title: Cryopreservation of embryonic stem cell-derived multicellular neural aggregates labeled with micron-sized particles of iron oxide for magnetic resonance imaging.
abstract: Magnetic resonance imaging (MRI) provides an effective approach to track labeled pluripotent stem cell (PSC)-derived neural progenitor cells (NPCs) for neurological disorder treatments after cell labeling with a contrast agent, such as an iron oxide derivative. Cryopreservation of pre-labeled neural cells, especially in three-dimensional (3D) structure, can provide a uniform cell population and preserve the stem cell niche for the subsequent applications. In this study, the effects of cryopreservation on PSC-derived multicellular NPC aggregates labeled with micron-sized particles of iron oxide (MPIO) were investigated. These NPC aggregates were labeled prior to cryopreservation because labeling thawed cells can be limited by inefficient intracellular uptake, variations in labeling efficiency, and increased culture time before use, minimizing their translation to clinical settings. The results indicated that intracellular MPIO incorporation was retained after cryopreservation (70-80% labeling efficiency), and MPIO labeling had little adverse effects on cell recovery, proliferation, cytotoxicity and neural lineage commitment post-cryopreservation. MRI analysis showed comparable detectability for the MPIO-labeled cells before and after cryopreservation indicated by T2 and T2* relaxation rates. Cryopreserving MPIO-labeled 3D multicellular NPC aggregates can be applied in in vivo cell tracking studies and lead to more rapid translation from preservation to clinical implementation.
authors.affiliation: Dept. of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL.
authors.forename: Yuanwei
authors.initials: Y
authors.lastname: Yan
authors.forename: Sébastien
authors.initials: S
authors.lastname: Sart
authors.forename: Fabian
authors.initials: F
authors.lastname: Calixto Bejarano
authors.forename: Megan E
authors.initials: ME
authors.lastname: Muroski
authors.forename: Geoffrey F
authors.initials: GF
authors.lastname: Strouse
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Grant
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D002449:Cell Aggregation; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D015925:Cryopreservation; D053595:Embryonic Stem Cells / Q000166:cytology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D058185:Magnetite Nanoparticles; D017382:Reactive Oxygen Species
keywords: cryopreservation; iron oxide particles; neural progenitor aggregate; pluripotent stem cell