Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan 48105, United States.
IMRA America Inc., Ann Arbor, Michigan 48105, United States.
ACS Nano. 2024 Jun 11;18(23):14893-14906. doi: 10.1021/acsnano.3c10632. Epub 2024 May 27.
Stem cell therapies are gaining traction as promising treatments for a variety of degenerative conditions. Both clinical and preclinical studies of regenerative medicine are hampered by the lack of technologies that can evaluate the migration and behavior of stem cells post-transplantation. This study proposes an innovative method to longitudinally image human-induced pluripotent stem cells differentiated to retinal pigment epithelium (hiPSC-RPE) cells by multimodal photoacoustic microscopy, optical coherence tomography, and fluorescence imaging powered by ultraminiature chain-like gold nanoparticle cluster (GNC) nanosensors. The GNC exhibits an optical absorption peak in the near-infrared regime, and the 7-8 nm size in diameter after disassembly enables renal excretion and improved safety as well as biocompatibility. In a clinically relevant rabbit model, GNC-labeled hiPSC-RPE cells migrated to RPE degeneration areas and regenerated damaged tissues. The hiPSC-RPE cells' distribution and migration were noninvasively, longitudinally monitored for 6 months with exceptional sensitivity and spatial resolution. This advanced platform for cellular imaging has the potential to enhance regenerative cell-based therapies.
干细胞疗法作为多种退行性疾病有希望的治疗方法正在受到关注。再生医学的临床前和临床研究都受到缺乏能够评估移植后干细胞迁移和行为的技术的阻碍。本研究提出了一种创新的方法，通过多模态光声显微镜、光学相干断层扫描和荧光成像，对人诱导多能干细胞分化为视网膜色素上皮细胞（hiPSC-RPE）进行纵向成像，该方法由超微型链式金纳米颗粒簇（GNC）纳米传感器提供动力。GNC 在近红外区域表现出光吸收峰，直径为 7-8nm 后可进行肾排泄，从而提高安全性和生物相容性。在临床上相关的兔模型中，GNC 标记的 hiPSC-RPE 细胞迁移到 RPE 退化区域并再生受损组织。通过该方法，可对 hiPSC-RPE 细胞的分布和迁移进行非侵入性、纵向监测 6 个月，具有出色的灵敏度和空间分辨率。这种用于细胞成像的先进平台有可能增强基于再生细胞的治疗。
