In Vitro Modeling of Non-Solid Tumors: How Far Can Tissue Engineering Go?

Area of Science:

• Hematological malignancies
• Cancer biology
• Tissue engineering

Background:

• Malignant cells in hematological cancers like leukemia and myeloma home to the bone marrow (BM) niche.
• The BM microenvironment significantly influences cancer development and drug resistance.
• Existing in vitro models struggle to replicate the complexity of the native BM niche.

Purpose of the Study:

• To review current in vitro models for simulating the bone marrow (BM) niche in hematological malignancies.
• To identify key variables for improving the fidelity of engineered BM models.
• To discuss the relevance of model complexity for predicting drug responses in blood cancers.

Main Methods:

• Literature review of existing in vitro bone marrow (BM) models.
• Analysis of factors influencing BM microenvironment complexity.
• Discussion of tissue engineering strategies for model development.

Main Results:

• Current in vitro BM models capture some aspects of the native niche but lack crucial complexity.
• Variables like extracellular matrix, topography, vascularization, and cellular composition are critical for model relevance.
• Fully humanized platforms mimicking natural interactions remain a significant challenge.

Conclusions:

• Improved in vitro BM models are essential for understanding non-solid tumor biology and niche regulation.
• Tissue engineering offers rational approaches to define variables for more accurate models.
• The extent to which model complexity is necessary for reliable drug response prediction is debated but advances personalized medicine.