Applications of 3D Cell Culture in Biomedicines

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 6158

Special Issue Editor


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Guest Editor
Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan
Interests: cell therapy; regenerative therapy; cell biotechnology; 3D culture; nanoparticles; bioimaging; biobank; cryopreservation; stem cell; health technology assessment
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Special Issue Information

Dear Colleagues,

In recent years, research on the fabrication and application of living tissues and organs has been widely conducted using 3D culture (three-dimensional culture) techniques. For example, materials such as ECM (extracellular matrix) and synthetic polymers can be microfabricated to provide a favorable environment and scaffold for individual cells. In other words, a culture environment similar to a living organism (in vivo) can be reconstructed in vitro and created using MEMS (micro electro mechanical system) technology. In addition, it has been possible to induce pluripotent cells (ES cells and iPS cells) and tissue stem cells into target 3D models (brain, liver, skin, bone, cornea, cartilage, cancer, etc.) by improving culture methods and conditions. The obtained tissues and organs are expected to be applied in many fields of biomedicine, regenerative therapy, and drug discovery. Here, we call for reports on 'Applications of 3D Cell Culture in Biomedicines' in various fields of biomedicines. Examples of topics of interest include:

  • 3D cultures (culture technology, biomaterials, culture device, culture device design, simulation, etc.).
  • 3D tissue and organs (biomedicine, regenerative therapy, and drug discovery, in vitro, in vivo, ex vivo).

Therefore, this Special Issue seeks to publish high-quality articles, including original research and reviews.

Dr. Yoshitaka Miyamoto
Guest Editor

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Keywords

  • 3D cell culture
  • organoid
  • spheroid
  • stem cell
  • transplantation
  • scaffold
  • extracellular matrix
  • biomedicine
  • regenerative therapy
  • drug discovery

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Published Papers (3 papers)

