Improving the immunomodulatory function of mesenchymal stem cells by defined chemical approach

Cheng, Jintao; Feng, Yuan; Xing, Feng; Wu, Dianming; Li, Xu; Rao, Zhihua; Li, Cuiping; Lin, Nan; Jia, Changchang; Zhang, Qi

doi:10.3389/fimmu.2022.1005426

Cited by 3 publications

(3 citation statements)

References 59 publications

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“…MSCs inhibit T cell functions by producing immunosuppressive factors and by direct cell–cell contacts. The soluble mediators produced by MSCs are TGF-β, prostaglandin E 2 (PGE 2 ), indoleamine 2,3-dioxygenase (IDO), IL-10, and nitric oxide, all of which inhibit the activation of inflammatory leukocytes 11 . MSCs also increase the proliferation and functions of Tregs.…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal stem cells enhance CCL8 expression by podocytes in lupus-prone MRL.Faslpr mice

Kim

Lee

Kim

et al. 2023

Sci Rep

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Nephritis is common in systemic lupus erythematosus patients and is associated with hyper-activation of immune and renal cells. Although mesenchymal stem cells (MSCs) ameliorate nephritis by inhibiting T and B cells, whether MSCs directly affect renal cells is unclear. To address this issue, we examined the direct effect of MSCs on renal cells with a focus on chemokines. We found that expression of CCL2, CCL3, CCL4, CCL5, CCL8, CCL19, and CXCL10 increased 1.6–5.6-fold in the kidney of lupus-prone MRL.Faslpr mice with advancing age from 9 to 16 weeks. Although MSCs inhibited the increase in the expression of most chemokines by 52–95%, they further increased CCL8 expression by 290%. Using renal cells, we next investigated how MSCs enhanced CCL8 expression. CCL8 was expressed by podocytes, but not by tubular cells. MSCs enhanced CCL8 expression by podocytes in a contact-dependent manner, which was proved by transwell assay and blocking with anti-VCAM-1 antibody. Finally, we showed that CCL8 itself activated MSCs to produce more immunosuppressive factors (IL-10, IDO, TGF-β1, and iNOS) and to inhibit more strongly IFN-γ production by T cells. Taken together, our data demonstrate that MSCs activate podocytes to produce CCL8 in a contact-dependent manner and conversely, podocyte-derived CCL8 might potentiate immunosuppressive activity of MSCs in a paracrine fashion. Our study documents a previously unrecognized therapeutic mechanism of MSCs in nephritis.

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Section: Introductionmentioning

confidence: 99%

“…MSCs also increase the proliferation and functions of Tregs. Overall, these properties of MSCs make them good candidates for the treatment of SLE 11 .…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells enhance CCL8 expression by podocytes in lupus-prone MRL.Faslpr mice

Kim

Lee

Kim

et al. 2023

Sci Rep

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“…In the process of organ development, disease, repair, and regeneration, the cell density in tissues changes greatly [ 9 ]. Studies have shown that the change in cell density has biological significance.…”

Section: Introductionmentioning

confidence: 99%

Osteogenic Differentiation Effect of Human Periodontal Ligament Stem-Cell Initial Cell Density on Autologous Cells and Human Bone Marrow Stromal Cells

Wang

Qiao

Sun

et al. 2023

IJMS

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Stem cells have differentiation and regulation functions. Here, we discussed the impact of cell culture density on stem cell proliferation, osteoblastogenesis, and regulation. To discuss the effect of the initial culture density of human periodontal ligament stem cells (hPDLSCs) on the osteogenic differentiation of autologous cells, we found that the hPDLSC proliferation rate decreased with an increase in the initial plating density (0.5–8 × 104 cells/cm2) for the 48 h culture cycle. After hPDLSCs induced osteogenic differentiation for 14 days with different initial cell culture densities, the expression of osteoprotegerin (OPG) and runt-related transcription factor 2(RUNX2) and the OPG/ Receptor Activator of Nuclear Factor-κ B Ligand (RANKL) ratio were the highest in the hPDLSCs initially plated at a density of 2 × 104 cells/cm2, and the average cell calcium concentration was also the highest. To study hPDLSCs regulating the osteoblastic differentiation of other cells, we used 50 μg/mL of secreted exosomes derived from hPDLSCs cultured using different initial cell densities to induce human bone marrow stromal cell (hBMSC) osteogenesis. After 14 days, the results indicated that the gene expression of OPG, Osteocalcin(OCN,)RUNX2, and osterix and the OPG/RANKL ratio were the highest in the 2 × 104 cells/cm2 initial cell density group, and the average calcium concentration was also the highest. This provides a new idea for the clinical application of stem cell osteogenesis.

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Biophysical cues to improve the immunomodulatory capacity of mesenchymal stem cells: The progress and mechanisms

Gao¹,

Jia²,

Li³

et al. 2023

Biomedicine & Pharmacotherapy

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Improving the immunomodulatory function of mesenchymal stem cells by defined chemical approach

Cited by 3 publications

References 59 publications

Mesenchymal stem cells enhance CCL8 expression by podocytes in lupus-prone MRL.Faslpr mice

Mesenchymal stem cells enhance CCL8 expression by podocytes in lupus-prone MRL.Faslpr mice

Osteogenic Differentiation Effect of Human Periodontal Ligament Stem-Cell Initial Cell Density on Autologous Cells and Human Bone Marrow Stromal Cells

Biophysical cues to improve the immunomodulatory capacity of mesenchymal stem cells: The progress and mechanisms

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