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Long-term In Vivo Monitoring of Stem Cells via Magneto‐endosymbiont Labeling

Review of "Magnetic resonance imaging of human neural stem cells in rodent and primate brain" from STEM CELLS Translational Medicine by Stuart P. Atkinson

The preclinical development and translation of cell-based therapies for central nervous system disorders currently suffer from the lack of an effective means to assess graft delivery and post‐transplantation survival in vivo and a strategy for real‐time monitoring of targeting accuracy, biodistribution, and engraftment critical parameters. While magnetic resonance imaging represents a widely used modality in this sense, limitations associated with the necessary use of superparamagnetic iron oxide nanoparticles have made the long‐term longitudinal assessment of transplanted cells a challenging task.

In the search for an alternative, researchers led by Eva L. Feldman (University of Michigan, Ann Arbor, Michigan, USA) have explored the potential of novel "magneto‐endosymbiont" contrast agents derived from magnetotactic bacteria [1-3]. The high relaxivity of magneto‐endosymbiont contrast agents makes them ideal for magnetic resonance imaging [1, 2], and their potential for in vivo cell tracking by magnetic resonance imaging has recently been established in a mouse myocardial infarction model [1]. In a new STEM CELLS Translational Medicine article [4], McGinley et al. now report on the considerable potential of magneto‐endosymbiont-based imaging as a means to track human neural stem cells after intracranial injection in small and large immunocompetent animal models.

The authors reported that the stable magneto‐endosymbiont labeling of human neural stem cells, which the authors hope to develop into a novel therapy for Alzheimer's disease (See the associated STEM CELLS Translational Medicine for more) [5, 6], did not impair cell viability or interfere with therapeutically-relevant features in vitro, such as differentiation potential, paracrine activity, or neuroprotective function. In vivo analyses involved the visualization of magneto‐endosymbiont-labeled human neural stem cells by serial magnetic resonance imaging over time after intracranial xenotransplantation in both a single non-human primate and multiple model mice. The authors established correlations between magnetic resonance imaging signal, cell engraftment, and tissue magneto‐endosymbiont levels, thereby providing evidence for the potential of magneto‐endosymbiont labeling in determining graft location, volume, and targeting accuracy. Furthermore, as the findings suggest the rapid clearance of magneto‐endosymbionts from rejected grafts by the host immune response, label detection may function as an accurate indicator of cell survival after intracranial transplantation following further validation steps.

Overall, the authors suggest magneto‐endosymbionts as an accurate and non-invasive means of tracking transplanted cells in vivo and monitoring cell transplantation-based therapies; however, they also highlight the need for additional long‐term studies to further develop this unique live‐cell monitoring approach for central nervous system applications.

For more on the development of safe and effective strategies for the evaluation of graft delivery and post‐transplantation graft survival, stay tuned to the Stem Cells Portal!

References

  1. Mahmoudi M, Tachibana A, Goldstone AB, et al., Novel MRI Contrast Agent from Magnetotactic Bacteria Enables In Vivo Tracking of iPSC-derived Cardiomyocytes. Scientific Reports 2016;6:26960.
  2. Brewer KD, Spitler R, Lee KR, et al., Characterization of Magneto-Endosymbionts as MRI Cell Labeling and Tracking Agents. Molecular Imaging and Biology 2018;20:65-73.
  3. Lee KR, Wakeel A, Chakraborty P, et al., Cell Labeling with Magneto-Endosymbionts and the Dissection of the Subcellular Location, Fate, and Host Cell Interactions. Molecular Imaging and Biology 2018;20:55-64.
  4. McGinley LM, Willsey MS, Kashlan ON, et al., Magnetic resonance imaging of human neural stem cells in rodent and primate brain. STEM CELLS Translational Medicine 2021;10:83-97.
  5. McGinley LM, Kashlan ON, Chen KS, et al., Human neural stem cell transplantation into the corpus callosum of Alzheimer's mice. Annals of Clinical and Translational Neurology 2017;4:749-755.
  6. McGinley LM, Sims E, Lunn JS, et al., Human Cortical Neural Stem Cells Expressing Insulin-Like Growth Factor-I: A Novel Cellular Therapy for Alzheimer's Disease. STEM CELLS Translational Medicine 2016;5:379-391.