Cellular imaging DOI: 10.1002/smll.200700493 Mesoporous Silica Nanoparticles Improve Magnetic Labeling Efficiency in Human Stem Cells Hon-Man Liu, y Si-Han Wu, y Chen-Wen Lu, Ming Yao, Jong-Kai Hsiao, Yann Hung, Yu-Shen Lin, Chung-Yuan Mou, Chung-Shi Yang, Dong-Ming Huang, * and Yao-Chang Chen Tumblerlike magnetic/fluorescein isothiocyanate (FITC)-labeled mesoporous silica nanoparticles, Mag-Dye@MSNs, have been developed, which are composed of silica-coated core–shell superparamagnetic iron oxide (SPIO@SiO 2 ) nanoparticles co-condensed with FITC-incorporated mesoporous silica. Mag-Dye@MSNs can label human mesenchymal stem cells (hMSCs) through endocytosis efficiently for magnetic resonance imaging (MRI) in vitro and in vivo, as manifested by using a clinical 1.5-T MRI system with requirements of simultaneous low incubation dosage of iron, low detection cell numbers, and short incubation time. Labeled hMSCs are unaffected in their viability, proliferation, and differentiation capacities into adipocytes and osteocytes, which can still be readily detected by MRI. Moreover, a higher MRI signal intensity decrease is observed in Mag- Dye@MSN-treated cells than in SPIO@SiO 2 -treated cells. This is the first report that MCM-41-type MSNs are advantageous to cellular uptake, as manifested by a higher labeling efficiency of Mag-Dye@MSNs than SPIO@SiO 2 . 1. Introduction Tracking the distribution of stem cells in vivo for distinguishing whether cellular regeneration originated from an exogenous cell source is crucial to their therapeutic use. Traditionally, the techniques for examining stem-cell trans- plantation in animal models are performed by postmortem histological analysis and consequently cannot be applied in clinical studies. Thus, the development of techniques to noninvasively monitor the fate and distribution of transplanted stem cells is definitely important and has attracted great research efforts. Among these, magnetic resonance imaging (MRI) is an ideal imaging modality for the biodistribution of magnetically labeled cells. [1–3] To track stem cells by MRI, cells must be labeled magnetically by endocytic internalization. [3–5] However, cellular tracking by these nanoparticles suffers from low intracellular labeling efficiency, as manifested by the requirement of a long-term incubation or a high concentration [  ] C.-W. Lu, Dr. C.-S. Yang, Dr. D.-M. Huang Center for Nanomedicine Research National Health Research Institutes 35 Keyan Rd., Zhunan Town, Miaoli County 350 (Taiwan) E-mail: dmhuang@nhri.org.tw Dr. H.-M. Liu, y Dr. J.-K. Hsiao Department of Medical Imaging National Taiwan University Hospital and College of Medicine National Taiwan University 7 Chung-Shan South Rd. Taipei 100 (Taiwan) S.-H. Wu, y Dr. Y. Hung, Y.-S. Lin, Dr. C.-Y. Mou Department of Chemistry National Taiwan University 1 Sec. 4, Roosevelt Rd. Taipei 106 (Taiwan) Dr. M. Yao, Dr. Y.-C. Chen Department of Laboratory Medicine National Taiwan University Hospital and College of Medicine National Taiwan University 7 Chung-Shan South Rd. Taipei 100 (Taiwan) [ y ] These authors contributed equally to this work. : Supporting Information is available on the WWW under http:// www.small-journal.com or from the author. Keywords:  biocompatible materials  magnetic resonance imaging  mesoporous materials  nanoparticles  stem cells small 2008, 4, No. 5, 619–626 ß 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 619