Peptoid-Cross-Linked Hydrogel Stiffness Modulates Human Mesenchymal Stromal Cell Immunoregulatory Potential in the Presence of Interferon-Gamma.

Castilla-Casadiego, David A; Morton, Logan D; Loh, Darren H; Pineda-Hernandez, Aldaly; Chavda, Ajay P; Garcia, Francis; Rosales, Adrianne M

Castilla-Casadiego, David A; Morton, Logan D; Loh, Darren H; Pineda-Hernandez, Aldaly; Chavda, Ajay P; Garcia, Francis; Rosales, Adrianne M.

Afiliación

Castilla-Casadiego DA; Mcketta Department of Chemical Engineering, University of Texas at Austin, Austin, TX, 78712, USA.
Morton LD; Mcketta Department of Chemical Engineering, University of Texas at Austin, Austin, TX, 78712, USA.
Loh DH; Mcketta Department of Chemical Engineering, University of Texas at Austin, Austin, TX, 78712, USA.
Pineda-Hernandez A; Mcketta Department of Chemical Engineering, University of Texas at Austin, Austin, TX, 78712, USA.
Chavda AP; Mcketta Department of Chemical Engineering, University of Texas at Austin, Austin, TX, 78712, USA.
Garcia F; Mcketta Department of Chemical Engineering, University of Texas at Austin, Austin, TX, 78712, USA.
Rosales AM; Mcketta Department of Chemical Engineering, University of Texas at Austin, Austin, TX, 78712, USA.

Macromol Biosci ; 24(7): e2400111, 2024 Jul.

Article en En | MEDLINE | ID: mdl-38567626

ABSTRACT

ABSTRACT

Human mesenchymal stromal cell (hMSC) manufacturing requires the production of large numbers of therapeutically potent cells. Licensing with soluble cytokines improves hMSC therapeutic potency by enhancing secretion of immunoactive factors but typically decreases proliferative ability. Soft hydrogels, however, have shown promise for boosting immunomodulatory potential, which may compensate for decreased proliferation. Here, hydrogels are cross-linked with peptoids of different secondary structures to generate substrates of various bulk stiffnesses but fixed network connectivity. Secretions of interleukin 6, monocyte chemoattractive protein-1, macrophage colony-stimulating factor, and vascular endothelial growth factor are shown to depend on hydrogel stiffness in the presence of interferon gamma (IFN-Î³) supplementation, with soft substrates further improving secretion. The immunological function of these secreted cytokines is then investigated via coculture of hMSCs seeded on hydrogels with primary peripheral blood mononuclear cells (PBMCs) in the presence and absence of IFN-Î³. Cocultures with hMSCs seeded on softer hydrogels show decreased PBMC proliferation with IFN-Î³. To probe possible signaling pathways, immunofluorescent studies probe the nuclear factor kappa B pathway and demonstrate that IFN-Î³ supplementation and softer hydrogel mechanics lead to higher activation of this pathway. Overall, these studies may allow for production of more efficacious therapeutic hMSCs in the presence of IFN-Î³.

Asunto(s)

Hidrogeles; Interferón gamma; Células Madre Mesenquimatosas; Humanos; Células Madre Mesenquimatosas/efectos de los fármacos; Células Madre Mesenquimatosas/metabolismo; Células Madre Mesenquimatosas/citología; Interferón gamma/metabolismo; Hidrogeles/química; Hidrogeles/farmacología; Leucocitos Mononucleares/efectos de los fármacos; Leucocitos Mononucleares/citología; Leucocitos Mononucleares/metabolismo; Proliferación Celular/efectos de los fármacos; Técnicas de Cocultivo; Citocinas/metabolismo

Palabras clave

human mesenchymal stromal cells; hydrogels; immunosuppression; secretome

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interferón gamma / Hidrogeles / Células Madre Mesenquimatosas Límite: Humans Idioma: En Revista: Macromol Biosci Asunto de la revista: BIOQUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania

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