Yonghyo Kim, Myoung-Hee Kang, Geon‐Woo Kim, Yong-Hee Cho
{"title":"Small molecule-induced destabilization of β-catenin and RAS is the ideal strategies for suppressing colorectal cancer","authors":"Yonghyo Kim, Myoung-Hee Kang, Geon‐Woo Kim, Yong-Hee Cho","doi":"10.51335/organoid.2023.3.e4","DOIUrl":"https://doi.org/10.51335/organoid.2023.3.e4","url":null,"abstract":"Background: Mutations of adenomatous polyposis coli (APC) and KRAS play essential roles in the development of colorectal cancer (CRC) by forming an abnormal colon morphology. Despite intensive efforts to discover therapeutic strategies to re-transform cancer cells into normal cells, no effective approaches have been reported yet.Methods: In this study, we aimed to identify therapeutic strategies for inducing morphological changes of tumor organoids to structures similar to the normal intestine in ApcMin/+/KrasG12DLA2 mice by using KYA1797K, a dual inhibitor of the Wnt/β-catenin and RAS signaling pathways.Results: KYA1797K, previously identified as a dual inhibitor of the Wnt/β-catenin and RAS pathways, inhibited the growth of organoids derived from tumor cells of ApcMin/+/KrasG12DLA2 mice, with the transformation of benign tumor structures into normal structures, similar to bone morphogenetic protein 4 (BMP4), an intestinal differentiation signaling inducer.Conclusion: Given the anti-cancer effects of KYA1797K and its ability to induce morphological changes similar to those elicited by BMP4 treatment, the dual suppression of Wnt/β-catenin and RAS signaling is a potential therapy for treating CRC.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78875157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seonghyuk Park, Youngtaek Kim, Jihoon Ko, Jiyoung Song, Jeeyun Lee, Young-Kwon Hong, N. Jeon
{"title":"One-step achievement of tumor spheroid-induced angiogenesis in a high-throughput microfluidic platform: one-step tumor angiogenesis platform","authors":"Seonghyuk Park, Youngtaek Kim, Jihoon Ko, Jiyoung Song, Jeeyun Lee, Young-Kwon Hong, N. Jeon","doi":"10.51335/organoid.2023.3.e3","DOIUrl":"https://doi.org/10.51335/organoid.2023.3.e3","url":null,"abstract":"Research on the development of anti-cancer drugs has progressed, but the low reliability of animal experiments due to biological differences between animals and humans causes failures in the clinical process. To overcome this limitation, 3-dimensional (3D) in vitro models have been developed to mimic the human cellular microenvironment using polydimethylsiloxane (PDMS). However, due to the characteristics and limitations of PDMS, it has low efficiency and is not suitable to be applied in the preclinical testing of a drug. High-throughput microfluidic platforms fabricated by injection molding have been developed, but these platforms require a laborious process when handling spheroids. We recently developed an injection-molded plastic array 3D culture tissue platform that integrates the process from spheroid formation to reconstruction of an in vitro model with spheroids (All-in-One-IMPACT). In this study, we implemented a 3D tumor spheroid angiogenesis model in the developed platform. We analyzed the tendency for angiogenesis according to gel concentration and confirmed that angiogenesis occurred using cancer cell lines and patient-derived cancer cells (PDCs). We also administered an anti-cancer drug to the PDC tumor spheroid angiogenesis model to observe the drug’s effect on angiogenesis according to its concentration. We demonstrated that our platform can be used to study the tumor microenvironment (TME) and drug screening. We expect that this platform will contribute to further research on the complex mechanisms of the TME and predictive preclinical models.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79221225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Suhan Lee, H. Park, Sang‐Keun Sung, Ju Kyung Lee, H. Kim
{"title":"A polymer-based artificial microenvironment for enhancing cell adhesion","authors":"Suhan Lee, H. Park, Sang‐Keun Sung, Ju Kyung Lee, H. Kim","doi":"10.51335/organoid.2023.3.e8","DOIUrl":"https://doi.org/10.51335/organoid.2023.3.e8","url":null,"abstract":"An efficient platform capable of cell adhesion needs to be developed to understand cell activities such as cell differentiation, diffusion, and migration. The basic sequence of cell adhesion involves cells communicating with their environment by generating mechanical and chemical signals. Thin polymeric films with micro- or nano-patterns are widely used to support cell growth with conformal contact at the biointerface. However, stable and biocompatible films with high reproducibility on a flexible substrate remain a challenge. As described here, we developed micro-pattern poly(tetrafluoroethyleneco-perfluoro-3,6-dioxa-4-methyl-7-octenesulfonic acid) (Nafion) films fabricated by a molding process. We present the fabrication and characterization of flexible, micro-patterned Nafion films and the evaluation of cell adhesion and alignment on these films. We found that cell adhesion and migration/direction could be modulated by controlling the surface architecture. This approach offers a new platform that constitutes a promising tool for use in flexible cell-based platforms and devices to observe cell-cell and cell-surface interactions.