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Single-cell sorting based on secreted products for functionally defined cell therapies
Cell therapies have emerged as a promising new class of “living” therapeutics over the last decade and have been particularly successful for treating hematological malignancies. Increasingly, cellular therapeutics are being developed with the aim of treating almost any disease, from solid tumors and...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303846/ https://www.ncbi.nlm.nih.gov/pubmed/35874174 http://dx.doi.org/10.1038/s41378-022-00422-x |
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author | Miwa, Hiromi Dimatteo, Robert de Rutte, Joseph Ghosh, Rajesh Di Carlo, Dino |
author_facet | Miwa, Hiromi Dimatteo, Robert de Rutte, Joseph Ghosh, Rajesh Di Carlo, Dino |
author_sort | Miwa, Hiromi |
collection | PubMed |
description | Cell therapies have emerged as a promising new class of “living” therapeutics over the last decade and have been particularly successful for treating hematological malignancies. Increasingly, cellular therapeutics are being developed with the aim of treating almost any disease, from solid tumors and autoimmune disorders to fibrosis, neurodegenerative disorders and even aging itself. However, their therapeutic potential has remained limited due to the fundamental differences in how molecular and cellular therapies function. While the structure of a molecular therapeutic is directly linked to biological function, cells with the same genetic blueprint can have vastly different functional properties (e.g., secretion, proliferation, cell killing, migration). Although there exists a vast array of analytical and preparative separation approaches for molecules, the functional differences among cells are exacerbated by a lack of functional potency-based sorting approaches. In this context, we describe the need for next-generation single-cell profiling microtechnologies that allow the direct evaluation and sorting of single cells based on functional properties, with a focus on secreted molecules, which are critical for the in vivo efficacy of current cell therapies. We first define three critical processes for single-cell secretion-based profiling technology: (1) partitioning individual cells into uniform compartments; (2) accumulating secretions and labeling via reporter molecules; and (3) measuring the signal associated with the reporter and, if sorting, triggering a sorting event based on these reporter signals. We summarize recent academic and commercial technologies for functional single-cell analysis in addition to sorting and industrial applications of these technologies. These approaches fall into three categories: microchamber, microfluidic droplet, and lab-on-a-particle technologies. Finally, we outline a number of unmet needs in terms of the discovery, design and manufacturing of cellular therapeutics and how the next generation of single-cell functional screening technologies could allow the realization of robust cellular therapeutics for all patients. |
format | Online Article Text |
id | pubmed-9303846 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-93038462022-07-22 Single-cell sorting based on secreted products for functionally defined cell therapies Miwa, Hiromi Dimatteo, Robert de Rutte, Joseph Ghosh, Rajesh Di Carlo, Dino Microsyst Nanoeng Review Article Cell therapies have emerged as a promising new class of “living” therapeutics over the last decade and have been particularly successful for treating hematological malignancies. Increasingly, cellular therapeutics are being developed with the aim of treating almost any disease, from solid tumors and autoimmune disorders to fibrosis, neurodegenerative disorders and even aging itself. However, their therapeutic potential has remained limited due to the fundamental differences in how molecular and cellular therapies function. While the structure of a molecular therapeutic is directly linked to biological function, cells with the same genetic blueprint can have vastly different functional properties (e.g., secretion, proliferation, cell killing, migration). Although there exists a vast array of analytical and preparative separation approaches for molecules, the functional differences among cells are exacerbated by a lack of functional potency-based sorting approaches. In this context, we describe the need for next-generation single-cell profiling microtechnologies that allow the direct evaluation and sorting of single cells based on functional properties, with a focus on secreted molecules, which are critical for the in vivo efficacy of current cell therapies. We first define three critical processes for single-cell secretion-based profiling technology: (1) partitioning individual cells into uniform compartments; (2) accumulating secretions and labeling via reporter molecules; and (3) measuring the signal associated with the reporter and, if sorting, triggering a sorting event based on these reporter signals. We summarize recent academic and commercial technologies for functional single-cell analysis in addition to sorting and industrial applications of these technologies. These approaches fall into three categories: microchamber, microfluidic droplet, and lab-on-a-particle technologies. Finally, we outline a number of unmet needs in terms of the discovery, design and manufacturing of cellular therapeutics and how the next generation of single-cell functional screening technologies could allow the realization of robust cellular therapeutics for all patients. Nature Publishing Group UK 2022-07-22 /pmc/articles/PMC9303846/ /pubmed/35874174 http://dx.doi.org/10.1038/s41378-022-00422-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Article Miwa, Hiromi Dimatteo, Robert de Rutte, Joseph Ghosh, Rajesh Di Carlo, Dino Single-cell sorting based on secreted products for functionally defined cell therapies |
title | Single-cell sorting based on secreted products for functionally defined cell therapies |
title_full | Single-cell sorting based on secreted products for functionally defined cell therapies |
title_fullStr | Single-cell sorting based on secreted products for functionally defined cell therapies |
title_full_unstemmed | Single-cell sorting based on secreted products for functionally defined cell therapies |
title_short | Single-cell sorting based on secreted products for functionally defined cell therapies |
title_sort | single-cell sorting based on secreted products for functionally defined cell therapies |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303846/ https://www.ncbi.nlm.nih.gov/pubmed/35874174 http://dx.doi.org/10.1038/s41378-022-00422-x |
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