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Integrin α10β1-selected mesenchymal stem cells reduced hypercoagulopathy in a porcine model of acute respiratory distress syndrome

Edström, Dag LU ; Niroomand, Anna LU ; Stenlo, Martin LU ; Uvebrant, Kristina ; Bölükbas, Deniz A LU ; Hirdman, Gabriel LU ; Broberg, Ellen LU ; Lim, Hooi Ching LU ; Hyllén, Snejana LU and Lundgren-Åkerlund, Evy LU , et al. (2023) In Respiratory Research 24(1).
Abstract

Mesenchymal stem cells (MSCs) have been studied for their potential benefits in treating acute respiratory distress syndrome (ARDS) and have reported mild effects when trialed within human clinical trials. MSCs have been investigated in preclinical models with efficacy when administered at the time of lung injury. Human integrin α10β1-selected adipose tissue-derived MSCs (integrin α10β1-MSCs) have shown immunomodulatory and regenerative effects in various disease models. We hypothesized that integrin α10β1 selected-MSCs can be used to treat a sepsis-induced ARDS in a porcine model when administering cells after established injury rather than simultaneously. This was hypothesized to reflect a clinical picture of treatment with MSCs in... (More)

Mesenchymal stem cells (MSCs) have been studied for their potential benefits in treating acute respiratory distress syndrome (ARDS) and have reported mild effects when trialed within human clinical trials. MSCs have been investigated in preclinical models with efficacy when administered at the time of lung injury. Human integrin α10β1-selected adipose tissue-derived MSCs (integrin α10β1-MSCs) have shown immunomodulatory and regenerative effects in various disease models. We hypothesized that integrin α10β1 selected-MSCs can be used to treat a sepsis-induced ARDS in a porcine model when administering cells after established injury rather than simultaneously. This was hypothesized to reflect a clinical picture of treatment with MSCs in human ARDS. 12 pigs were randomized to the treated or placebo-controlled group prior to the induction of mild to moderate ARDS via lipopolysaccharide administration. The treated group received 5 × 10
6 cells/kg integrin α10β1-selected MSCs and both groups were followed for 12 h. ARDS was confirmed with blood gases and retrospectively with histological changes. After intervention, the treated group showed decreased need for inotropic support, fewer signs of histopathological lung injury including less alveolar wall thickening and reduction of the hypercoagulative disease state. The MSC treatment was not associated with adverse events over the monitoring period. This provides new opportunities to investigate integrin α10β1-selected MSCs as a treatment for a disease which does not yet have any definitive therapeutic options.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Integrins, Lung Injury, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells, Respiratory Distress Syndrome/diagnosis, Retrospective Studies, Swine
in
Respiratory Research
volume
24
issue
1
article number
145
pages
17 pages
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85160797090
  • pmid:37259141
ISSN
1465-9921
DOI
10.1186/s12931-023-02459-6
language
English
LU publication?
yes
additional info
© 2023. The Author(s).
id
64848b4c-2525-4ce6-9a6b-d815c74b3d10
date added to LUP
2023-06-05 19:07:07
date last changed
2024-06-15 03:45:40
@article{64848b4c-2525-4ce6-9a6b-d815c74b3d10,
  abstract     = {{<p>Mesenchymal stem cells (MSCs) have been studied for their potential benefits in treating acute respiratory distress syndrome (ARDS) and have reported mild effects when trialed within human clinical trials. MSCs have been investigated in preclinical models with efficacy when administered at the time of lung injury. Human integrin α10β1-selected adipose tissue-derived MSCs (integrin α10β1-MSCs) have shown immunomodulatory and regenerative effects in various disease models. We hypothesized that integrin α10β1 selected-MSCs can be used to treat a sepsis-induced ARDS in a porcine model when administering cells after established injury rather than simultaneously. This was hypothesized to reflect a clinical picture of treatment with MSCs in human ARDS. 12 pigs were randomized to the treated or placebo-controlled group prior to the induction of mild to moderate ARDS via lipopolysaccharide administration. The treated group received 5 × 10 <br>
 6 cells/kg integrin α10β1-selected MSCs and both groups were followed for 12 h. ARDS was confirmed with blood gases and retrospectively with histological changes. After intervention, the treated group showed decreased need for inotropic support, fewer signs of histopathological lung injury including less alveolar wall thickening and reduction of the hypercoagulative disease state. The MSC treatment was not associated with adverse events over the monitoring period. This provides new opportunities to investigate integrin α10β1-selected MSCs as a treatment for a disease which does not yet have any definitive therapeutic options.<br>
 </p>}},
  author       = {{Edström, Dag and Niroomand, Anna and Stenlo, Martin and Uvebrant, Kristina and Bölükbas, Deniz A and Hirdman, Gabriel and Broberg, Ellen and Lim, Hooi Ching and Hyllén, Snejana and Lundgren-Åkerlund, Evy and Pierre, Leif and Olm, Franziska and Lindstedt, Sandra}},
  issn         = {{1465-9921}},
  keywords     = {{Animals; Integrins; Lung Injury; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Respiratory Distress Syndrome/diagnosis; Retrospective Studies; Swine}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Respiratory Research}},
  title        = {{Integrin α10β1-selected mesenchymal stem cells reduced hypercoagulopathy in a porcine model of acute respiratory distress syndrome}},
  url          = {{http://dx.doi.org/10.1186/s12931-023-02459-6}},
  doi          = {{10.1186/s12931-023-02459-6}},
  volume       = {{24}},
  year         = {{2023}},
}