title: Cryopreserved Mesenchymal Stromal Cells Maintain Potency in a Retinal Ischemia/Reperfusion Injury Model: Toward an off-the-shelf Therapy.
abstract: The ability to use mesenchymal stromal cells (MSC) directly out of cryostorage would significantly reduce the logistics of MSC therapy by allowing on-site cryostorage of therapeutic doses of MSC at hospitals and clinics. Such a paradigm would be especially advantageous for the treatment of acute conditions such as stroke and myocardial infarction, which are likely to require treatment within hours after ischemic onset. Recently, several reports have emerged that suggest MSC viability and potency are damaged by cryopreservation. Herein we examine the effect of cryopreservation on human MSC viability, immunomodulatory potency, growth factor secretion, and performance in an ischemia/reperfusion injury model. Using modifications of established cryopreservation methods we developed MSC that retain >95% viability upon thawing, remain responsive to inflammatory signals, and are able to suppress activated human peripheral blood mononuclear cells. Most importantly, when injected into the eyes of mice 3 hours after the onset of ischemia and 2 hours after the onset of reperfusion, cryopreserved performed as well as fresh MSC to rescue retinal ganglion cells. Thus, our data suggests when viability is maintained throughout the cryopreservation process, MSC retain their therapeutic potency in both in vitro potency assays and an in vivo ischemia/reperfusion model.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA, USA.|Center for the Prevention and Treatment of Visual Loss, Iowa City VA Health Care, Iowa City, IA, USA.
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Gramlich
authors.affiliation: Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA.|Fraternal Order of Eagles Diabetes Research Center, Pappajohn Biomedical Institute, University of Iowa, Iowa City, IA, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Burand
authors.affiliation: Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA.|Fraternal Order of Eagles Diabetes Research Center, Pappajohn Biomedical Institute, University of Iowa, Iowa City, IA, USA.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Brown
authors.affiliation: Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA.|Fraternal Order of Eagles Diabetes Research Center, Pappajohn Biomedical Institute, University of Iowa, Iowa City, IA, USA.
authors.forename: Riley J
authors.initials: RJ
authors.lastname: Deutsch
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA, USA.|Center for the Prevention and Treatment of Visual Loss, Iowa City VA Health Care, Iowa City, IA, USA.
authors.forename: Markus H
authors.initials: MH
authors.lastname: Kuehn
authors.affiliation: Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA.|Fraternal Order of Eagles Diabetes Research Center, Pappajohn Biomedical Institute, University of Iowa, Iowa City, IA, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Ankrum
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D015925:Cryopreservation / Q000379:methods*; D004195:Disease Models, Animal; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D015427:Reperfusion Injury / Q000628:therapy*; D012164:Retinal Diseases / Q000628:therapy*; D012165:Retinal Ganglion Cells / Q000166:cytology