title: Actin cytoskeletal disruption following cryopreservation alters the biodistribution of human mesenchymal stromal cells in vivo.
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.
authors: Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA ; Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
authors: Raghavan
authors: R
authors: Chinnadurai
authors: Emory Healthcare, Atlanta, GA 30322, USA.
authors: Marco A
authors: MA
authors: Garcia
authors: Department of Pediatrics, Emory University, Atlanta, GA 30322, USA ; Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory University, Atlanta, GA 30322, USA.
authors: Yumiko
authors: Y
authors: Sakurai
authors: Department of Pediatrics, Emory University, Atlanta, GA 30322, USA ; Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory University, Atlanta, GA 30322, USA.
authors: Wilbur A
authors: WA
authors: Lam
authors: Department of Surgery, Division of Transplantation, Emory University School of Medicine, Atlanta, GA 30322, USA ; Emory Transplant Center, Emory University, Atlanta, GA 30322, USA.
authors: Allan D
authors: AD
authors: Kirk
authors: Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA ; Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA ; Department of Pediatrics, Emory University, Atlanta, GA 30322, USA ; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.
authors: Jacques
authors: J
authors: Galipeau
authors: Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA ; Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
authors: Ian B
authors: IB
authors: Copland
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D015925:Cryopreservation; D003599:Cytoskeleton / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000199:Actins