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

Lee

et al. 2023

Sci Rep

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.

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

Lee

et al. 2023

Sci Rep

“…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

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.

Mesenchymal Stromal Cell Immunomodulatory Potential for Orthopedic Applications can be fine-tuned via 3D nano-engineered Scaffolds

Banche-Niclot,

Lim,

McCulloch

et al. 2024

Curr Stem Cell Rep

Purpose of Review This concise review delves into the pivotal role of three-dimensional (3D) nanostructured scaffolds in fostering mesenchymal stromal cells (MSC) immunomodulatory capabilities, with a specific focus on orthopedic applications. In this ever-advancing research field, where inflammation and tissue repair are intricately linked, manipulation of the immunomodulatory properties of MSCs becomes crucial, especially for inflammatory-based diseases such as osteoarthritis (OA). The primary inquiries include the promise of nanoscale tools to revolutionize orthopedic regenerative medicine, the role of tailored design features in steering cellular immunomodulatory response, and the resulting beneficial impact on tissue regeneration. Recent Findings Recent studies demonstrate the crucial importance of precise control over 3D scaffold design at the nanoscale to maximize the efficacy of regenerative therapies. Compared to 2D, engineered 3D environments with specific chemical composition and finely tuned physical nano-features, heighten MSC secretion of immunosuppressive factors including transforming growth factor-β1 (TGF-β1), prostaglandin E2 (PGE2), indoleamine-pyrrole 2,3-dioxygenase (IDO), and interleukin-10 (IL-10), contributing to improve cartilage and osteo differentiation. Summary Nanostructured 3D scaffolds characterized by nano topography, roughness, high porosity, biomimetic stiffness and chemistry, offer a sophisticated means to optimize the immunosuppressive potential of MSCs by allowing the spatiotemporal control over signaling molecules at the nanoscale. Polymeric constructs, notably collagen-based ones, lead to heightened immunomodulatory response and superior cellular differentiation. This effect is because 3D constructs provide a biomimetic environment that enhances cell interaction, controls cell behavior, and modulates the secretion of anti-inflammatory cytokines. The integration of innovative 3D nanostructured approaches into MSC culture systems paves the way for significant strides in cell therapy, addressing current challenges in their clinical application and holding great promise for developing more effective and precise treatments for orthopedic inflammatory disorders.