Dataset Information

Transplanted interleukin-4--secreting mesenchymal stromal cells show extended survival and increased bone mineral density in the murine femur.

ABSTRACT: BACKGROUND:Mesenchymal stromal cell (MSC)-based therapy has great potential to modulate chronic inflammation and enhance tissue regeneration. Crosstalk between MSC-lineage cells and polarized macrophages is critical for bone formation and remodeling in inflammatory bone diseases. However, the translational application of this interaction is limited by the short-term viability of MSCs after cell transplantation. METHODS:Three types of genetically modified (GM) MSCs were created: (1) luciferase-expressing reporter MSCs; (2) MSCs that secrete interleukin (IL)-4 either constitutively; and (3) MSCs that secrete IL-4 as a response to nuclear factor kappa-light-chain-enhancer of activated B cell (NF?B) activation. Cells were injected into the murine distal femoral bone marrow cavity. MSC viability and bone formation were examined in vivo. Cytokine secretion was determined in a femoral explant organ culture model. RESULTS:The reporter MSCs survived up to 4 weeks post-implantation. No difference in the number of viable cells was found between high (2.5?×?106) and low (0.5?×?106) cell-injected groups. Injection of 2.5?×?106 reporter MSCs increased local bone mineral density at 4 weeks post-implantation. Injection of 0.5?×?106 constitutive IL-4 or NF?B-sensing IL-4-secreting MSCs increased bone mineral density at 2 weeks post-implantation. In the femoral explant organ culture model, LPS treatment induced IL-4 secretion in the NF?B-sensing IL-4-secreting MSC group and IL-10 secretion in all the femur samples. No significant differences in tumor necrosis factor (TNF)? and IL-1? secretion were observed between the MSC-transplanted and control groups in the explant culture. DISCUSSION:Transplanted GM MSCs demonstrated prolonged cell viability when transplanted to a compatible niche within the bone marrow cavity. GM IL-4-secreting MSCs may have great potential to enhance bone regeneration in disorders associated with chronic inflammation.

SUBMITTER: Lin T

PROVIDER: S-EPMC6379084 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Transplanted interleukin-4--secreting mesenchymal stromal cells show extended survival and increased bone mineral density in the murine femur.

Lin Tzuhua T Pajarinen Jukka J Kohno Yusuke Y Maruyama Masahiro M Romero-Lopez Monica M Huang Jhih-Fong JF Nathan Karthik K Khan Tahsin N TN Yao Zhenyu Z Goodman Stuart B SB

Cytotherapy 20180802 8

<h4>Background</h4>Mesenchymal stromal cell (MSC)-based therapy has great potential to modulate chronic inflammation and enhance tissue regeneration. Crosstalk between MSC-lineage cells and polarized macrophages is critical for bone formation and remodeling in inflammatory bone diseases. However, the translational application of this interaction is limited by the short-term viability of MSCs after cell transplantation.<h4>Methods</h4>Three types of genetically modified (GM) MSCs were created: (1 ...[more]

PMID: 30077567

Similar Datasets

Project description:Bone mineral density (BMD) has been linked to mortality, but little is known about the independent contribution of each endosteal bone compartment and also the rate of bone loss to risk of mortality. We examined the relationships between (1) baseline trabecular and cortical volumetric BMD (vBMD) at the proximal femur, and (2) the rate of trabecular and cortical bone loss and all-cause mortality in older adults from the AGES-Reykjavik study. The analysis of trabecular and cortical vBMD and mortality was based on the baseline cohort of 4654 participants (aged ≥66 years) with a median follow-up of 9.4 years; the association between rate of bone loss and mortality was based on 2653 participants with bone loss data (median follow-up of 5.6 years). Analyses employed multivariable Cox-proportional models to estimate hazard ratios (HRs) with time-varying fracture status; trabecular and cortical variables were included together in all models. Adjusted for important confounders, Cox models showed that participants in the lowest quartile of trabecular vBMD had an increased risk of mortality compared to participants in other quartiles (HR = 1.12; 95% confidence interval (CI), 1.01 to 1.25); baseline cortical vBMD was not related to mortality (HR = 1.08; 95% CI, 0.97 to 1.20). After adjustment for time-dependent fracture status, results were attenuated and not statistically significant. A faster loss (quartile 1 versus quartiles 2-4) in both trabecular and cortical bone was associated with higher mortality risk (HR = 1.37 and 1.33, respectively); these associations were independent of major potential confounders including time-dependent incident fractures (HR = 1.32 and 1.34, respectively). Overall, data suggest that faster bone losses over time in both the trabecular and cortical bone compartments are associated with mortality risk and that measurements of change in bone health may be more informative than single-point measurements in explaining mortality differences in older adults. © 2017 American Society for Bone and Mineral Research.

Dataset Information

Transplanted interleukin-4--secreting mesenchymal stromal cells show extended survival and increased bone mineral density in the murine femur.

Publications

Transplanted interleukin-4--secreting mesenchymal stromal cells show extended survival and increased bone mineral density in the murine femur.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets