Microarrayed human bone marrow organoids for modeling blood stem cell dynamics

Zidi

et al. 2023

Cells

Self Cite

Spheroids and organoids are important novel players in medical and life science research. They are gradually replacing two-dimensional (2D) cell cultures. Indeed, three-dimensional (3D) cultures are closer to the in vivo reality and open promising perspectives for academic research, drug screening, and personalized medicine. A large variety of cells and tissues, including tumor cells, can be the starting material for the generation of 3D cultures, including primary tissues, stem cells, or cell lines. A panoply of methods has been developed to generate 3D structures, including spontaneous or forced cell aggregation, air–liquid interface conditions, low cell attachment supports, magnetic levitation, and scaffold-based technologies. The choice of the most appropriate method depends on (i) the origin of the tissue, (ii) the presence or absence of a disease, and (iii) the intended application. This review summarizes methods and approaches for the generation of cancer spheroids and organoids, including their advantages and limitations. We also highlight some of the challenges and unresolved issues in the field of cancer spheroids and organoids, and discuss possible therapeutic applications.

Section: Current Source To Generate and Culture In Vitro Tumor Sphero...mentioning

confidence: 99%

Section: Current Source To Generate and Culture In Vitro Tumor Sphero...mentioning

confidence: 99%

Cancer Spheroids and Organoids as Novel Tools for Research and Therapy: State of the Art and Challenges to Guide Precision Medicine

Zidi

et al. 2023

Cells

Self Cite

ACS Appl. Mater. Interfaces

“…PEG-based microwells are increasingly used for generating spheroids. For example, Lutolf and colleagues built an organoid array technology using PEG-based microwells, 66 which were generated using silicon-based soft lithography and PDMS molding. The PDMS molds were then used to imprint thiol-vinylsulfone hydrogel cross-linking (gelatin time ∼15 min).…”

Section: Optimization Of Visible Light-initiated Thiol−mentioning

confidence: 99%

Poly(ethylene glycol)–Norbornene as a Photoclick Bioink for Digital Light Processing 3D Bioprinting

Kim

Lin

2023

Digital light processing (DLP) bioprinting is an emerging technology for three-dimensional bioprinting (3DBP) owing to its high printing fidelity, fast fabrication speed, and higher printing resolution. Low-viscosity bioinks such as poly(ethylene glycol) diacrylate (PEGDA) are commonly used for DLP-based bioprinting. However, the cross-linking of PEGDA proceeds via chain-growth photopolymerization that displays significant heterogeneity in cross-linking density. In contrast, step-growth thiol–norbornene photopolymerization is not oxygen inhibited and produces hydrogels with an ideal network structure. The high cytocompatibility and rapid gelation of thiol–norbornene photopolymerization have lent itself to the cross-linking of cell-laden hydrogels but have not been extensively used for DLP bioprinting. In this study, we explored eight-arm PEG–norbornene (PEG8NB) as a bioink/resin for visible light-initiated DLP-based 3DBP. The PEG8NB-based DLP resin showed high printing fidelity and cytocompatibility even without the use of any bioactive motifs and high initial stiffness. In addition, we demonstrated the versatility of the PEGNB resin by printing solid structures as cell culture devices, hollow channels for endothelialization, and microwells for generating cell spheroids. This work not only expands the selection of bioinks for DLP-based 3DBP but also provides a platform for dynamic modification of the bioprinted constructs.

“…In essence, the bone marrow niche represents a special type of blood vessel, and recent studies aimed at recapitulating the development of this environment in vitro. For instance, Giger et al 89 used a microwell-based approach where they coseeded ECs and mesenchymal stem cells to form a spheroid. By performing several titration experiments with regard to mesenchymal stem cells:ECs ratios, the authors showed that the number of self-renewing mesenchymal stem cells was higher in the dual-cell type organoids and thus depended on the presence of ECs.…”

Section: Organotypic Vasculature and Specific Functionsmentioning

confidence: 99%

Blood Vessel Organoids for Development and Disease

Salewskij

Penninger

2023

Circulation Research

Despite enormous advances, cardiovascular disorders are still a major threat to global health and are responsible for one-third of deaths worldwide. Research for new therapeutics and the investigation of their effects on vascular parameters is often limited by species-specific pathways and a lack of high-throughput methods. The complex 3-dimensional environment of blood vessels, intricate cellular crosstalks, and organ-specific architectures further complicate the quest for a faithful human in vitro model. The development of novel organoid models of various tissues such as brain, gut, and kidney signified a leap for the field of personalized medicine and disease research. By utilizing either embryonic- or patient-derived stem cells, different developmental and pathological mechanisms can be modeled and investigated in a controlled in vitro environment. We have recently developed self-organizing human capillary blood vessel organoids that recapitulate key processes of vasculogenesis, angiogenesis, and diabetic vasculopathy. Since then, this organoid system has been utilized as a model for other disease processes, refined, and adapted for organ specificity. In this review, we will discuss novel and alternative approaches to blood vessel engineering and explore the cellular identity of engineered blood vessels in comparison to in vivo vasculature. Future perspectives and the therapeutic potential of blood vessel organoids will be discussed.