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Nat Commun. 2016 Jun 21;7:11945. doi: 10.1038/ncomms11945.

Microfluidic single-cell transcriptional analysis rationally identifies novel surface marker profiles to enhance cell-based therapies.

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Department of Surgery, Hagey Laboratory for Pediatric Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Program in Biomedical Informatics, Stanford University School of Medicine, Stanford, California 94305, USA.
Section of Plastic, Aesthetic and Reconstructive Surgery, Johannes Kepler University, Linz, Austria.
Department of Plastic Surgery and Hand Surgery, Technical University Munich, Munich, Germany.
The University of Melbourne Department of Surgery, Royal Melbourne Hospital, 300 Grattan St Parkville VIC 3068, Australia.
Department of Pediatrics, Division of Systems Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.


Current progenitor cell therapies have only modest efficacy, which has limited their clinical adoption. This may be the result of a cellular heterogeneity that decreases the number of functional progenitors delivered to diseased tissue, and prevents correction of underlying pathologic cell population disruptions. Here, we develop a high-resolution method of identifying phenotypically distinct progenitor cell subpopulations via single-cell transcriptional analysis and advanced bioinformatics. When combined with high-throughput cell surface marker screening, this approach facilitates the rational selection of surface markers for prospective isolation of cell subpopulations with desired transcriptional profiles. We establish the usefulness of this platform in costly and highly morbid diabetic wounds by identifying a subpopulation of progenitor cells that is dysfunctional in the diabetic state, and normalizes diabetic wound healing rates following allogeneic application. We believe this work presents a logical framework for the development of targeted cell therapies that can be customized to any clinical application.

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