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Enhancing the Therapeutic Potential of CCL2-Overexpressing Mesenchymal Stem Cells in Acute Stroke
- Source :
- International Journal of Molecular Sciences, Volume 21, Issue 20, International Journal of Molecular Sciences, Vol 21, Iss 7795, p 7795 (2020)
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
Abstract
- Although intravenous administration of mesenchymal stem cells (MSCs) is effective for experimental stroke, low engraftment and the limited functional capacity of transplanted cells are critical hurdles for clinical applications. C&ndash<br />C motif chemokine ligand 2 (CCL2) is associated with neurological repair after stroke and delivery of various cells into the brain via CCL2/CCR2 (CCL2 receptor) interaction. In this study, after CCL2-overexpressing human umbilical cord-derived MSCs (hUC-MSCs) were intravenously transplanted with mannitol in rats with middle cerebral arterial occlusion, we compared the differences between four different treatment groups: mannitol + CCL2-overexpressing hUC-MSCs (CCL2-MSC), mannitol + na&iuml<br />ve hUC-MSCs (M-MSC), mannitol only, and control. At four-weeks post-transplantation, the CCL2-MSC group showed significantly better functional recovery and smaller stroke volume relative to the other groups. Additionally, we observed upregulated levels of CCR2 in acute ischemic brain and the increase of migrated stem cells into these areas in the CCL2-MSC group relative to the M-MSC. Moreover, the CCL2-MSC group displayed increased angiogenesis and endogenous neurogenesis, decreased neuro-inflammation but with increased healing-process inflammatory cells relative to other groups. These findings indicated that CCL2-overexpressing hUC-MSCs showed better functional recovery relative to na&iuml<br />ve hUC-MSCs according to the increased migration of these cells into brain areas of higher CCR2 expression, thereby promoting subsequent endogenous brain repair.
- Subjects :
- Male
CCR2
Chemokine
Receptors, CCR2
Angiogenesis
Neurogenesis
Neovascularization, Physiologic
CCL2
Pharmacology
Mesenchymal Stem Cell Transplantation
Article
Catalysis
Brain Ischemia
Umbilical Cord
lcsh:Chemistry
Rats, Sprague-Dawley
Inorganic Chemistry
angiogenesis
Animals
Humans
Medicine
Physical and Theoretical Chemistry
lcsh:QH301-705.5
Molecular Biology
mesenchymal stem cell
Chemokine CCL2
Spectroscopy
biology
business.industry
Organic Chemistry
Mesenchymal stem cell
Brain
Infarction, Middle Cerebral Artery
Mesenchymal Stem Cells
General Medicine
stroke
Computer Science Applications
Disease Models, Animal
surgical procedures, operative
lcsh:Biology (General)
lcsh:QD1-999
biology.protein
Mannitol
Stem cell
business
medicine.drug
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....44056c26dc91f3f90bdda107dda12c69