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Chirality Controls Mesenchymal Stem Cell Lineage Diversification through Mechanoresponses
Yan Wei1, Shengjie Jiang1, Mengting Si1
1Beijing Laboratory of Biomedical Materials, Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China.
Advanced Materials (Deerfield Beach, Fla.)
|March 7, 2019
Summary
Chirality in a 3D extracellular matrix guides stem cell differentiation into bone and fat cells. This discovery offers new strategies for tissue development and regenerative medicine.
Area of Science:
- Biomaterials Science
- Stem Cell Biology
- Mechanobiology
Background:
- Multipotent stem cell heterogenesis drives tissue development, but mechanisms of fate specification remain unclear.
- Chirality influences stem cell development and cell morphology, yet its role in heterogeneous cell fate determination is not well understood.
Purpose of the Study:
- To investigate how the chirality of a 3D extracellular matrix (ECM) influences mesenchymal stem cell differentiation.
- To elucidate the molecular mechanisms underlying chirality-dependent stem cell fate specification.
Main Methods:
- Fabrication of a 3D extracellular matrix (ECM) with defined chirality.
- Molecular analysis of stem cell differentiation pathways.
- Theoretical modeling of cell-matrix interactions.
Main Results:
- Chirality of the 3D ECM directed mesenchymal stem cells towards osteogenic and adipogenic lineages.
- Left-handed ECM chirality promoted clustering of the mechanosensor Integrin alpha-5 (Itgα5), while right-handed chirality reduced it.
- Differential adhesion patterns activated specific mechanotransduction pathways, including FAK/ERK1/2 and YAP/RUNX2 signaling, directing heterogeneous differentiation.
Conclusions:
- Stem cell lineage specification is dependent on the chirality of the extracellular matrix.
- Chirality provides primary heterogeneity for stem cell differentiation.
- Findings offer potential strategies for organism biogenesis and regenerative therapies.
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