Immunological substance testing on human lymphatic micro-organoids in vitro

Area of Science:

• Immunology
• Biotechnology
• Drug Development

Background:

• Pharmaceuticals can cause adverse immuno-toxicological effects.
• Current in vitro and animal models inadequately predict human immune responses to drugs.
• Existing cell cultures and tissue biopsies have significant limitations for long-term immune studies.

Purpose of the Study:

• To develop an advanced in vitro model that accurately mimics human lymph node function.
• To enable long-term assessment of drug-induced cellular and humoral immune responses.
• To overcome the limitations of existing models for predicting drug immunotoxicity.

Main Methods:

• Constructed a 3D micro-organoid model (HuALN) using peripheral blood mononuclear cells (PBMCs) and stromal cells within biogenic/artificial scaffolds.
• Cultured the HuALN model for several weeks to allow for long-term and repeated drug exposure.
• Monitored cellular immunity via cytokine release and humoral immunity via B cell activation, plasma cell formation, and antibody secretion (IgM, IgG).
• Analyzed cellular composition and micro-organoid formation using flow cytometry, histology, and in situ imaging.

Main Results:

• The HuALN model successfully mimicked key structures of secondary lymphatic organs.
• The model supported long-term culture and repeated drug exposure, enabling monitoring of immune responses.
• Distinct patterns of cellular and humoral immunity were observed in response to drug exposure.

Conclusions:

• The human lymph node micro-organoid (HuALN) model provides a novel, advanced platform for in vitro drug immunotoxicity testing.
• This model overcomes limitations of traditional methods, offering a more predictive assessment of drug safety.
• The HuALN model facilitates comprehensive analysis of both cellular and humoral immune responses to pharmaceutical compounds.