The 3D HuBioGEM Culture System
Tumor microenvironment involves active cell-cell and cell-matrix interactions via biochemical, genomic, and mechanical signaling factors. A number of synthetic (hydrogels) and animal-derived (EHS-gels) matrix scaffolds have been developed for three-dimensional (3D) cell culture studies.
Vivo Biosciences (VBI) has recently created a human biomatrix, the HuBiogel™, which provides many compositional and functional advantages. In particular, i) HuBiogel’s natural extracellular matrix (ECM) contains Col-I, laminin, Col-IV, Col-III, entactin, and HSPG but lacks all major known growth factors, ii) it is neither angiogenic nor mitogenic, rather promoting cell growth and differentiation via local growth factor signals, and iii) it allows long-term culture of single or multiple cell types, essential for producing tissue-like culture systems.
In a joint R&D program between VBI and Global Cell Solutions (GCS), a new HuBioGEM matrix was developed combining the HuBiogel with magnetic GEM™ microcarriers (75–150 um). The combination allows for not only the ideal biomimetic environment, but also magnetic manipulation for easier culture maintenance and scalability.
As outlined in Figure 1, the selected tumor is encapsulated in the HuBioGEM (2–4 mm) and then cultured in large numbers in single or multiple positions using the Wiggler™. Unlike a multiwell plate or flask, a single Wiggler position can maintain up to a 100 tumors all while using the magnetic property to quickly change out and add new media and supplements.
Typical 3D microtumors exhibit high viability (Calcein-AM green), multicellular organization (H&E, IHC), and long-term growth profiles (>14 days). Based on the proven benefits of GEM microcarriers, this 3D culture technology will allow real-time imaging, easy media exchange, drug treatment, and sample harvesting protocols.
An important advantage of the HuBioGEM system over spheroid models is that multiple cell types of defined phenotype or biology can be co-cultured in our 3D bioscaffolds to mimic in vivo-like tissue environments. In fact, 3D heterotypic constructs have also been developed using human tumor cell lines co-cultured with stromal, endothelial, immune, and progenitor cells for studying tumor invasion, angiogenesis, and hypoxia processes.