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Updated: May 28, 2026
Isolation of Human BAMBIhighMFGE8high Umbilical Cord-Derived Mesenchymal Stromal Cells
Published on: January 10, 2025
Soluble intracellular adhesion molecule-1 secreted by human umbilical cord blood-derived mesenchymal stem cell
1Biomedical Research Institute, MEDIPOST Co. Ltd., Seoul 137-874, Republic of Korea.
Abstract:
Presently, co-culture of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) with BV2 microglia under amyloid-β42 (Aβ42) exposure induced a reduction of Aβ42 in the medium as well as an overexpression of the Aβ-degrading enzyme neprilysin (NEP) in microglia. Cytokine array examinations of co-cultured media revealed elevated release of soluble intracellular adhesion molecule-1 (sICAM-1) from hUCB-MSCs. Administration of human recombinant ICAM-1 in BV2 cells and wild-type mice brains induced NEP expression in time- and dose-dependent manners. In co-culturing with BV2 cells under Aβ42 exposure, knockdown of ICAM-1 expression on hUCB-MSCs by small interfering RNA (siRNA) abolished the induction of NEP in BV2 cells as well as reduction of added Aβ42 in the co-cultured media. By contrast, siRNA-mediated inhibition of the sICAM-1 receptor, lymphocyte function-associated antigen-1 (LFA-1), on BV2 cells reduced NEP expression by ICAM-1 exposure. When hUCB-MSCs were transplanted into the hippocampus of a 10-month-old transgenic mouse model of Alzheimer's disease for 10, 20, or 40 days, NEP expression was increased in the mice brains. Moreover, Aβ42 plaques in the hippocampus and other regions were decreased by active migration of hUCB-MSCs toward Aβ deposits. These data suggest that hUCB-MSC-derived sICAM-1 decreases Aβ plaques by inducing NEP expression in microglia through the sICAM-1/LFA-1 signaling pathway.
Insights
Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) reduce amyloid-beta (Aβ) plaques by enhancing microglial neprilysin (NEP) expression. This occurs via the soluble intercellular adhesion molecule-1 (sICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) pathway, offering a novel Alzheimer's disease therapeutic strategy.
Area of Science:
- Neuroscience
- Immunology
- Stem Cell Biology
Background:
- Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) plaque accumulation.
- Microglia play a crucial role in neuroinflammation and Aβ clearance.
- Mesenchymal stem cells (MSCs) show therapeutic potential in neurodegenerative diseases.
Purpose of the Study:
- To investigate the mechanism by which human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) reduce Aβ pathology.
- To elucidate the role of intercellular adhesion molecule-1 (ICAM-1) in hUCB-MSC-mediated microglial activation and Aβ degradation.
Main Methods:
- Co-culture of hUCB-MSCs with BV2 microglia under Aβ42 exposure.
- Cytokine array analysis to detect secreted factors.
- Small interfering RNA (siRNA) to knockdown ICAM-1 and its receptor, lymphocyte function-associated antigen-1 (LFA-1).
- Transplantation of hUCB-MSCs into an Alzheimer's disease mouse model.
Main Results:
- hUCB-MSCs reduced Aβ42 and increased microglial neprilysin (NEP) expression.
- hUCB-MSCs secreted soluble ICAM-1 (sICAM-1), which induced NEP expression in microglia.
- Knockdown of ICAM-1 on hUCB-MSCs or LFA-1 on microglia abolished Aβ reduction and NEP induction.
- Transplanted hUCB-MSCs migrated to Aβ deposits and reduced plaque load in AD mouse brains.
Conclusions:
- hUCB-MSC-derived sICAM-1 induces microglial NEP expression via the sICAM-1/LFA-1 pathway.
- This mechanism contributes to Aβ plaque reduction in vitro and in vivo.
- hUCB-MSCs represent a promising cell-based therapy for Alzheimer's disease by modulating microglial function.
