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UC-MSCs based on biomimetic microniche exert excellent regulatory effects on acute brain inflammation through
Bichun Zhao1, Chao Wang1, Manqiang Sun1
1Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
Abstract:
Neuroinflammation triggered by activated microglia leads to neuronal damage and, to a certain extent, neurodegeneration. Human umbilical cord mesenchymal stem cells (UC-MSCs) have good immunomodulatory and neuroprotective effects as well as therapeutic potential for neuroinflammation-related diseases. However, the complex microenvironment created by neuroinflammation poses a challenge to transplanted UC-MSCs. The emerging biomimetic microniche (BN)-based culture technology provides new opportunities to optimize the preparation of UC-MSCs; but the fundamental changes in the characteristics of UC-MSCs based on BN remain unclear, and more reliable preclinical data are needed to support their ability to regulate inflammation. Here, we systematically studied the cellular properties and inflammation regulatory capacity of UC-MSCs in conventional static planar culture (SP-UCMSCs) and suspension culture based on BN (BN-UCMSCs). In vitro, compared with SP-UCMSCs, BN-UCMSCs not only maintained the fundamental characteristics of MSCs, but also significantly enhanced cell proliferation, adhesion, and migration capabilities, etc; notably, the paracrine function and anti-inflammatory capacity of BN-UCMSCs were also enhanced. We further established a murine model of acute brain inflammation and demonstrated that the expression level of pro-inflammatory cytokines in hippocampal and cortical tissues of the BN-UCMSCs group was significantly decreased compared with that in the SP-UCMSCs group. Subsequent transcriptomic analysis of hippocampal and cortical tissues revealed that BN-UCMSCs had the advantage of significantly reducing the expression of pro-inflammatory cytokines through the TLR4-Myd88-NF-κB axis, which was further validated at the gene and protein levels. Taken together, these data strongly indicated that BN-UCMSCs exerts excellent regulatory effects on acute brain inflammation through advantageous properties.
Insights
Biomimetic microniche (BN)-cultured human umbilical cord mesenchymal stem cells (UC-MSCs) show enhanced anti-inflammatory effects in brain inflammation models. BN-UC-MSCs improve cell properties and reduce pro-inflammatory cytokines via the TLR4-Myd88-NF-κB pathway.
Area of Science:
- Stem cell biology
- Neuroinflammation research
- Biomaterials science
Background:
- Neuroinflammation, driven by microglia, causes neuronal damage and neurodegeneration.
- Human umbilical cord mesenchymal stem cells (UC-MSCs) offer immunomodulatory and neuroprotective potential for neuroinflammatory diseases.
- The neuroinflammatory microenvironment challenges transplanted UC-MSC efficacy, necessitating optimized preparation methods.
Purpose of the Study:
- To systematically investigate the cellular properties and inflammation regulatory capacity of UC-MSCs cultured in a biomimetic microniche (BN) suspension compared to conventional static planar culture (SP).
- To evaluate the therapeutic potential of BN-cultured UC-MSCs in a murine model of acute brain inflammation.
Main Methods:
- Comparative in vitro analysis of UC-MSCs cultured using static planar (SP-UC-MSCs) and biomimetic microniche (BN-UC-MSCs) suspension methods.
- Assessment of cell proliferation, adhesion, migration, paracrine function, and anti-inflammatory capacity.
- Establishment of a murine acute brain inflammation model to evaluate the in vivo efficacy of SP-UC-MSCs versus BN-UC-MSCs.
- Transcriptomic, gene, and protein level analysis of inflammatory pathways (TLR4-Myd88-NF-κB axis) in brain tissues.
Main Results:
- BN-UC-MSCs exhibited enhanced proliferation, adhesion, and migration compared to SP-UC-MSCs, while retaining fundamental MSC characteristics.
- BN-UC-MSCs demonstrated significantly improved paracrine function and anti-inflammatory capacity in vitro.
- In vivo, BN-UC-MSCs significantly reduced pro-inflammatory cytokine expression in hippocampal and cortical tissues of mice with acute brain inflammation.
- Transcriptomic analysis revealed that BN-UC-MSCs suppress pro-inflammatory cytokine expression via the TLR4-Myd88-NF-κB pathway.
Conclusions:
- Biomimetic microniche culture enhances the functional properties and therapeutic potential of human umbilical cord mesenchymal stem cells.
- BN-cultured UC-MSCs demonstrate superior efficacy in regulating acute brain inflammation, offering a promising strategy for neuroinflammation-related diseases.
- The TLR4-Myd88-NF-κB pathway is a key mechanism through which BN-UC-MSCs exert their anti-inflammatory effects.
