology, 현 University of California, Davis) | 한빛사논문 > 한빛사

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Georgia Institute of Technology, 현 University of California, Davis

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ACS Nano, Sep 13 2023 | https://doi.org/10.1021/acsnano.3c04161 In Vivo Photoacoustic Monitoring of Stem Cell Location and Apoptosis with Caspase-3-Responsive Nanosensors.

Anamik Jhunjhunwala ¹, Jinhwan Kim ^1,2, Kelsey P Kubelick ^1,2, C Ross Ethier ¹, Stanislav Y Emelianov^1,2

¹Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, Georgia 30332, United States.

²School of Electrical & Computer Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.

A.J. and J.K. contributed equally to this work.

Corresponding Authors : C. Ross Ethier, Stanislav Y. Emelianov

Abstract

Stem cell therapy has immense potential in a variety of regenerative medicine applications. However, clinical stem cell therapy is severely limited by challenges in assessing the location and functional status of implanted cells in vivo. Thus, there is a great need for longitudinal, noninvasive stem cell monitoring. Here we introduce a multidisciplinary approach combining nanosensor-augmented stem cell labeling with ultrasound guided photoacoustic (US/PA) imaging for the spatial tracking and functional assessment of transplanted stem cell fate. Specifically, our nanosensor incorporates a peptide sequence that is selectively cleaved by caspase-3, the primary effector enzyme in mammalian cell apoptosis; this cleavage event causes labeled cells to show enhanced optical absorption in the first near-infrared (NIR) window. Optimization of labeling protocols and spectral characterization of the nanosensor in vitro showed a 2.4-fold increase in PA signal from labeled cells during apoptosis while simultaneously permitting cell localization. We then successfully tracked the location and apoptotic status of mesenchymal stem cells in a mouse hindlimb ischemia model for 2 weeks in vivo, demonstrating a 4.8-fold increase in PA signal and spectral slope changes in the first NIR window under proapoptotic (ischemic) conditions. We conclude that our nanosensor allows longitudinal, noninvasive, and nonionizing monitoring of stem cell location and apoptosis, which is a significant improvement over current end-point monitoring methods such as biopsies and histological staining of excised tissue.

논문정보

형식Research article
게재일2023년 09월 (BRIC 등록일 2023-09-27)
연구진국외 연구진
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