Magnetic resonance imaging of human neural stem cells in rodent and primate brain

Author:

McGinley Lisa M.1,Willsey Matthew S.23,Kashlan Osama N.12,Chen Kevin S.12,Hayes John M.1,Bergin Ingrid L.4,Mason Shayna N.1,Stebbins Aaron W.1,Kwentus Jacquelin F.1,Pacut Crystal1,Kollmer Jennifer5,Sakowski Stacey A.1,Bell Caleb B.67,Chestek Cynthia A.389,Murphy Geoffrey G.1011,Patil Parag G.123,Feldman Eva L.1

Affiliation:

1. Department of Neurology University of Michigan, Ann Arbor, Michigan, USA

2. Department of Neurosurgery University of Michigan, Ann Arbor, Michigan, USA

3. Department of Biomedical Engineering University of Michigan, Ann Arbor, Michigan, USA

4. Unit for Laboratory Animal Medicine University of Michigan, Ann Arbor, Michigan, USA

5. Department of Neuroradiology University Hospital Heidelberg, Heidelberg, Germany

6. Bell Biosystems, San Francisco, California, USA

7. G4S Capital & Ikigai Accelerator, Santa Clara, California, USA

8. Department of Electrical Engineering University of Michigan, Ann Arbor, Michigan, USA

9. Neuroscience and Robotics Graduate Program University of Michigan, Ann Arbor, Michigan, USA

10. Department of Molecular and Integrative Physiology University of Michigan, Ann Arbor, Michigan, USA

11. Molecular and Behavioral Neuroscience Institute University of Michigan, Ann Arbor, Michigan, USA

Abstract

Abstract Stem cell transplantation therapies are currently under investigation for central nervous system disorders. Although preclinical models show benefit, clinical translation is somewhat limited by the absence of reliable noninvasive methods to confirm targeting and monitor transplanted cells in vivo. Here, we assess a novel magnetic resonance imaging (MRI) contrast agent derived from magnetotactic bacteria, magneto-endosymbionts (MEs), as a translatable methodology for in vivo tracking of stem cells after intracranial transplantation. We show that ME labeling provides robust MRI contrast without impairment of cell viability or other important therapeutic features. Labeled cells were visualized immediately post-transplantation and over time by serial MRI in nonhuman primate and mouse brain. Postmortem tissue analysis confirmed on-target grft location, and linear correlations were observed between MRI signal, cell engraftment, and tissue ME levels, suggesting that MEs may be useful for determining graft survival or rejection. Overall, these findings indicate that MEs are an effective tool for in vivo tracking and monitoring of cell transplantation therapies with potential relevance to many cellular therapy applications.

Funder

Comprehensive Cancer Center NIH

NIDDK

Sinai Medical Staff Foundation

Robert E. Nederlander Sr. Program for Alzheimer's Research

NeuroNetwork for Emerging Therapies

Handleman Emerging Scholar Program

A. Alfred Taubman Medical Research Institute

National Institutes of Health

National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,General Medicine

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