Why Do We Need a New Pre-Clinical Model in Multiple Myeloma
Multiple Myeloma (MM) is the second most prevalent hematological malignancy and causes approximately 20% of deaths from hematological malignancies. Despite the significant efficacy of novel therapies to eradicate MM in vitro and in animal models, many MM patients (especially in relapsed setting) fail to respond to therapy.
Potential Problems in “Classic” Drug Discovery Models
The discrepancy between the laboratory models and the shortcoming clinical efficacy may be related to that the classic tissue culture models: (a) use of cultures of cancer cell lines alone, neglecting the vital role of the bone marrow microenvironment; (b) fail to recapitulate the three-dimensional (3D) structure of the tissue with oxygen and drug gradients in the depth of the tissue; and (c) rely on a limited number of cell lines that fail to reflect the heterogeneity between patients.
Our Novel 3D Tissue Engineered Bone Marrow (3DTEBM) Model
We have developed a novel patient-derived 3D tissue engineered bone marrow (3DTEBM) model based on patient material, no additional exogenous material was added. It is based on the crosslinking of Fibrinogen which is naturally found in the BM supernatant. Not only the cancer cells were included, but also all the other accessory cells in the bone marrow micro-environment.
The 3DTEBM was shown to demonstrate the interactions of MM cells with their malignant microenvironment, simulate 3D aspects of the BM niche, and reflect individual heterogeneity in progression and response to therapy in MM patients.
Recreating the Bone Marrow Niche
Unlike any other available 3D-cell culture system, the 3DTEBM allowed the proliferation of primary MM cells ex vivo
Applications of the 3DTEBM Model
The 3DTEBM technology provides an improved model for understanding tumor biology and drug resistance of MM in the context of the malignant BM microenvironment; and it provides personalized prediction of therapeutic efficacy in individual MM patients.
Furthermore, current studies are conducted to expand the use of the 3DTEBM to other hematologic malignancies and solid tumors.
This technology is patented, with an exclusive license to Cellatrix LLC.