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First published online May 10, 2007
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2006-0722v1
25/8/2128    most recent
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Submitted on November 8, 2006
Accepted on May 4, 2007

TECHNOLOGY DEVELOPMENT

Finding Fluorescent Needles in the Cardiac Haystack: Tracking Human Mesenchymal Stem Cells Labeled with Quantum Dots for Quantitative In Vivo 3-D Fluorescence Analysis

Amy B. Rosen 1*, Damon J. Kelly 2, Adam J. T. Schuldt 1, Jia Lu 2, Irina A. Potapova 2, Sergey V. Doronin 2, Kyle J. Robichaud 3, Richard B. Robinson 4, Michael R. Rosen 5, Peter R. Brink 2, Glenn R. Gaudette 3, Ira S. Cohen 6

1 Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York 11794, USA; Institute for Molecular Cardiology, State University of New York at Stony Brook, Stony Brook, New York 11794, USA
2 Department of Physiology and Biophysics, State University of New York at Stony Brook, Stony Brook, New York 11794, USA; Institute for Molecular Cardiology, State University of New York at Stony Brook, Stony Brook, New York 11794, USA
3 Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA 01655 USA
4 Department of Pharmacology, Columbia University, New York, New York, 10032, USA; Center for Molecular Therapeutics, Columbia University, New York, New York, 10032, USA
5 Department of Pharmacology, Columbia University, New York, New York, 10032, USA; Institute for Molecular Cardiology, State University of New York at Stony Brook, Stony Brook, New York 11794, USA; Center for Molecular Therapeutics, Columbia University, New York, New York, 10032, USA
6 Department of Physiology and Biophysics, State University of New York at Stony Brook, Stony Brook, New York 11794, USA; Institute for Molecular Cardiology, State University of New York at Stony Brook, Stony Brook, New York 11794, USA; Center for Molecular Therapeutics, Columbia University, New York, New York, 10032, USA

* To whom correspondence should be addressed. E-mail: amybrosen{at}gmail.com.


   Abstract

Stem cells show promise for repair of damaged cardiac tissue. Little is known with certainty, however, about the distribution of these cells once introduced in vivo. Previous attempts at tracking delivered stem cells have been hampered by the autofluorescence of host tissue and limitations of existing labeling techniques. We have developed a novel loading approach to stably label human mesenchymal stem cells (hMSCs) with quantum dot (QD) nanoparticles. We report the optimization and validation of this long-term tracking technique and highlight several important biological applications by delivering labeled cells to the mammalian heart. The bright QD crystals illuminate exogenous stem cells in histologic sections for at least 8 weeks following delivery and permit for the first time, the complete 3-D reconstruction of the locations of all stem cells following injection into the heart.

Key Words. human mesenchymal stem cells (hMSCs), cell labeling, cell tracking, nanotechnology, imaging




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