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Effects of freeze-thawing and intravenous infusion on mesenchymal stromal cell gene expression.

Hoogduijn, Martin J; de Witte, Samantha; Luk, Franka; van den Hout-van Vroonhoven, Mirjam Cgn; Ignatowicz, Lech LU ; Catar, Rusan; Strini, Tanja; Korevaar, Sander S; van IJcken, Wilfred Fj and Betjes, Michiel Gh, et al. (2016) In Stem Cells and Development
Abstract
Mesenchymal stromal cells (MSC) are increasingly used as an investigative therapeutic product for immune disorders and degenerative disease. Typically, MSC are isolated from human tissue, expanded in culture and cryopreserved until usage. The safety and efficacy of MSC therapy will depend on the phenotypical and functional characteristics of MSC. The freeze-thawing procedure may change these characteristics. Furthermore, the cells encounter a microenvironment after administration that may impact their properties. It has been demonstrated that the majority of MSC localize to the lungs after intravenous infusion, making this the site to study the effects of the in vivo milieu on administered MSC. In the present study we investigated the... (More)
Mesenchymal stromal cells (MSC) are increasingly used as an investigative therapeutic product for immune disorders and degenerative disease. Typically, MSC are isolated from human tissue, expanded in culture and cryopreserved until usage. The safety and efficacy of MSC therapy will depend on the phenotypical and functional characteristics of MSC. The freeze-thawing procedure may change these characteristics. Furthermore, the cells encounter a microenvironment after administration that may impact their properties. It has been demonstrated that the majority of MSC localize to the lungs after intravenous infusion, making this the site to study the effects of the in vivo milieu on administered MSC. In the present study we investigated the effect of freeze-thawing and the mouse lung microenvironment on human adipose tissue-derived MSC. There were effects of freeze-thawing on the whole genome expression profile of MSC, although the effects did not exceed inter-donor differences. There were no major changes in the expression of hemostatic regulators on transcriptional level, but significantly increased expression of procoagulant tissue factor on the surface of thawed adipose MSC, correlating with increased procoagulant activity of thawed cells. Exposure for 2h to the lung microenvironment had a major effect on MSC gene expression and affected several immunological pathways. This indicates that MSC undergo functional changes shortly after infusion and this may influence the efficacy of MSC to modulate inflammatory responses. The results of this study demonstrate that MSC rapidly alter in response to the local milieu and that disease specific conditions may shape MSC after administration. (Less)
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Stem Cells and Development
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Mary Ann Liebert, Inc.
external identifiers
  • pmid:26914168
  • wos:000373939700002
  • scopus:84964853877
ISSN
1557-8534
DOI
10.1089/scd.2015.0329
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English
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yes
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ddf799a0-0d4a-447c-bc69-6890d599f314 (old id 8821686)
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http://www.ncbi.nlm.nih.gov/pubmed/26914168?dopt=Abstract
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2016-03-02 09:45:50
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@article{ddf799a0-0d4a-447c-bc69-6890d599f314,
  abstract     = {Mesenchymal stromal cells (MSC) are increasingly used as an investigative therapeutic product for immune disorders and degenerative disease. Typically, MSC are isolated from human tissue, expanded in culture and cryopreserved until usage. The safety and efficacy of MSC therapy will depend on the phenotypical and functional characteristics of MSC. The freeze-thawing procedure may change these characteristics. Furthermore, the cells encounter a microenvironment after administration that may impact their properties. It has been demonstrated that the majority of MSC localize to the lungs after intravenous infusion, making this the site to study the effects of the in vivo milieu on administered MSC. In the present study we investigated the effect of freeze-thawing and the mouse lung microenvironment on human adipose tissue-derived MSC. There were effects of freeze-thawing on the whole genome expression profile of MSC, although the effects did not exceed inter-donor differences. There were no major changes in the expression of hemostatic regulators on transcriptional level, but significantly increased expression of procoagulant tissue factor on the surface of thawed adipose MSC, correlating with increased procoagulant activity of thawed cells. Exposure for 2h to the lung microenvironment had a major effect on MSC gene expression and affected several immunological pathways. This indicates that MSC undergo functional changes shortly after infusion and this may influence the efficacy of MSC to modulate inflammatory responses. The results of this study demonstrate that MSC rapidly alter in response to the local milieu and that disease specific conditions may shape MSC after administration.},
  author       = {Hoogduijn, Martin J and de Witte, Samantha and Luk, Franka and van den Hout-van Vroonhoven, Mirjam Cgn and Ignatowicz, Lech and Catar, Rusan and Strini, Tanja and Korevaar, Sander S and van IJcken, Wilfred Fj and Betjes, Michiel Gh and Franquesa, Marcella and Moll, Guido and Baan, Carla C},
  issn         = {1557-8534},
  language     = {eng},
  month        = {02},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {Stem Cells and Development},
  title        = {Effects of freeze-thawing and intravenous infusion on mesenchymal stromal cell gene expression.},
  url          = {http://dx.doi.org/10.1089/scd.2015.0329},
  year         = {2016},
}