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Author Notes:

E-mail Address : ian.copland@emory.edu

We thank Shala Yuan, Jordan Murphy, and Deborah Martinson for technical assistance and the Emory Personalized Immunotherapy Center (EPIC) for providing hMSCs and platelet lysate reagents.

Subjects:

Research Funding:

This study was supported by a Georgia Cancer Coalition Award to J.G. and a Robbins Scholar Award to I.B.C.

Part of this research was performed as a project for the Immune Tolerance Network (NIH contract N01 AI15416), supported by the National Institute of Allergy and Infectious Diseases. This research project was also supported in part by the Emory University Integrated Cellular Imaging Microscopy Core of the Winship Cancer Institute comprehensive cancer center grant P30CA138292.

Actin Cytoskeletal Disruption following Cryopreservation Alters the Biodistribution of Human Mesenchymal Stromal Cells In Vivo

Journal Title:

Stem Cell Reports

Volume:

Volume 3, Number 1

Publisher:

, Pages 60-72

Type of Work:

Article | Final Publisher PDF

Abstract:

Mesenchymal stromal cells have shown clinical promise; however, variations in treatment responses are an ongoing concern. We previously demonstrated that MSCs are functionally stunned after thawing. Here, we investigated whether this cryopreservation/thawing defect also impacts the postinfusion biodistribution properties of MSCs. Under both static and physiologic flow, compared with live MSCs in active culture, MSCs thawed from cryopreservation bound poorly to fibronectin (40% reduction) and human endothelial cells (80% reduction), respectively. This reduction correlated with a reduced cytoskeletal F-actin content in post-thaw MSCs (60% reduction). In vivo, live human MSCs could be detected in murine lung tissues for up to 24 hr, whereas thawed MSCs were undetectable. Similarly, live MSCs whose actin cytoskeleton was chemically disrupted were undetectable at 24 hr postinfusion. Our data suggest that post-thaw cryopreserved MSCs are distinct from live MSCs. This distinction could significantly affect the utility of MSCs as a cellular therapeutic.

Copyright information:

© 2014 The Authors

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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