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"255 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79500996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Engineered adipose tissue platforms: recent breakthroughs and future perspectives","authors":"Heejeong Yoon, Tae-Eun Park","doi":"10.51335/organoid.2023.3.e1","DOIUrl":"https://doi.org/10.51335/organoid.2023.3.e1","url":null,"abstract":"As overweight and obesity rates have increased worldwide, the prevalence of metabolic disorders has also grown. Due to the lack of physiologically relevant adipose tissue platforms, research in adipose tissue biology has relied on animal models, leading to false conclusions on pathophysiological mechanisms and therapeutic efficacy. Despite the urgent need for an adipose tissue model, it is still extremely difficult to cultivate mature adipocytes and recapitulate multi-cellular interactions in adipose tissue in vitro. For this reason, adipose tissue modeling requires new technologies that allow better culture conditions for adipocytes and contain a complex network of microenvironments. Herein, we discuss recent technologies, including 3-dimensional (3D) adipocyte spheroids, biomaterial-based 3D culture, 3D bioprinting, and microphysiological systems, which may offer new opportunities to discover drugs targeting adipose tissue.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89446821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Induced pluripotent stem cell-derived hematopoietic stem and progenitor cells: potential, challenges, and future perspectives","authors":"Myoung Hee Han, Da-Hyun Kim, Kyung-Rok Yu","doi":"10.51335/organoid.2023.3.e2","DOIUrl":"https://doi.org/10.51335/organoid.2023.3.e2","url":null,"abstract":"Hematopoietic stem and progenitor cells (HSPCs) are responsible for the lifetime dynamics of hematopoiesis, as they are well known for their self-renewing ability and multipotency to differentiate into all types of blood cells, including both myeloid and lymphoid lineages. However, due to their limited amount and accessibility, there is a strong need to search out alternative methods to produce HSPCs. In this review, we suggest induced pluripotent stem cells (iPSCs) as a new viable source for HSPC production because these cells have the potential to self-renew while being relatively easy to modify. Recent studies have revealed that the recapitulation of definitive hematopoiesis is the key to the successful in vitro production of HSPCs with multilineage potential. Therefore, we summarized recent progress in establishing the generation of definitive HSPCs with high maturity and functionality in vitro. Definitive HSPCs can be used in disease modeling and gene therapy for genetic blood disorders via gene modification in iPSCs, applied in cellular immunotherapy in the form of a universal chimeric antigen receptor system, and may recapitulate the intricate immune system within the iPSC-derived organoids that closely mimic the in vivo pathophysiological environment. In summary, this review provides an overview of the generation of HSPCs from iPSCs, in terms of the developmental process of hematopoiesis, in vitro attempts to produce iPSC-derived definitive HSPCs, and the following applications of these cells in numerous areas. This review sheds light on the concept of iPSC-derived definitive HSPCs, setting a milestone for artificial blood production in the near future.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75464493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyeong Jun Cho, Jeong Uk Lim, S. Kim, Y. Hwang, Jong Y. Park, Dong Woo Lee, C. Yeo
{"title":"Rapid anticancer drug screening using patient-derived lung cancer organoids: a case report","authors":"Hyeong Jun Cho, Jeong Uk Lim, S. Kim, Y. Hwang, Jong Y. Park, Dong Woo Lee, C. Yeo","doi":"10.51335/organoid.2022.2.e10","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e10","url":null,"abstract":"A variety of anticancer drugs and targeted agents for lung cancer have been developed, but some patients do not respond to these medications as intended. Therefore, there is an urgent need to develop a tool for predicting the anticancer drug response of each patient. Patient-derived tumor organoids (PDOs) have emerged as reliable in vitro tools for developing precision medicine. Herein, we describe a case of a 50-year-old nonsmoking man who was diagnosed with non-small cell lung cancer. Initially, no clinical symptoms were found in this patient. Postoperative pathology confirmed a stage Ib tumor, and an epidermal growth factor receptor (EGFR) mutation (exon21p.L858R) was detected in the patient’s lung tumor specimen. The patient later showed intracranial relapse 17 months after complete resection. An organoid culture was established from the resected brain metastatic tissue and a drug sensitivity test showed, within 72 hours, that the organoids were resistant to gefitinib and osimertinib. Our results recapitulated the patient’s response to anticancer drugs, demonstrating the potential of PDOs for precision medicine.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91251125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gastric stem cell research and gastric organoids","authors":"Haengdueng Jeong, K. Nam","doi":"10.51335/organoid.2022.2.e27","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e27","url":null,"abstract":"The stomach is a complex organ lined with ordered epithelium consisting of different adult stem cell (ASC) pools. In the previous decade, research into gastric epithelial stem cells has been performed using lineage tracing methods, and several putative ASC markers in the gastric gland have been identified, although their roles in homeostasis maintenance and the origin of cancer remain to be clarified. With advances in gastric stem cell research, 3-dimensional (3D) organoid culture has been developed on the basis of in-depth insights into the control of stem cell self-renewal, proliferation, and differentiation. Since the initial report that single intestinal stem cells have the ability to generate long-lived 3D structures that exhibit budding forms and self-renewal, tissue-specific adaptations of this method have been established in various organs, such as the small intestine, colon, liver, and stomach. In the murine stomach, putative ASCs isolated from the corpus and antrum generate gastric organoids that can simulate organ-specific cells to some extent. In addition, a few trials have been conducted to generate long-lived 3D organoids using human-derived ASCs and pluripotent stem cells. We hope that this review will provide comprehensive knowledge on gastric stem cell research and gastric organoids.