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Research

13 pages, 4002 KiB  
Article
Calcium-Enhanced Medium-Based Delivery of Splice Modulating Antisense Oligonucleotides in 2D and 3D hiPSC-Derived Neuronal Models
by Ronald A. M. Buijsen, Linda M. van der Graaf, Elsa C. Kuijper, Barry A. Pepers, Elena Daoutsali, Lotte Weel, Vered Raz, David A. Parfitt and Willeke M. C. van Roon-Mom
Biomedicines 2024, 12(9), 1933; https://doi.org/10.3390/biomedicines12091933 - 23 Aug 2024
Viewed by 1529
Abstract
Antisense technology demonstrates significant potential for addressing inherited brain diseases, with over a dozen products already available and numerous others in the development pipeline. The versatility of differentiating induced pluripotent stem cells (iPSCs) into nearly all neural cell types proves invaluable for comprehending [...] Read more.
Antisense technology demonstrates significant potential for addressing inherited brain diseases, with over a dozen products already available and numerous others in the development pipeline. The versatility of differentiating induced pluripotent stem cells (iPSCs) into nearly all neural cell types proves invaluable for comprehending the mechanisms behind neurological diseases, replicating cellular phenotypes, and advancing the testing and development of new therapies, including antisense oligonucleotide therapeutics. While delivering antisense oligonucleotides (ASOs) to human iPSC-based neuronal models has posed challenges, this study explores various delivery methods, including lipid-based transfection, gymnotic uptake, Ca(2+)-enhanced medium (CEM)-based delivery, and electroporation, in 2D and 3D hiPSC-derived neuronal models. This study reveals that CEM-based delivery exhibits efficiency and low toxicity in both 2D neuronal cultures and 3D brain organoids. Furthermore, the findings indicate that CEM is slightly more effective in neurons than in astrocytes, suggesting promising avenues for further exploration and optimization of preclinical ASO strategies in the treatment of neurological disorders. Full article
(This article belongs to the Special Issue Applications of 3D Cell Culture in Biomedicines)
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24 pages, 7518 KiB  
Article
Three-Dimensional Hepatocyte Spheroids: Model for Assessing Chemotherapy in Hepatocellular Carcinoma
by Felix Royo, Clara Garcia-Vallicrosa, Maria Azparren-Angulo, Guillermo Bordanaba-Florit, Silvia Lopez-Sarrio and Juan Manuel Falcon-Perez
Biomedicines 2024, 12(6), 1200; https://doi.org/10.3390/biomedicines12061200 - 28 May 2024
Viewed by 1666
Abstract
Background: Three-dimensional cellular models provide a more comprehensive representation of in vivo cell properties, encompassing physiological characteristics and drug susceptibility. Methods: Primary hepatocytes were seeded in ultra-low attachment plates to form spheroids, with or without tumoral cells. Spheroid structure, cell proliferation, and apoptosis [...] Read more.
Background: Three-dimensional cellular models provide a more comprehensive representation of in vivo cell properties, encompassing physiological characteristics and drug susceptibility. Methods: Primary hepatocytes were seeded in ultra-low attachment plates to form spheroids, with or without tumoral cells. Spheroid structure, cell proliferation, and apoptosis were analyzed using histological staining techniques. In addition, extracellular vesicles were isolated from conditioned media by differential ultracentrifugation. Spheroids were exposed to cytotoxic drugs, and both spheroid growth and cell death were measured by microscopic imaging and flow cytometry with vital staining, respectively. Results: Concerning spheroid structure, an active outer layer forms a boundary with the media, while the inner core comprises a mass of cell debris. Hepatocyte-formed spheroids release vesicles into the extracellular media, and a decrease in the concentration of vesicles in the culture media can be observed over time. When co-cultured with tumoral cells, a distinct distribution pattern emerges over the primary hepatocytes, resulting in different spheroid conformations. Tumoral cell growth was compromised upon antitumoral drug challenges. Conclusions: Treatment of mixed spheroids with different cytotoxic drugs enables the characterization of drug effects on both hepatocytes and tumoral cells, determining drug specificity effects on these cell types. Full article
(This article belongs to the Special Issue Applications of 3D Cell Culture in Biomedicines)
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14 pages, 5975 KiB  
Article
A Platform for Testing the Biocompatibility of Implants: Silicone Induces a Proinflammatory Response in a 3D Skin Equivalent
by Rima Nuwayhid, Torsten Schulz, Frank Siemers, Jeannine Schreiter, Philipp Kobbe, Gunther Hofmann, Stefan Langer and Olga Kurow
Biomedicines 2024, 12(1), 224; https://doi.org/10.3390/biomedicines12010224 - 19 Jan 2024
Cited by 3 | Viewed by 1931
Abstract
Biocompatibility testing of materials is carried out in 2D cell cultures or animal models despite serious limitations. 3D skin equivalents are advanced in vitro models for human skin. Silicone has been shown to be noncytotoxic but capable of eliciting an immune response. Our [...] Read more.
Biocompatibility testing of materials is carried out in 2D cell cultures or animal models despite serious limitations. 3D skin equivalents are advanced in vitro models for human skin. Silicone has been shown to be noncytotoxic but capable of eliciting an immune response. Our aim was to (1) establish a 3D skin equivalent to (2) assess the proinflammatory properties of silicone. We developed a coculture of keratinocytes and fibroblasts resulting in a 3D skin equivalent with an implant using samples from a breast implant. Samples with and without the silicone implant were studied histologically and immunohistochemically in comparison to native human skin samples. Cytotoxicity was assessed via LDH-assay, and cytokine response was assessed via ELISA. Histologically, our 3D skin equivalents had a four-layered epidermal and a dermal component. The presence of tight junctions was demonstrated in immunofluorescence. The only difference in 3D skin equivalents with implants was an epidermal thinning. Implanting the silicone samples did not cause more cell death, however, an inflammatory cytokine response was triggered. We were able to establish an organotypical 3D skin equivalent with an implant, which can be utilised for studies on biocompatibility of materials. This first integration of silicone into a 3D skin equivalent confirmed previous findings on silicone being non-cell-toxic but capable of exerting a proinflammatory effect. Full article
(This article belongs to the Special Issue Applications of 3D Cell Culture in Biomedicines)
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