مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
3D Bioprinting of Human Stem Cells for Neural Tissue Modeling and Disease Research
3D Bioprinting of Human Stem Cells for Neural Tissue Modeling and Disease Research
Yasaman Baharvand,1Arezou Arvand,2,*
1. Department of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran 2. Memorial University of Newfoundland
Introduction: Animal models are widely used for disease modeling and drug discovery, but they have limitations. They often fail to accurately predict the efficacy and toxicity of potential drug targets and cannot fully capture the complexity and variability of human neural tissues (1).Human-derived stem cells, such as mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs), provide a promising alternative. When combined with 3D bioprinting, these cells can be used to generate neural tissues for personalized medicine (1,2). MSCs can be obtained from patients and reprogrammed into neural cells, while iPSCs are reprogrammed somatic cells capable of self-renewal and differentiation into any cell type which enable the study of neurodegenerative disorders such as Alzheimer’s disease (AD) (1,2). The breakthrough discovery of iPSCs by Takahashi and Yamanaka in 2006, achieved through the introduction of transcription factors (Oct4, Sox2, cMyc, and Klf4), made it possible to model previously inaccessible patient-derived central nervous system (CNS) cells, including neurons, astrocytes, and microglia (3).
Three-dimensional (3D) cell culture methods provide major advantages over traditional 2D systems by promoting more natural cell growth, function, and differentiation through a more natural 3D architectures that mimic the in vivo environment (4). These cultures maintain normal cell shape, support essential interactions with the extracellular matrix, and reduce the artificial stress found in 2D cultures, which results in improved cell longevity and more informative microenvironments (4). 3D bioprinting also shows great potential in modeling tumor microenvironments. For example, in neuroblastoma, patient-derived cells can be used to rebuild tumor–tissue interactions, enabling personalized drug-testing platforms that optimize therapy regimens (5)
3D bioprinting is an additive manufacturing method, which combines cells and biomaterials to create tissue constructs that closely mimic in vivo conditions. Compared with traditional tissue engineering, it offers precise control over cell distribution, cost-effectiveness, and scalability (2,4,6). Scaffold-free systems such as spheroids and organoids often lack organization and mechanical stability, while scaffold-based 3D bioprinting provides porosity, structural support, and organizational control. All these benefits make it powerful for neural tissue engineering (4).
Methods: We searched trusted databases, including PubMed, Scopus, and Web of Science, for studies published from 2020 onward. Keywords included 3D bioprinting, iPSCs, MSCs, and neural tissue engineering. Relevant articles were selected based on originality, quality, and focus on recent advances in neural tissue modeling.
Results: 3D bioprinting of human-derived stem cells has shown strong potential for creating neural-like structures that more closely mimic brain physiology than traditional 2D cultures (3,4). Neural cultures derived from patient-specific or isogenic mutant iPSCs successfully replicated AD phenotypes, highlighting their use for identifying and validating drug candidates (2,7). By reproducing the in vivo environment, 3D systems supported optimal cell growth, function, and differentiation, while maintaining cell shape and fostering cell–extracellular matrix interactions, thus reducing the stress seen in 2D systems (4).
Scaffold-based 3D bioprinting addressed the limitations of scaffold-free models by providing mechanical stability, structural support, and porosity, which improved both cell viability and tissue organization (4).
Moreover, 3D bioprinted models combining endothelial cells with MSCs produced functional, perfusable vasculature in soft hydrogels. This advancement is particularly valuable for modeling tumor microenvironments in cancers such as neuroblastoma, where vascularization is crucial for tumor growth and drug-response studies (8). In glioblastoma research, 3D bioprinted organoid systems reproduced tumor architecture, microenvironmental gradients, and cellular heterogeneity that creat a platform to study interactions between glioblastoma stem cells and normal brain components(8). These bioprinted models demonstrated improved scalability and tunability of biological parameters, such as cellular composition and extracellular matrix stiffness, compared to labor-intensive, low-throughput organoid systems (8). Brain organoids, despite recapitulating early brain development, lack vasculature, limiting nutrient diffusion and causing cellular stress, though this may enhance AD-related features like Aβ aggregation (9). Transdifferentiated neural cells in 3D models retain age-related epigenetic markers and reveals early AD phenotypes and environmental contributions to pathogenesis (9).
Conclusion: Human-derived stem cells, particularly MSCs and iPSCs, combined with 3D bioprinting, offer a transformative platform for neural tissue modeling that overcomes many limitations of traditional animal models and 2D cultures. These 3D models better mimic real brain tissue than animal models or traditional 2D cultures. Overall, 3D bioprinted human neural tissues offer a patient-specific and reliable way to study brain function, disease, and potential treatments.