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Delivery strategies for cell-based therapies in the brain: overcoming multiple barriers

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Abstract

Cell-based therapies to the brain are promising for the treatment of multiple brain disorders including neurodegeneration and cancers. In order to access the brain parenchyma, there are multiple physiological barriers that must be overcome depending on the route of delivery. Specifically, the blood–brain barrier has been a major difficulty in drug delivery for decades, and it still presents a challenge for the delivery of therapeutic cells. Other barriers, including the blood-cerebrospinal fluid barrier and lymphatic-brain barrier, are less explored, but may offer specific challenges or opportunities for therapeutic delivery. Here we discuss the barriers to the brain and the strategies currently in place to deliver cell-based therapies, including engineered T cells, dendritic cells, and stem cells, to treat diseases. With a particular focus on cancers, we also highlight the current ongoing clinical trials that use cell-based therapies to treat disease, many of which show promise at treating some of the deadliest illnesses.

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Acknowledgements

Figures were created using Biorender with a license to JMM.

Funding

Funding provided to JMM from the National Cancer Institute R37CA222563. Funding provided to JMM, RCR, and CEB from the National Institute of Neurological Disorders and Stroke R01NS115971. Funding for OMT from the National Institute of General Medical Sciences R25GM066534 to Ed Smith.

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  1. Fralin Biomedical Research Institute, Virginia Polytechnic Institute and State University, Roanoke, VA, USA

    Olivia M. Turk & Jennifer M. Munson

  2. Department of Computational and Quantitative Medicine, Division of Mathematical Oncology, City of Hope, Duarte, CA, USA

    Ryan C. Woodall & Russell C. Rockne

  3. Departments of Hematology & Hematopoietic Cell Transplantation and Immuno-Oncology, City of Hope, Duarte, CA, USA

    Christine E. Brown

  4. Department of Stem Cell Biology and Regenerative Medicine, City of Hope, Duarte, CA, USA

    Margarita Gutova

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Turk, O.M., Woodall, R.C., Gutova, M. et al. Delivery strategies for cell-based therapies in the brain: overcoming multiple barriers. Drug Deliv. and Transl. Res. 11, 2448–2467 (2021). https://doi.org/10.1007/s13346-021-01079-1

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