3D bioprinted glioma stem cells for brain tumor model and applications of drug susceptibility

Abstract

Glioma is still difficult to treat because of its high malignancy, high recurrence rate, and high resistance to anticancer drugs. An alternative method for research of gliomagenesis and drug resistance is to use in vitro tumor model that closely mimics the in vivo tumor microenvironment. In this study, we established a 3D bioprinted glioma stem cell model, using modified porous gelatin/alginate/fibrinogen hydrogel that mimics the extracellular matrix. Glioma stem cells achieved a survival rate of 86.92%, and proliferated with high cellular activity immediately following bioprinting. During the in vitro culture period, the printed glioma stem cells not only maintained their inherent characteristics of cancer stem cells (Nestin), but also showed differentiation potential (glial fibrillary acidic protein and β-tubulin III). In order to verify the vascularization potential of glioma stem cells, tumor angiogenesis biomarker, vascular endothelial growth factor was detected by immunohistochemistry, and its expression increased from week one to three during the culture period. Drug-sensitivity results showed that 3D printed tumor model was more resistant to temozolomide than 2D monolayer model at TMZ concentrations of 400-1600 μg ml. In summary, 3D bioprinted glioma model provides a novel alternative tool for studying gliomagenesis, glioma stem cell biology, drug resistance, and anticancer drug susceptibility in vitro.

Microscale Architecture in Biomaterial Scaffolds for Spatial Control of Neural Cell Behavior

“…Encapsulated NSCs had an initial cell viability of ~75% and were able to differentiate into neurons and glial cells. Similar results were found with a bioink of sodium alginate, fibrinogen, and gelatin (Dai et al, 2016). The bioink was soaked in calcium chloride and thrombin solutions after printing to crosslink the sodium alginate and fibrinogen components, respectively.…”

Coaxial 3D bioprinting of self-assembled multicellular heterogeneous tumor fibers

“…bioprinted Hela cells with gelatin/alginate/fibrinogen hydrogel and found that MMP-2 and MMP-9 expression of tumor cells in hydrogel were higher than those of the 2D control 16 . Previously, we have bioprinted a brain tumor model by extruding glioma stem cells-laden hydrogel 17 . But it is known that solid tumor contains not only tumor cells but also a variety of stromal cells, which are the important sources of extracellular matrix and cytokines.…”

3D Miniaturization of Human Organs for Drug Discovery

“…High-throughput pharmacological study [36,78] 3D bioprinting Primary feline H1 cardiomyocytes First rhythmic beating of 3D printed structure [93][94][95] Lung Microfabrication Epithelial cells Use of porous membrane to mimic lung functions [31,37] 3D bioprinting A549 cells and EA hy926 cells World's first 3D bioprinted lung tissue [101] Bone 3D bioprinting BMSCs High viability in microextrusion-based bioprinting [108,109,158,159] Cancer Self-assembled Intestinal stem cells Discovery of LGR5+ intestinal stem cells [52,62] Microfabrication Breast cancer cells Perfusable human microvascularized bone-mimicking (BMi) microenvironment [81,168] 3D bioprinting OVCAR-5 and MRC-5 cells Insight into complex cell-cell communication in 3D [113][114][115][116][117] Multi Self-assembled Liver, gut, vessel cells High throughput hanging drop [30,[49][50][51][52] Microfabrication Liver, heart, and vessel cells Automated control of perfusion [11,19,27,32] 3D bioprinting NPC and HCT-116 cells Multiorgan bioprinted model [30,122] a)…”

“…[116] In summary, 3D bioprinted glioma model provides a novel alternative tool for studying glioma genesis, glioma stem cell biology, drug resistance, and glioma anticancer drug susceptibility in vitro. [115] Other groups have generated different cancer 3D in vitro models including models for bone and breast cancers using 3D bioprinting. [116,117] …”