ArticleFrontiers in immunology2022
Licensing microgels prolong the immunomodulatory phenotype of mesenchymal stromal cells.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- Article
- From mitochondria to immune networks: new mesenchymal stem cell strategies to treat periodontitis.Stem cell research & therapy · 2025Review
- Immunomodulatory potential of cytokine-licensed human bone marrow-derived mesenchymal stromal cells correlates with potency marker expression profile.Stem cells (Dayton, Ohio) · 2024Article
- Granular Hydrogels for Harnessing the Immune Response.Advanced healthcare materials · 2024Review
- Substrate curvature influences cytoskeletal rearrangement and modulates macrophage phenotype.Frontiers in immunology · 2024Article
- Advancements in engineered mesenchymal stem cell exosomes for chronic lung disease treatment.Journal of translational medicine · 2023Review
- Biomechanical Stimulation of Muscle Constructs Influences Phenotype of Bone Constructs by Modulating Myokine Secretion.JBMR plus · 2023Article
- Injectable nanoporous microgels generate vascularized constructs and support bone regeneration in critical-sized defects.Scientific reports · 2022Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Mesenchymal stromal cells (MSC) are sensors of inflammation, and they exert immunomodulatory properties through the secretion of cytokines and exosomes and direct cell-cell interactions. MSC are routinely used in clinical trials and effectively resolve inflammatory conditions. Nevertheless, inconsistent clinical outcomes necessitate the need for more robust therapeutic phenotypes. The immunomodulatory properties of MSC can be enhanced and protracted by priming (aka licensing) them with IFNγ and TNFα. Yet these enhanced properties rapidly diminish, and prolonged stimulation could tolerize their response. Hence a balanced approach is needed to enhance the therapeutic potential of the MSC for consistent clinical performance. Here, we investigated the concentration-dependent effects of IFNγ and TNFα and developed gelatin-based microgels to sustain a licensed MSC phenotype. We show that IFNγ treatment is more beneficial than TNFα in promoting an immunomodulatory MSC phenotype. We also show that the microgels possess integrin-binding sites to support adipose tissue-derived MSC (AD-MSC) attachment and a net positive charge to sequester the licensing cytokines electrostatically. Microgels are enzymatically degradable, and the rate is dependent on the enzyme concentration and matrix density. Our studies show that one milligram of microgels by dry mass can sequester up to 641 ± 81 ng of IFNγ. Upon enzymatic degradation, microgels exhibited a sustained release of IFNγ that linearly correlated with their degradation rate. The AD-MSC cultured on the IFNγ sequestered microgels displayed efficient licensing potential comparable to or exceeding the effects of bolus IFNγ treatment. When cultured with proinflammatory M1-like macrophages, the AD-MSC-seeded on licensing microgel showed an enhanced immunomodulatory potential compared to untreated AD-MSC and AD-MSC treated with bolus IFNγ treatment. Specifically, the AD-MSC seeded on licensing microgels significantly upregulated
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