Endogenous stem cell mobilization and localized immunosuppression synergistically ameliorate DSS-induced Colitis in mice.
Animals
Colitis
/ chemically induced
Mice
Benzylamines
Male
Cyclams
/ pharmacology
Dextran Sulfate
Mice, Inbred C57BL
Tacrolimus
/ pharmacology
Hematopoietic Stem Cell Mobilization
/ methods
Heterocyclic Compounds
/ pharmacology
Hematopoietic Stem Cells
/ drug effects
Disease Models, Animal
Immunosuppression Therapy
Immunosuppressive Agents
/ pharmacology
Microspheres
Reactive Oxygen Species
/ metabolism
AMD-3100
Combination therapy
FK506
Hematopoietic stem cells
Stem cell mobilizing effect
Thioketal microspheres
Journal
Stem cell research & therapy
ISSN: 1757-6512
Titre abrégé: Stem Cell Res Ther
Pays: England
ID NLM: 101527581
Informations de publication
Date de publication:
13 Jun 2024
13 Jun 2024
Historique:
received:
05
01
2024
accepted:
28
05
2024
medline:
14
6
2024
pubmed:
14
6
2024
entrez:
13
6
2024
Statut:
epublish
Résumé
Stem cell therapy is a promising alternative for inflammatory diseases and tissue injury treatment. Exogenous delivery of mesenchymal stem cells is associated with instant blood-mediated inflammatory reactions, mechanical stress during administration, and replicative senescence or change in phenotype during long-term culture in vitro. In this study, we aimed to mobilize endogenous hematopoietic stem cells (HSCs) using AMD-3100 and provide local immune suppression using FK506, an immunosuppressive drug, for the treatment of inflammatory bowel diseases. Reactive oxygen species (ROS)-responsive FK506-loaded thioketal microspheres were prepared by emulsification solvent-evaporation method. Thioketal vehicle based FK506 microspheres and AMD3100 were co-administered into male C57BL6/J mice with dextran sulfate sodium (DSS) induced colitis. The effect of FK506-loaded thioketal microspheres in colitis mice were evaluated using disease severity index, myeloperoxidase activity, histology, flow cytometry, and gene expression by qRT-PCR. The delivery of AMD-3100 enhanced mobilization of HSCs from the bone marrow into the inflamed colon of mice. Furthermore, targeted oral delivery of FK506 in an inflamed colon inhibited the immune activation in the colon. In the DSS-induced colitis mouse model, the combination of AMD-3100 and FK506-loaded thioketal microspheres ameliorated the disease, decreased immune cell infiltration and activation, and improved body weight, colon length, and epithelial healing process. This study shows that the significant increase in the percentage of mobilized hematopoietic stem cells in the combination therapy of AMD and oral FK506 microspheres may contribute to a synergistic therapeutic effect. Thus, low-dose local delivery of FK506 combined with AMD3100 could be a promising alternative treatment for inflammatory bowel diseases.
Sections du résumé
BACKGROUND
BACKGROUND
Stem cell therapy is a promising alternative for inflammatory diseases and tissue injury treatment. Exogenous delivery of mesenchymal stem cells is associated with instant blood-mediated inflammatory reactions, mechanical stress during administration, and replicative senescence or change in phenotype during long-term culture in vitro. In this study, we aimed to mobilize endogenous hematopoietic stem cells (HSCs) using AMD-3100 and provide local immune suppression using FK506, an immunosuppressive drug, for the treatment of inflammatory bowel diseases.
METHODS
METHODS
Reactive oxygen species (ROS)-responsive FK506-loaded thioketal microspheres were prepared by emulsification solvent-evaporation method. Thioketal vehicle based FK506 microspheres and AMD3100 were co-administered into male C57BL6/J mice with dextran sulfate sodium (DSS) induced colitis. The effect of FK506-loaded thioketal microspheres in colitis mice were evaluated using disease severity index, myeloperoxidase activity, histology, flow cytometry, and gene expression by qRT-PCR.
RESULTS
RESULTS
The delivery of AMD-3100 enhanced mobilization of HSCs from the bone marrow into the inflamed colon of mice. Furthermore, targeted oral delivery of FK506 in an inflamed colon inhibited the immune activation in the colon. In the DSS-induced colitis mouse model, the combination of AMD-3100 and FK506-loaded thioketal microspheres ameliorated the disease, decreased immune cell infiltration and activation, and improved body weight, colon length, and epithelial healing process.
CONCLUSION
CONCLUSIONS
This study shows that the significant increase in the percentage of mobilized hematopoietic stem cells in the combination therapy of AMD and oral FK506 microspheres may contribute to a synergistic therapeutic effect. Thus, low-dose local delivery of FK506 combined with AMD3100 could be a promising alternative treatment for inflammatory bowel diseases.
Identifiants
pubmed: 38872206
doi: 10.1186/s13287-024-03777-2
pii: 10.1186/s13287-024-03777-2
doi:
Substances chimiques
Benzylamines
0
Cyclams
0
Dextran Sulfate
9042-14-2
plerixafor
S915P5499N
Tacrolimus
WM0HAQ4WNM
Heterocyclic Compounds
0
Immunosuppressive Agents
0
Reactive Oxygen Species
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
167Subventions
Organisme : Ministry of Science and ICT, South Korea
ID : 2021K1A3A1A20002609
Organisme : Ministry of Science and ICT, South Korea
ID : RS-2023-00272815
Organisme : Ministry of Science and ICT, South Korea
ID : 22A0205L1
Organisme : Ministry of Science and ICT, South Korea
ID : 23A0205L1
Organisme : Korean Government (MIST)
ID : 2022M3A9G8017220
Informations de copyright
© 2024. The Author(s).
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