A functional three-dimensional microphysiological human model of myeloma bone disease

Area of Science:

• Biomedical Engineering
• Skeletal Biology
• Cancer Biology

Background:

• Human myeloma bone disease (MBD) disrupts skeletal remodeling by promoting osteolytic lesions and fractures.
• Existing bone models are limited for studying MBD and therapeutic effects.
• MBD involves malignant plasma cells interacting with bone marrow stromal cells, suppressing bone formation and increasing resorption.

Purpose of the Study:

• To develop a well-characterized three-dimensional (3D) bone organoid model.
• To enable the study of MBD pathogenesis and therapeutic interventions.
• To create a functional in vitro model for screening potential MBD treatments.

Main Methods:

• Osteoblasts (OBs) mineralized an extracellular matrix (ECM) to form bone-like tissue.
• Osteoclasts (OCs) were introduced to establish a normal bone remodeling model (3D-NBF).
• A human multiple myeloma (MM) cell line was added to create the 3D-MBD organoid.

Main Results:

• The 3D-MBD model showed reduced hydroxyapatite (HA), increased osteoclast activity (TRAcP-5b, CTX-1), and decreased osteoblast gene expression.
• Therapeutic agents (immunomodulatory drug, bisphosphonate, monoclonal antibody) restored HA content and reduced CTX-1 in a dose-dependent manner.
• The model successfully recapitulated MBD-associated bone metabolism imbalance.

Conclusions:

• A functional 3D organoid model of MBD was successfully developed.
• This novel model serves as a tool for studying MBD mechanisms.
• The model can be used to screen and evaluate potential therapeutics for MBD.