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Spheroid Culture of Mesenchymal Stromal Cells Results in Morphorheological Properties Appropriate for Improved Microcirculation

Human bone marrow mesenchymal stromal cells (MSCs) are used in clinical trials for the treatment of systemic inflammatory diseases due to their regenerative and immunomodulatory properties. However, intravenous administration of MSCs is hampered by cell trapping within the pulmonary capillary networ...

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Autores principales: Tietze, Stefanie, Kräter, Martin, Jacobi, Angela, Taubenberger, Anna, Herbig, Maik, Wehner, Rebekka, Schmitz, Marc, Otto, Oliver, List, Catrin, Kaya, Berna, Wobus, Manja, Bornhäuser, Martin, Guck, Jochen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469243/
https://www.ncbi.nlm.nih.gov/pubmed/31016116
http://dx.doi.org/10.1002/advs.201802104
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author Tietze, Stefanie
Kräter, Martin
Jacobi, Angela
Taubenberger, Anna
Herbig, Maik
Wehner, Rebekka
Schmitz, Marc
Otto, Oliver
List, Catrin
Kaya, Berna
Wobus, Manja
Bornhäuser, Martin
Guck, Jochen
author_facet Tietze, Stefanie
Kräter, Martin
Jacobi, Angela
Taubenberger, Anna
Herbig, Maik
Wehner, Rebekka
Schmitz, Marc
Otto, Oliver
List, Catrin
Kaya, Berna
Wobus, Manja
Bornhäuser, Martin
Guck, Jochen
author_sort Tietze, Stefanie
collection PubMed
description Human bone marrow mesenchymal stromal cells (MSCs) are used in clinical trials for the treatment of systemic inflammatory diseases due to their regenerative and immunomodulatory properties. However, intravenous administration of MSCs is hampered by cell trapping within the pulmonary capillary networks. Here, it is hypothesized that traditional 2D plastic‐adherent cell expansion fails to result in appropriate morphorheological properties required for successful cell circulation. To address this issue, a method to culture MSCs in nonadherent 3D spheroids (mesenspheres) is adapted. The biological properties of mesensphere‐cultured MSCs remain identical to conventional 2D cultures. However, morphorheological analyses reveal a smaller size and lower stiffness of mesensphere‐derived MSCs compared to plastic‐adherent MSCs, measured using real‐time deformability cytometry and atomic force microscopy. These properties result in an increased ability to pass through microconstrictions in an ex vivo microcirculation assay. This ability is confirmed in vivo by comparison of cell accumulation in various organ capillary networks after intravenous injection of both types of MSCs in mouse. The findings generally identify cellular morphorheological properties as attractive targets for improving microcirculation and specifically suggest mesensphere culture as a promising approach for optimized MSC‐based therapies.
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spelling pubmed-64692432019-04-23 Spheroid Culture of Mesenchymal Stromal Cells Results in Morphorheological Properties Appropriate for Improved Microcirculation Tietze, Stefanie Kräter, Martin Jacobi, Angela Taubenberger, Anna Herbig, Maik Wehner, Rebekka Schmitz, Marc Otto, Oliver List, Catrin Kaya, Berna Wobus, Manja Bornhäuser, Martin Guck, Jochen Adv Sci (Weinh) Full Papers Human bone marrow mesenchymal stromal cells (MSCs) are used in clinical trials for the treatment of systemic inflammatory diseases due to their regenerative and immunomodulatory properties. However, intravenous administration of MSCs is hampered by cell trapping within the pulmonary capillary networks. Here, it is hypothesized that traditional 2D plastic‐adherent cell expansion fails to result in appropriate morphorheological properties required for successful cell circulation. To address this issue, a method to culture MSCs in nonadherent 3D spheroids (mesenspheres) is adapted. The biological properties of mesensphere‐cultured MSCs remain identical to conventional 2D cultures. However, morphorheological analyses reveal a smaller size and lower stiffness of mesensphere‐derived MSCs compared to plastic‐adherent MSCs, measured using real‐time deformability cytometry and atomic force microscopy. These properties result in an increased ability to pass through microconstrictions in an ex vivo microcirculation assay. This ability is confirmed in vivo by comparison of cell accumulation in various organ capillary networks after intravenous injection of both types of MSCs in mouse. The findings generally identify cellular morphorheological properties as attractive targets for improving microcirculation and specifically suggest mesensphere culture as a promising approach for optimized MSC‐based therapies. John Wiley and Sons Inc. 2019-02-19 /pmc/articles/PMC6469243/ /pubmed/31016116 http://dx.doi.org/10.1002/advs.201802104 Text en © 2019 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full Papers
Tietze, Stefanie
Kräter, Martin
Jacobi, Angela
Taubenberger, Anna
Herbig, Maik
Wehner, Rebekka
Schmitz, Marc
Otto, Oliver
List, Catrin
Kaya, Berna
Wobus, Manja
Bornhäuser, Martin
Guck, Jochen
Spheroid Culture of Mesenchymal Stromal Cells Results in Morphorheological Properties Appropriate for Improved Microcirculation
title Spheroid Culture of Mesenchymal Stromal Cells Results in Morphorheological Properties Appropriate for Improved Microcirculation
title_full Spheroid Culture of Mesenchymal Stromal Cells Results in Morphorheological Properties Appropriate for Improved Microcirculation
title_fullStr Spheroid Culture of Mesenchymal Stromal Cells Results in Morphorheological Properties Appropriate for Improved Microcirculation
title_full_unstemmed Spheroid Culture of Mesenchymal Stromal Cells Results in Morphorheological Properties Appropriate for Improved Microcirculation
title_short Spheroid Culture of Mesenchymal Stromal Cells Results in Morphorheological Properties Appropriate for Improved Microcirculation
title_sort spheroid culture of mesenchymal stromal cells results in morphorheological properties appropriate for improved microcirculation
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469243/
https://www.ncbi.nlm.nih.gov/pubmed/31016116
http://dx.doi.org/10.1002/advs.201802104
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