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73870305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Stress granule formation as a marker of cellular toxicity in lung organoids","authors":"Seung-Yeon Kim, Kee K. Kim, Eun-Mi Kim","doi":"10.51335/organoid.2022.2.e28","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e28","url":null,"abstract":"Cells regulate protein synthesis under stressful circumstances by forming cytoplasmic RNA granules, termed stress granules (SGs). SGs are membrane-less organelles that function as a protective mechanism in response to stress. They function through liquid-liquid phase separation, which is a vital process comprising 2 distinct de-mixed liquid phases. The components of SGs, such as G3BP1, can serve as biomarkers of cell toxicity. Respiratory diseases are among the leading causes of death globally. After the humidifier disinfectant disaster in Korea in 2011, social concerns over respiratory disease-related deaths have been raised, and the importance of inhalation toxicity testing has been emphasized. Traditionally, in vivo animal models have been used to assess inhalation toxicity, but these models still have limitations owing to physiological differences between species. To overcome these limitations, human immortalized lung epithelial and lung cancer cell lines have been used to evaluate lung toxicity in vitro. Human stem cell-derived 3-dimensional organoid technology has recently been developed in various research fields, including lung toxicity. This review discusses SG-related proteins as potential biomarkers for lung toxicity assessment, especially in human lung organoids under stress conditions, such as exposure to toxic chemicals.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90490692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jooyeon Lee, Hyosin Baek, Seok-Ho Hong, Jong-Hee Lee, Seung-jun Wang, Ji Young Lee, Myung Ha Song, Se-Ran Yang
{"title":"Alveolar organoids: development of an in vitro assay to facilitate pulmonary toxicity assessments","authors":"Jooyeon Lee, Hyosin Baek, Seok-Ho Hong, Jong-Hee Lee, Seung-jun Wang, Ji Young Lee, Myung Ha Song, Se-Ran Yang","doi":"10.51335/organoid.2022.2.e31","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e31","url":null,"abstract":"Animal experiments have been performed to predict toxicity in humans in many fields, including toxicology, medicine, and pharmacology, and have contributed to increasing life expectancy. However, animal testing has been a controversial issue for over 100 years due to ethical concerns, and inter-species differences pose limitations for understanding human responses to toxicity. In recent years, many researchers have developed in vitro and in silico alternatives to using animals (e.g., 3-dimensional [3D] organoid culture, organs-on-a-chip, and advanced computer modeling). In this study, we generated 3D alveolar organoids (AOs) for pulmonary toxicity testing following exposure to chemicals, instead of animal models or two-dimensional culture of a single cell type. After human induced pluripotent stem cells were cultured with differentiation medium corresponding to each step for 14 days in 6-well plates, AOs were generated by forced aggregation and cultured with differentiation medium. The AOs were exposed to acrolein and sodium chromate for 24, 72, and 120 hours, and we determined the cytotoxicity of these chemicals using the MTT assay. Exposure to acrolein and sodium chromate for 24 hours decreased proliferation, but the organoid size did not change considerably. However, long-term exposure to acrolein and sodium chromate significantly decreased the organoid size. These findings suggest that AOs could facilitate acute toxicity assessments based on measurements of cell viability in AOs, as well as sub-chronic toxicity assessments based on measurements of both size and viability.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82503287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Generation of proximal tubule spheroids for nephrotoxicity assessment","authors":"D. Kim, J. Lim, Cho-Rok Jung, H. Kang","doi":"10.51335/organoid.2022.2.e30","DOIUrl":"https://doi.org/10.51335/organoid.2022.2.e30","url":null,"abstract":"To date, nephrotoxicity in new drug development has been evaluated through two-dimensional culture of representative cell lines, such as HK-2 and human proximal tubule epithelial cells (hPTECs). Approximately 20% of new drugs that were safe in preclinical studies were withdrawn from clinical trials due to nephrotoxicity, which means the current renal cell lines used in preclinical trials have limitations for the accurate detection of nephrotoxicity. Here, we established proximal tubule cell lines from immortalized mixed primary renal cells and generated functional proximal tubule cell spheroids, which expressed all apical basolateral transporters and showed epithelial polarity. Moreover, they showed a more sensitive drug response than hPTECs, which have been commonly used as in vitro kidney models. Taken together, the proximal tubule cells described in this study provide a more stable, reproducible, and accurate in vitro kidney model for predicting nephrotoxicity, which could help early compound development.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87201614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}