Strategies to capitalize on cell spheroid therapeutic potential for tissue repair and disease modeling

Abstract Cell therapies offer a tailorable, personalized treatment for use in tissue engineering to address defects arising from trauma, inefficient wound repair, or congenital malformation. However, most cell therapies have achieved limited success to date. Typically injected in solution as monodis...

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Main Authors: Katherine H. Griffin, Shierly W. Fok, J. Kent Leach
Format: Article
Language:English
Published: Nature Portfolio 2022-12-01
Series:npj Regenerative Medicine
Online Access:https://doi.org/10.1038/s41536-022-00266-z
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author Katherine H. Griffin
Shierly W. Fok
J. Kent Leach
author_facet Katherine H. Griffin
Shierly W. Fok
J. Kent Leach
author_sort Katherine H. Griffin
collection DOAJ
description Abstract Cell therapies offer a tailorable, personalized treatment for use in tissue engineering to address defects arising from trauma, inefficient wound repair, or congenital malformation. However, most cell therapies have achieved limited success to date. Typically injected in solution as monodispersed cells, transplanted cells exhibit rapid cell death or insufficient retention at the site, thereby limiting their intended effects to only a few days. Spheroids, which are dense, three-dimensional (3D) aggregates of cells, enhance the beneficial effects of cell therapies by increasing and prolonging cell–cell and cell–matrix signaling. The use of spheroids is currently under investigation for many cell types. Among cells under evaluation, spheroids formed of mesenchymal stromal cells (MSCs) are particularly promising. MSC spheroids not only exhibit increased cell survival and retained differentiation, but they also secrete a potent secretome that promotes angiogenesis, reduces inflammation, and attracts endogenous host cells to promote tissue regeneration and repair. However, the clinical translation of spheroids has lagged behind promising preclinical outcomes due to hurdles in their formation, instruction, and use that have yet to be overcome. This review will describe the current state of preclinical spheroid research and highlight two key examples of spheroid use in clinically relevant disease modeling. It will highlight techniques used to instruct the phenotype and function of spheroids, describe current limitations to their use, and offer suggestions for the effective translation of cell spheroids for therapeutic treatments.
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spelling doaj.art-ebbd594b28354174b1d3e1fb8c8805602022-12-22T03:50:45ZengNature Portfolionpj Regenerative Medicine2057-39952022-12-017111310.1038/s41536-022-00266-zStrategies to capitalize on cell spheroid therapeutic potential for tissue repair and disease modelingKatherine H. Griffin0Shierly W. Fok1J. Kent Leach2Department of Orthopaedic Surgery, UC Davis HealthDepartment of Orthopaedic Surgery, UC Davis HealthDepartment of Orthopaedic Surgery, UC Davis HealthAbstract Cell therapies offer a tailorable, personalized treatment for use in tissue engineering to address defects arising from trauma, inefficient wound repair, or congenital malformation. However, most cell therapies have achieved limited success to date. Typically injected in solution as monodispersed cells, transplanted cells exhibit rapid cell death or insufficient retention at the site, thereby limiting their intended effects to only a few days. Spheroids, which are dense, three-dimensional (3D) aggregates of cells, enhance the beneficial effects of cell therapies by increasing and prolonging cell–cell and cell–matrix signaling. The use of spheroids is currently under investigation for many cell types. Among cells under evaluation, spheroids formed of mesenchymal stromal cells (MSCs) are particularly promising. MSC spheroids not only exhibit increased cell survival and retained differentiation, but they also secrete a potent secretome that promotes angiogenesis, reduces inflammation, and attracts endogenous host cells to promote tissue regeneration and repair. However, the clinical translation of spheroids has lagged behind promising preclinical outcomes due to hurdles in their formation, instruction, and use that have yet to be overcome. This review will describe the current state of preclinical spheroid research and highlight two key examples of spheroid use in clinically relevant disease modeling. It will highlight techniques used to instruct the phenotype and function of spheroids, describe current limitations to their use, and offer suggestions for the effective translation of cell spheroids for therapeutic treatments.https://doi.org/10.1038/s41536-022-00266-z
spellingShingle Katherine H. Griffin
Shierly W. Fok
J. Kent Leach
Strategies to capitalize on cell spheroid therapeutic potential for tissue repair and disease modeling
npj Regenerative Medicine
title Strategies to capitalize on cell spheroid therapeutic potential for tissue repair and disease modeling
title_full Strategies to capitalize on cell spheroid therapeutic potential for tissue repair and disease modeling
title_fullStr Strategies to capitalize on cell spheroid therapeutic potential for tissue repair and disease modeling
title_full_unstemmed Strategies to capitalize on cell spheroid therapeutic potential for tissue repair and disease modeling
title_short Strategies to capitalize on cell spheroid therapeutic potential for tissue repair and disease modeling
title_sort strategies to capitalize on cell spheroid therapeutic potential for tissue repair and disease modeling
url https://doi.org/10.1038/s41536-022-00266-z
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