Assessment of Experimental Techniques That Facilitate Human Granuloma Formation in an In Vitro System: A Systematic Review

Abstract

The process of granuloma formation is complex, and due to species differences, the validity of animal studies is somewhat questioned. Moreover, the large number of animals needed to observe the different stages of development also raises ethical questions. Therefore, researchers have explored the use of human peripheral blood mononuclear cells (PBMCs), a heterogeneous population of immune cells, in an in vitro model. This review included in vitro studies that focused on exposing PBMCs—from healthy, sensitized, or diseased individuals—to antigens derived from infectious agents—such as mycobacteria or Schistosoma spp.—or inorganic antigens—such as beryllium. The reviewed studies mainly explored how human in vitro granuloma models can contribute towards understanding the pathogenesis of granulomatous diseases, especially during the early stages of granuloma formation. The feasibility of granuloma modelling was thus largely assessed via experimental techniques including (1) granuloma scoring indices (GI), (2) cell surface markers and (3) cytokine secretion profiling. While granuloma scoring showed some similarities between studies, a large variability of culture conditions and endpoints measured have been identified. The lack of any standardization currently impedes the success of a human in vitro granuloma model.

Differential immunological effects of silica nanoparticles on peripheral blood mononuclear cells of silicosis patients and controls

“…To investigate the modulation by SiNPs and cellular morphology of granulomatous structures, we applied an ex vivo model of human silicotic micro-granulomas as described by Ganesan et al. ( 13 ). Additionally, the cytokine release profiles and immunoglobulin levels across the different exposures to SiNPs were investigated.…”

Modeling Paratuberculosis in Laboratory Animals, Cells, or Tissues: A Focus on Their Applications for Pathogenesis, Diagnosis, Vaccines, and Therapy Studies

“…Since maintaining granuloma structures in vitro over an extended period of time is still a limiting factor for this model [83], only the features of the early stage of granuloma formation can be studied. Although it has been proposed that granulomas are marked by the interaction of various immune cell types, which acquire different phenotypes through it, as is the case in the M1/M2 polarization of macrophages, to date, only small and simple granuloma-like structures based on MDMs have been evaluated as a model for PTB.…”