Back to Search
Start Over
CXCR5-Overexpressing Mesenchymal Stromal Cells Exhibit Enhanced Homing and Can Decrease Contact Hypersensitivity.
- Source :
-
Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2017 Jun 07; Vol. 25 (6), pp. 1434-1447. Date of Electronic Publication: 2017 Apr 26. - Publication Year :
- 2017
-
Abstract
- Mesenchymal stromal cells (MSCs) can modulate inflammation and contribute to tissue regeneration and, thus, have emerged as a promising option for cell-based therapy. However, the ability of MSCs to migrate to injured tissues still needs to be improved. In this study, we investigated whether genetically engineered MSCs could exhibit increased migratory properties and improved therapeutic efficacy. Using a mouse model of contact hypersensitivity (CHS), chemokine gene expression screening revealed that CXCL13 changed most significantly in injured tissue. Unfortunately, MSCs hardly express the corresponding receptor, CXCR5. Thus, CXCR5-overexpressing MSCs (MSC <superscript>CXCR5</superscript> ) were generated that retained their abilities of proliferation, differentiation, and immunomodulation. Furthermore, MSC <superscript>CXCR5</superscript> showed significantly increased migrating ability toward CXCL13. Importantly, systemic infusion of MSC <superscript>CXCR5</superscript> dramatically suppressed CHS in mice, as evidenced by decreased levels of inflammatory cell infiltration and pro-inflammatory cytokine production. Numerous MSC <superscript>CXCR5</superscript> migrated into inflamed ears, localized with T cells, inhibited T cell proliferation, promoted T cell apoptosis, and suppressed the production of T cell-derived pro-inflammatory factors. Collectively, these findings demonstrate that CXCR5 overexpression increases the ability of MSCs to respond to migratory stimuli and highly intensifies their immunomodulatory effects in vivo. This strategy for enhancing targeted stem/progenitor cell homing may improve the efficacy of MSC-based therapies.<br /> (Copyright © 2017. Published by Elsevier Inc.)
- Subjects :
- Animals
Biomarkers
Chemokine CXCL13 genetics
Chemokine CXCL13 metabolism
Cytokines metabolism
Dermatitis, Contact metabolism
Disease Models, Animal
Gene Expression Regulation
Humans
Immunomodulation
Inflammation Mediators metabolism
Male
Mice
Receptors, Chemokine genetics
Receptors, Chemokine metabolism
T-Lymphocyte Subsets immunology
T-Lymphocyte Subsets metabolism
Cell Movement genetics
Dermatitis, Contact genetics
Dermatitis, Contact immunology
Gene Expression
Mesenchymal Stem Cells metabolism
Receptors, CXCR5 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1525-0024
- Volume :
- 25
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Molecular therapy : the journal of the American Society of Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 28454789
- Full Text :
- https://doi.org/10.1016/j.ymthe.2017.04.004