Uncovering the Secretome of Senescent Fibroblasts with CodePlex

Accelerate Your Workflows by Automating Data Acquisition & Analysis

The development of cancer immunotherapies and combination therapies has become more difficult with the competitive nature of the field. Navigating the space can also be a challenge with companies and academic institutions competing to develop the best candidate. IsoPlexis is helping leaders accelerate their workflows to provide the edge needed in this competitive atmosphere.  IsoPlexis’ platform helps researchers worldwide maximize their workflow efficiency. With just one system—the IsoLight—all proteomic needs are integrated and completely automated, from highly multiplexed bulk ELISA to single-cell proteomic analysis.

The IsoLight is Your Hub for Automated and Highly Multiplexed ELISA Workflows

CodePlex Secretome, one of IsoPlexis’ newest solutions, is the first fully automated hands-off solution for obtaining highly multiplexed bulk cytokine data with only five minutes of hands-on sample loading time. Read more about this novel solution in our previous CodePlex Secretome blog post.

The newly released population-based CodePlex Secretome solution can be used to generate multiplexed serum-level data, and optimize experimental conditions quickly and cost-efficiently. This chip runs on the award-winning IsoLight system, so the entire highly-multiplexed ELISA workflow is fully automated within the IsoLight. Not only does this mean less hands-on time, it also means that all data analysis is fully-automated with IsoPlexis’ integrated software suite, IsoSpeak, which processes the sample data and transforms complex data into easy to understand advanced visualizations.

In our previous post on CodePlex Secretome, we discussed how researchers used this technology to identify the soluble factors responsible for controlling cell-density-dependent migration, thought to be driving cell metastasis. CodePlex technology was used to analyze the secretomic profiles of cells ingrained in three-dimensional models at high and low densities with its multiplexed antibody microarray assay, which simultaneously measured the concentration of 24 soluble molecules. CodePlex technology revealed that both IL-6 and IL-8 were secreted at a high concentration, which drove cell migration in these models. With cytokine profiling, this study identified a potential therapy with the ability to inhibit metastasis and improve cancer patient outcomes.1

Applying CodePlex Beyond Cancer Therapy to Cellular Senescence

Many areas, such as immunotherapy and regenerative medicine, have shown interest in the controlled delivery of cytokines and growth factors, and with this study from Xiao et al.,2 researchers have shown that “applying senescent fibroblasts to wound repair in vivo leads to increased blood flow in [a] diabetic mouse model. Together, the work points to a new direction for modeling the delivery of cytokines and growth factors that promote microvascular tissue engineering and tissue repairs.”2

Researchers in the study engineered “senescent primary human lung fibroblasts as a living source of cytokines and growth factors to promote in vitro growth of microvasculature as well as to demonstrate the potential applications.”2 Recent studies have demonstrated that cellular senescence may offer a way to address the various challenges associated with delivering growth factors and cytokines for microvascular engineering. Outside stressors like chemotherapy and radiation can induce cellular senescence, which can then make it possible to complete “in vitro engineering of cytokine-secreting cells prior to in vivo therapeutic applications.”2

Xiao et al. used IsoPlexis’ CodePlex technology to measure the intensity of 14 soluble factors of both presenescent and senescent fibroblasts. Both IL-6 and IL-8 were found to be the most prominent cytokines secreted in the senescent fibroblasts, but when comparing the senescent fibroblasts collected on day 2, day 4, and day 6 after treatment with bleomycin, “IL-6 increased as the number of cells decreased. This indicates that a subpopulation of senescent fibroblasts expresses IL-6 at high levels.”2  Overall, the growth factor production from senescent primary lung fibroblasts was significantly increased compared to the presenescent fibroblasts, which demonstrates the potential in using “these engineered cells as a source of proangiogenic factors to promote microvasculature formation in vitro and in vivo.”2

This work reveals proteomic insights into cellular senescence and identifies a new possible path for the delivery of growth factors and cytokines that can encourage microvascular tissue engineering and tissue repairs.2 Researchers also showed the use of senescent fibroblasts in diabetic wound repair to increase blood flow in vivo.

Download our latest CodePlex Tech Note and CodePlex eBook to learn more about this innovative new solution. Speak to an expert today to see how CodePlex and IsoPlexis’ other solutions can optimize your existing workflow.

References:

  1. Jayatilaka H, et al. Synergistic IL-6 and IL-8 paracrine signalling pathway infers a strategy to inhibit tumour cell migration. Nature Communications 8: 15584, 2017.
  2. Xiao Y, et al. Senescent Cells with Augmented Cytokine Production for Microvascular Bioengineering and Tissue Repairs. Advanced Biosystems 3: 1900089, 2019.
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