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1. Ethical Dimensions of Human Organoids Research

   https://doi.org/10.1525/abt.2021.83.9.575  

   Gomez-Jones, Tashaé; Kao, Robert M (November 2021, The American Biology Teacher)

   Over the past decade, the development of three-dimensional mammalian cell organization—called human organoids—from stem cells has provided a framework for future clinical therapies. As human organoid research progresses, we also need to keep in mind the cross-cultural and ethical dimensions of human organoids research. Our review article aims to examine the ethical dimensions of cerebral human organoids and provide an ethical framework guide within human organoids research. 

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2. Spatially controlled construction of assembloids using bioprinting

   https://doi.org/10.1038/s41467-023-40006-5  

   Roth, Julien G.; Brunel, Lucia G.; Huang, Michelle S.; Liu, Yueming; Cai, Betty; Sinha, Sauradeep; Yang, Fan; Pașca, Sergiu P.; Shin, Sungchul; Heilshorn, Sarah C. (December 2023, Nature Communications)

   Abstract The biofabrication of three-dimensional (3D) tissues that recapitulate organ-specific architecture and function would benefit from temporal and spatial control of cell-cell interactions. Bioprinting, while potentially capable of achieving such control, is poorly suited to organoids with conserved cytoarchitectures that are susceptible to plastic deformation. Here, we develop a platform, termed Spatially Patterned Organoid Transfer (SPOT), consisting of an iron-oxide nanoparticle laden hydrogel and magnetized 3D printer to enable the controlled lifting, transport, and deposition of organoids. We identify cellulose nanofibers as both an ideal biomaterial for encasing organoids with magnetic nanoparticles and a shear-thinning, self-healing support hydrogel for maintaining the spatial positioning of organoids to facilitate the generation of assembloids. We leverage SPOT to create precisely arranged assembloids composed of human pluripotent stem cell-derived neural organoids and patient-derived glioma organoids. In doing so, we demonstrate the potential for the SPOT platform to construct assembloids which recapitulate key developmental processes and disease etiologies. 

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3. Stretchable Mesh Nanoelectronics for 3D Single‐Cell Chronic Electrophysiology from Developing Brain Organoids

   https://doi.org/10.1002/adma.202106829  

   Le Floch, Paul; Li, Qiang; Lin, Zuwan; Zhao, Siyuan; Liu, Ren; Tasnim, Kazi; Jiang, Han; Liu, Jia (March 2022, Advanced Materials)

   Abstract Human induced pluripotent stem cell derived brain organoids have shown great potential for studies of human brain development and neurological disorders. However, quantifying the evolution of the electrical properties of brain organoids during development is currently limited by the measurement techniques, which cannot provide long‐term stable 3D bioelectrical interfaces with developing brain organoids. Here, a cyborg brain organoid platform is reported, in which “tissue‐like” stretchable mesh nanoelectronics are designed to match the mechanical properties of brain organoids and to be folded by the organogenetic process of progenitor or stem cells, distributing stretchable electrode arrays across the 3D organoids. The tissue‐wide integrated stretchable electrode arrays show no interruption to brain organoid development, adapt to the volume and morphological changes during brain organoid organogenesis, and provide long‐term stable electrical contacts with neurons within brain organoids during development. The seamless and noninvasive coupling of electrodes to neurons enables long‐term stable, continuous recording and captures the emergence of single‐cell action potentials from early‐stage brain organoid development. 

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4. Brown Adipose Tissue as a Unique Niche for Islet Organoid Transplantation: Insights From In Vivo Imaging

   https://doi.org/10.1097/TXD.0000000000001658  

   Sun, Aixia; Hayat, Hanaan; Kenyon, Elizabeth; Quadri, Tahnia; Amos, Darius; Perkins, Keenan; Nigam, Saumya; Tarleton, Deanna; Mallett, Christiane L; Deng, Cheri X; et al (January 2024, Transplantation Direct)

   Background.Transplantation of human-induced pluripotent stem cell (hiPSC)-derived islet organoids is a promising cell replacement therapy for type 1 diabetes (T1D). It is important to improve the efficacy of islet organoids transplantation by identifying new transplantation sites with high vascularization and sufficient accommodation to support graft survival with a high capacity for oxygen delivery. Methods.A human-induced pluripotent stem cell line (hiPSCs-L1) was generated constitutively expressing luciferase. Luciferase-expressing hiPSCs were differentiated into islet organoids. The islet organoids were transplanted into the scapular brown adipose tissue (BAT) of nonobese diabetic/severe combined immunodeficiency disease (NOD/SCID) mice as the BAT group and under the left kidney capsule (KC) of NOD/SCID mice as a control group, respectively. Bioluminescence imaging (BLI) of the organoid grafts was performed on days 1, 7, 14, 28, 35, 42, 49, 56, and 63 posttransplantation. Results.BLI signals were detected in all recipients, including both the BAT and control groups. The BLI signal gradually decreased in both BAT and KC groups. However, the graft BLI signal intensity under the left KC decreased substantially faster than that of the BAT. Furthermore, our data show that islet organoids transplanted into streptozotocin-induced diabetic mice restored normoglycemia. Positron emission tomography/MRI verified that the islet organoids were transplanted at the intended location in these diabetic mice. Immunofluorescence staining revealed the presence of functional organoid grafts, as confirmed by insulin and glucagon staining. Conclusions.Our results demonstrate that BAT is a potentially desirable site for islet organoid transplantation for T1D therapy. 

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5. Controlling Morphology and Functions of Cardiac Organoids by Two-Dimensional Geometrical Templates

   https://doi.org/10.1159/000521787  

   Hoang, Plansky; Sun, Shiyang; Tarris, Bearett A.; Ma, Zhen (March 2023, Cells Tissues Organs)

   Traditionally, tissue-specific organoids are generated as 3D aggregates of stem cells embedded in Matrigel or hydrogels, and the aggregates eventually end up a spherical shape and suspended in the matrix. Lack of geometrical control of organoid formation makes these spherical organoids limited for modeling the tissues with complex shapes. To address this challenge, we developed a new method to generate 3D spatial-organized cardiac organoids from 2D micropatterned human induced pluripotent stem cell (hiPSC) colonies, instead of directly from 3D stem cell aggregates. This new approach opens the possibility to create cardiac organoids that are templated by 2D non-spherical geometries, which potentially provides us a deeper understanding of biophysical controls on developmental organogenesis. Here, we designed 2D geometrical templates with quadrilateral shapes and pentagram shapes that had same total area but different geometrical shapes. Using this templated substrate, we grew cardiac organoids from hiPSCs and collected a series of parameters to characterize morphological and functional properties of the cardiac organoids. In quadrilateral templates, we found that increasing the aspect ratio impaired cardiac tissue 3D self-assembly, but the elongated geometry improved the cardiac contractile functions. However, in pentagram templates, cardiac organoid structure and function were optimized with a specific geometry of an ideal star shape. This study will shed a light on “organogenesis-by-design” by increasing the intricacy of starting templates from external geometrical cues to improve the organoid morphogenesis and functionality. 

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