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Editing a gateway for cell therapy across the blood–brain barrier

Stem cell therapy has been shown to improve stroke outcomes in animal models and is currently advancing towards clinical practice. However, uncertainty remains regarding the optimal route for cell delivery to the injured brain. Local intracerebral injections are effective in precisely delivering cel...

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Detalles Bibliográficos
Autores principales: Achón Buil, Beatriz, Tackenberg, Christian, Rust, Ruslan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9976985/
https://www.ncbi.nlm.nih.gov/pubmed/36397727
http://dx.doi.org/10.1093/brain/awac393
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author Achón Buil, Beatriz
Tackenberg, Christian
Rust, Ruslan
author_facet Achón Buil, Beatriz
Tackenberg, Christian
Rust, Ruslan
author_sort Achón Buil, Beatriz
collection PubMed
description Stem cell therapy has been shown to improve stroke outcomes in animal models and is currently advancing towards clinical practice. However, uncertainty remains regarding the optimal route for cell delivery to the injured brain. Local intracerebral injections are effective in precisely delivering cells into the stroke cavity but carry the risk of damaging adjacent healthy tissue. Systemic endovascular injections, meanwhile, are minimally invasive, but most injected cells do not cross CNS barriers and become mechanically trapped in peripheral organs. Although the blood–brain barrier and the blood–CSF barrier tightly limit the entrance of cells and molecules into the brain parenchyma, immune cells can cross these barriers especially under pathological conditions, such as stroke. Deciphering the cell surface signature and the molecular mechanisms underlying this pathophysiological process holds promise for improving the targeted delivery of systemic injected cells to the injured brain. In this review, we describe experimental approaches that have already been developed in which (i) cells are either engineered to express cell surface proteins mimicking infiltrating immune cells; or (ii) cell grafts are preconditioned with hypoxia or incubated with pharmacological agents or cytokines. Modified cell grafts can be complemented with strategies to temporarily increase the permeability of the blood–brain barrier. Although these approaches could significantly enhance homing of stem cells into the injured brain, cell entrapment in off-target organs remains a non-negligible risk. Recent developments in safety-switch systems, which enable the precise elimination of transplanted cells on the administration of a drug, represent a promising strategy for selectively removing stem cells stuck in untargeted organs. In sum, the techniques described in this review hold great potential to substantially improve efficacy and safety of future cell therapies in stroke and may be relevant to other brain diseases.
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spelling pubmed-99769852023-03-02 Editing a gateway for cell therapy across the blood–brain barrier Achón Buil, Beatriz Tackenberg, Christian Rust, Ruslan Brain Review Article Stem cell therapy has been shown to improve stroke outcomes in animal models and is currently advancing towards clinical practice. However, uncertainty remains regarding the optimal route for cell delivery to the injured brain. Local intracerebral injections are effective in precisely delivering cells into the stroke cavity but carry the risk of damaging adjacent healthy tissue. Systemic endovascular injections, meanwhile, are minimally invasive, but most injected cells do not cross CNS barriers and become mechanically trapped in peripheral organs. Although the blood–brain barrier and the blood–CSF barrier tightly limit the entrance of cells and molecules into the brain parenchyma, immune cells can cross these barriers especially under pathological conditions, such as stroke. Deciphering the cell surface signature and the molecular mechanisms underlying this pathophysiological process holds promise for improving the targeted delivery of systemic injected cells to the injured brain. In this review, we describe experimental approaches that have already been developed in which (i) cells are either engineered to express cell surface proteins mimicking infiltrating immune cells; or (ii) cell grafts are preconditioned with hypoxia or incubated with pharmacological agents or cytokines. Modified cell grafts can be complemented with strategies to temporarily increase the permeability of the blood–brain barrier. Although these approaches could significantly enhance homing of stem cells into the injured brain, cell entrapment in off-target organs remains a non-negligible risk. Recent developments in safety-switch systems, which enable the precise elimination of transplanted cells on the administration of a drug, represent a promising strategy for selectively removing stem cells stuck in untargeted organs. In sum, the techniques described in this review hold great potential to substantially improve efficacy and safety of future cell therapies in stroke and may be relevant to other brain diseases. Oxford University Press 2022-11-18 /pmc/articles/PMC9976985/ /pubmed/36397727 http://dx.doi.org/10.1093/brain/awac393 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Review Article
Achón Buil, Beatriz
Tackenberg, Christian
Rust, Ruslan
Editing a gateway for cell therapy across the blood–brain barrier
title Editing a gateway for cell therapy across the blood–brain barrier
title_full Editing a gateway for cell therapy across the blood–brain barrier
title_fullStr Editing a gateway for cell therapy across the blood–brain barrier
title_full_unstemmed Editing a gateway for cell therapy across the blood–brain barrier
title_short Editing a gateway for cell therapy across the blood–brain barrier
title_sort editing a gateway for cell therapy across the blood–brain barrier
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9976985/
https://www.ncbi.nlm.nih.gov/pubmed/36397727
http://dx.doi.org/10.1093/brain/awac393
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