An in vitro model of granuloma formation using human peripheral blood mononuclear cells (PBMCs) derived from patients with active sarcoidosis or latent tuberculosis infection (LTBI).



The Need

The immuopathogeneis of sarcoidosis is poorly understood and the exact cause of the disease is unknown. Foreign substances “trigger” the body's immune system, but the abnormal response generated results in formation of granulomas. The cause of this reaction is unknown and no data has been able to consistently and convincingly established definitive connections to the disease cause. New and relevant laboratory models that represent the complexity and diversity of human sarcoidosis and tuberculosis diseases may help improve diagnostic care and treatments for these complex medical issues.

The Technology

Researchers at The Ohio State University led by Dr. Elliott Crouser have developed an in vitro model of granuloma formation using human peripheral blood mononuclear cells (PBMCs) derived from normal healthy control subjects or patients with either active sarcoidosis or latent tuberculosis infection (LTBI). This model recapitulates molecular mechanisms that correspond to diseased human tissue and allows for the exploration of early granuloma formation mechanisms.

To develop the model, polystyrene beads were coated with purified protein derivative or human serum albumin. These beads are fluorescently-labeled, mono-dispersed, and can be covalently coupled with proteins. Following coating and preparation, beads were cultured with cells derived from patients and following a period of incubation, cells were evaluated for granuloma formation. The molecular profiles of these aggregates had significantly different expression patterns, which revealed distinct pathways for sarcoidosis and LTBI. This novel in vitro model could be utilized to differentiate between these diseases, thus improving diagnosis and treatment for patients.

Commercial Applications

  • Drug development
  • Clinical research

Benefits/ Advantages

  • This novel in vitro human granuloma model is proposed as a tool to investigate mechanisms of early granuloma formation and for preclinical drug discovery research of human granulomatous disorders.
  • The model can be used for biomarker discovery, exploration of disease mechanisms, and for preclinical testing of novel therapeutics.
  • This bead coated technology can be utilized in research or clinical settings to help diagnose sarcoidosis or LTBI at an earlier stage, improving drug mechanism of action studies and potentially improving treatment for patients

References

  • Crouser, E.D.; White, P; Caceres, E.G.; et al. Am J. Resp. Cell Molecular Bio. 2017.
  • Hao, W; Schlesinger, L.S; Friedman, A. PLOSone. 2016.



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