Cryopreserved Mesenchymal Stromal Cells Maintain Potency in a Retinal Ischemia/Reperfusion Injury Model: Toward an off-the-shelf Therapy

Oliver W Gramlich; Anthony J Burand; Alex J Brown; Riley J Deutsch; Markus H Kuehn; James A Ankrum

doi:10.1038/srep26463

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Cryopreserved Mesenchymal Stromal Cells Maintain Potency in a Retinal Ischemia/Reperfusion Injury Model: Toward an off-the-shelf Therapy

Journal article

Open access

Peer reviewed

Cryopreserved Mesenchymal Stromal Cells Maintain Potency in a Retinal Ischemia/Reperfusion Injury Model: Toward an off-the-shelf Therapy

Oliver W Gramlich, Anthony J Burand, Alex J Brown, Riley J Deutsch, Markus H Kuehn and James A Ankrum

Scientific reports, Vol.6(1), 26463

05/23/2016

DOI: 10.1038/srep26463

PMCID: PMC4876464

PMID: 27212469

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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.

Reperfusion Injury - therapy

Cell Proliferation

Cell Survival

Humans

Cells, Cultured

Retinal Diseases - therapy

Cryopreservation - methods

Mesenchymal Stem Cell Transplantation - methods

Retinal Ganglion Cells - cytology

Animals

Mesenchymal Stem Cells - cytology

Mice

Disease Models, Animal

Details

Title: Subtitle: Cryopreserved Mesenchymal Stromal Cells Maintain Potency in a Retinal Ischemia/Reperfusion Injury Model: Toward an off-the-shelf Therapy
Creators: Oliver W Gramlich - University of Iowa, University of Iowa Health Care
Anthony J Burand - University of Iowa
Alex J Brown - University of Iowa
Riley J Deutsch - University of Iowa
Markus H Kuehn - University of Iowa
James A Ankrum - University of Iowa, Pappajohn Biomedical Institute
Resource Type: Journal article
Publication Details: Scientific reports, Vol.6(1), 26463
DOI: 10.1038/srep26463
PMID: 27212469
PMCID: PMC4876464
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: England
Grant note: U24 DK076169 / NIDDK NIH HHS I01 RX001163 / RRD VA P30 EY025580 / NEI NIH HHS I50 RX003002 / RRD VA
Language: English
Date published: 05/23/2016
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983980055302771

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