Novel surface-enhanced Raman scattering-based assays for ultra-sensitive detection of human pluripotent stem cells

• Type of Material: Article
• Authors: Jingjia Han, Emory University; Ximei Qian, Emory University; Qingling Wu, Emory University; Rajneesh Jha, Emory University; Jinshuai Duan, University of Science and Technology Beijing; Zhou Yang, University of Science and Technology Beijing; Kevin Maher, Emory University; Shuming Nie, Emory University; Chunhui Xu, Emory University
• Language: English
• Date: 2016-10-01
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2016 The Authors.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.biomaterials.2016.07.033
• Title of Journal or Parent Work: Biomaterials
• ISSN: 0142-9612
• Volume: 105
• Start Page: 66
• End Page: 76
• Grant/Funding Information: This project was supported in part by the Center for Pediatric Nanomedicine at the Emory • Children’s • GT Pediatric Research Alliance, the NIH grant R21HL123928 to C.X, a grant No. 51373024 to Z. Y. from the National Natural Science Foundation of China, and a seed grant to C.X. from the National Center for Advancing Translational Sciences of the NIH under Award Number UL1TR000454.
• Keywords: SERS assay; Flow cytometry; Nanoparticle; Human pluripotent stem cell; Differentiation
• Research Categories: Engineering, Biomedical; Health Sciences, General

Abstract

Human pluripotent stem cells (hPSCs) are a promising cell source for regenerative medicine, but their derivatives need to be rigorously evaluated for residual stem cells to prevent teratoma formation. Here, we report the development of novel surface-enhanced Raman scattering (SERS)-based assays that can detect trace numbers of undifferentiated hPSCs in mixed cell populations in a highly specific, ultra-sensitive, and time-efficient manner. By targeting stem cell surface markers SSEA-5 and TRA-1-60 individually or simultaneously, these SERS assays were able to identify as few as 1 stem cell in 106 cells, a sensitivity (0.0001%) which was ∼2000 to 15,000-fold higher than that of flow cytometry assays. Using the SERS assay, we demonstrate that the aggregation of hPSC-based cardiomyocyte differentiation cultures into 3D spheres significantly reduced SSEA-5+ and TRA-1-60+ cells compared with parallel 2D cultures. Thus, SERS may provide a powerful new technology for quality control of hPSC-derived products for preclinical and clinical applications.