International Journal of Stem Cells : eISSN 2005-5447

Table. 2.

Table. 2.

Enhancement of MSC immunomodulation through various cell culture methods for each type of biomimetic ECM

Type of ECM Method MSC source Immunomodulation References
Spheroid Hanging drop Human bone marrow Increased secretion of TSG-6, STC-1, LIF (35)
Hanging drop Human bone marrow High anti-inflammatory effect through TSG-6, TRAIL, IL-24 expression and PGE2 secretion (37)
Hanging drop Human umbilical cord Increased expression of IL-6, MCP-1, LIF, G-CSF, SDF-1α, and decreased levels of TGF-β1, TGF-β2 in 3D culture conditions compared to 2D culture (36)
Hydrogel Human bone marrow Increased expression of IDO1, GAL9, PTGS2, IL1RN, HGF, IL-10 in hydrogel spheroids compared to 2D (38)
Floating Human bone marrow Increased HO-1, PTGES, COX-2 gene expression and PGE2 secretion (40)
Spinner flask culture Human umbilical cord 3D MSC-derived exosomes reduced the systemic levels of pro-inflammatory cytokines (IL-6, TNF-α) in vivo at late stage of wound healing; increased secretion of IL-10, TGF-β, TNF-α or upregulated IL-1α and VEGF-α in vitro compared to 2D MSC-derived exosome (42, 43)
Scaffold Decellularized liver scaffold Human umbilical cord Increased PGE2 secretion by the 3D group and decreased IFN-γ (44)
Silk fibroin nanofiber Human bone marrow MSC on silk fibroin scaffolds elevated IDO1, COX-2, PGE2 expression and reduced mortality in sepsis-induced animal models (47)
PCL/SF fibrous scaffold Human bone marrow M2 macrophage polarization and inhibited expression of cytokines (IL-1β, CXCL11, IL-10, IL1R2, TGF-β1) (45)
PLLA fibrous scaffold (PLLA fibrous scaffold, aligned fiber) Human adipose tissue Aligned fiber MSC enhanced the expression and secretion levels of TSG-6, COX-2 compared to random fiber MSCs, probably due to increased activation of YAP/TAZ signaling (48)
PCL fibrous scaffold (PCL fibrous random, mesh, aligned like fiber scaffold) Rat adipose tissue Increased gene expression and cytokine secretion of COX-2, TSG-6, iNOS, PGE2, TGF-β in MSCs from random, aligned, and mesh-patterned scaffolds compared to microplates (46)
Porous scaffold (collagen, chitosan, PLGA substrate) Human umbilical cord Increased levels of IL1A, IL1B, IL1RN, IL6ST, VEGF, HGF genes and PTGS2, IL1RN, IL-1β proteins (50)
Porous scaffold (polystyrene) Human bone marrow MSCs in scaffold decreased IL-6, MCP-1 secretion and increased PGE2, TSG-6 levels (49)
Rigidity Stiffness Mouse MSC Increased MSC protein production of inflammatory modulators (IDO1 and PGE2) when hydrogel stiffness increased from 3 to 18 kPa (51)
Stiffness Human bone marrow TNF-α-primed MSCs in soft ECM (∼2 kPa) mimicking bone marrow maximized the ability of MSCs to produce paracrine factors that induced chemotaxis upon inflammatory stimulation (52)
Elasticity Human bone marrow More VEGF secreted by MSC in stiffer gels, while PGE2 secretion was highest in more compliant gels (53)
Functionalization of substrate surface Thermoplastic polyurethane plates with grid-like cavities or no structure Human bone marrow Enhanced secretion levels of immune modulators (PGE2, IL1RA) by MSCs on grid-like structure (44)
RGD peptide Human bone marrow T/DOP-IL-4/CG-RGD surface induced the conversion of macrophages to the M2 and increased the expression of IL-10 compared to T/DOP/CG (45)

MSC: mesenchymal stromal cell, ECM: extracellular matrix, TSG-6: tumor necrosis factor-alpha (TNF-α)-stimulated gene protein-6, STC-1: stanniocalcin-1, LIF: leukemia inhibitory factor, TRAIL: tumor necrosis factor-related apoptosis-inducing ligand, IL-24: interleukin-24, PGE2: prostaglandin E2, IL-6: interleukin-6, MCP-1: monocyte chemoattractant protein-1, G-CSF: granulocyte-colony stimulating factor, SDF-1α: stromal cell-derived factor 1 alpha, TGF-β1: transforming growth factor-beta 1, TGF-β2: transforming growth factor-beta 2, 3D: three-dimensional, 2D: two-dimensional, IDO1: indoleamine 2,3-dioxygenase, GAL9: galectin-9, PTGS2: prostaglandin-endoperoxide synthase 2/cyclooxygenase 2, IL1RN: interleukin-1 receptor antagonist, HGF: hepatocyte growth factor, IL-10: interleukin-10, HO-1: heme oxygenase-1, PTGES: prostaglandin E synthase, COX-2: cyclooxygenase-2, TNF-α: tumor necrosis factor-alpha, IL-10: interleukin-10, IL-1α: interleukin-1 alpha, VEGF-α: vascular endothelial growth factor-alpha, TGF-β: transforming growth factor-beta, IFN-γ: interferon-gamma, PCL: poly (ε-caprolactone), SF: silk fibroin, IL-1β: interleukin-1 beta, CXCL11: C-X-C motif chemokine ligand 11, IL1R2: interleukin-1 receptor type 2, PLLA: poly (L-lactic acid), YAP: Yes-associated protein, TAZ: transcriptional coactivator with a PDZ-binding domain, iNOS: inducible nitric oxide synthase, PLGA: poly (lactic-co-glycolic acid), IL6ST: interleukin-6 cytokine family signal transducer, IL1RA: interleukin-1 receptor antagonist (encoded by the IL1RN gene), RGD: arginine-glycine-aspartate, T: titanium, DOP: poly(dopamine), IL-4: interleukin-4, CG: carboxymethyl chitosan hydrogel layer, IL1A: interleukin 1 alpha, IL1B: interleukin 1 beta, VEGF: vascular endothelial growth factor.

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