Cargando…
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783411608819597312 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6469243 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT tietzestefanie spheroidcultureofmesenchymalstromalcellsresultsinmorphorheologicalpropertiesappropriateforimprovedmicrocirculation AT kratermartin spheroidcultureofmesenchymalstromalcellsresultsinmorphorheologicalpropertiesappropriateforimprovedmicrocirculation AT jacobiangela spheroidcultureofmesenchymalstromalcellsresultsinmorphorheologicalpropertiesappropriateforimprovedmicrocirculation AT taubenbergeranna spheroidcultureofmesenchymalstromalcellsresultsinmorphorheologicalpropertiesappropriateforimprovedmicrocirculation AT herbigmaik spheroidcultureofmesenchymalstromalcellsresultsinmorphorheologicalpropertiesappropriateforimprovedmicrocirculation AT wehnerrebekka spheroidcultureofmesenchymalstromalcellsresultsinmorphorheologicalpropertiesappropriateforimprovedmicrocirculation AT schmitzmarc spheroidcultureofmesenchymalstromalcellsresultsinmorphorheologicalpropertiesappropriateforimprovedmicrocirculation AT ottooliver spheroidcultureofmesenchymalstromalcellsresultsinmorphorheologicalpropertiesappropriateforimprovedmicrocirculation AT listcatrin spheroidcultureofmesenchymalstromalcellsresultsinmorphorheologicalpropertiesappropriateforimprovedmicrocirculation AT kayaberna spheroidcultureofmesenchymalstromalcellsresultsinmorphorheologicalpropertiesappropriateforimprovedmicrocirculation AT wobusmanja spheroidcultureofmesenchymalstromalcellsresultsinmorphorheologicalpropertiesappropriateforimprovedmicrocirculation AT bornhausermartin spheroidcultureofmesenchymalstromalcellsresultsinmorphorheologicalpropertiesappropriateforimprovedmicrocirculation AT guckjochen spheroidcultureofmesenchymalstromalcellsresultsinmorphorheologicalpropertiesappropriateforimprovedmicrocirculation |