Increasing magnetite contents of polymeric magnetic particles dramatically improves labeling of neural stem cell transplant populations

Safe and efficient delivery of therapeutic cells to sites of injury/disease in the central nervous system is a key goal for the translation of clinical cell transplantation therapies. Recently, ‘magnetic cell localization strategies' have emerged as a promising and safe approach for targeted delivery of magnetic particle (MP) labeled stem cells to pathology sites. For neuroregenerative applications, this approach is limited by the lack of available neurocompatible MPs, and low cell labeling achieved in neural stem/precursor populations. We demonstrate that high magnetite content, self-sedimenting polymeric MPs [unfunctionalized poly(lactic acid) coated, without a transfecting component] achieve efficient labeling (≥ 90%) of primary neural stem cells (NSCs)—a ‘hard-to-label’ transplant population of major clinical relevance. Our protocols showed high safety with respect to key stem cell regenerative parameters. Critically, labeled cells were effectively localized in an in vitro flow system by magnetic force highlighting the translational potential of the methods used.From the Clinical EditorUtilizing self-sedimenting polymeric magnetic particles, the authors demonstrate an efficient method for magnetically labeling primary neural stem cells for magnetic localization in the central nervous system.

Graphical AbstractThe magnetic particle (MP) platform offers several critical benefits for clinical cell therapies in regenerative neurology—for applications such as transplant cell imaging, magnetic stem cell localization and genetic modification. The low levels of MP labeling achieved in neural stem cells (NSCs—a cell population of high clinical relevance) are a major barrier to clinical translation. We demonstrate here a simple yet effective and safe method to dramatically improve NSC labeling by systematically modulating the magnetite content of polymeric, unfunctionalized MPs alone, in the absence of other particle delivery enhancing strategies.Figure optionsDownload high-quality image (142 K)Download as PowerPoint slide