{"title":"Kidney organoids: development and applications","authors":"Hye-Youn Kim, Seyoung Yu, Yo Jun Choi, H. Gee","doi":"10.51335/organoid.2023.3.e10","DOIUrl":"https://doi.org/10.51335/organoid.2023.3.e10","url":null,"abstract":"Since the first publication on generating kidney-like cell aggregates from pluripotent stem cells, various modifications have been made to develop more complex and detailed kidney structures. In contrast to earlier models that featured nephron-like structures, these advances have improved the differentiation efficiency and similarity to the human kidney. Presently, kidney organoids contain not only nephrons and ureteric buds but also stromal cells. These organoids mimic the structural similarities and developmental processes of the kidneys, while reflecting their physiological properties. Kidney tubuloids derived from adult stem cells offer the advantage of long-term culture and expansion, but they include only tubular structures and lack glomerular components. In this review, we discuss the induction protocols for kidney organoids and tubuloids, as well as their potential applications in understanding kidney development, renal pathogenesis, and drug screening.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"98 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79258176","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":"Suspension-cultured taste bud organoids recapitulate in vivo taste buds","authors":"Anish Ashok Adpaikar, Jong‐Min Lee, Han-Sung Jung","doi":"10.51335/organoid.2023.3.e9","DOIUrl":"https://doi.org/10.51335/organoid.2023.3.e9","url":null,"abstract":"Background: Taste buds are a complex organ and require a plethora of growth factors for their development, homeostasis, and regeneration. Taste bud organoids provide a platform for understanding their development, disease and regeneration.Methods: In this study, we focused on identifying the localization of receptors involved during taste bud development in taste bud organoids, either in an extracellular matrix scaffold (Matrigel) or in the absence of a scaffold with suspension culture.Results: Compared to Matrigel-cultured organoids, suspension organoids showed stable expression of nerve growth factor receptor (NGFR) cells, which are important for innervation. Transporters for glucose metabolism, such as GLUT1, GLUT2, and the insulin receptor (IGF1R), were observed in suspension-cultured organoids. Furthermore, immunostaining for downstream phosphorylated signaling molecules indicated that the NGFR and IGFR pathways were functional and active in the organoids.Conclusion: Based on these results, suspension-cultured organoids may provide an efficient model for mimicking in vivo taste buds compared to conventional Matrigel organoids.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"112 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90670115","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}
S. Park, Harshita Sharma, W. Kim, Yonghyun Gwon, H. Kim, Y. Choung, Jangho Kim
{"title":"Microengineered organoids: reconstituting organ-level functions in vitro","authors":"S. Park, Harshita Sharma, W. Kim, Yonghyun Gwon, H. Kim, Y. Choung, Jangho Kim","doi":"10.51335/organoid.2023.3.e5","DOIUrl":"https://doi.org/10.51335/organoid.2023.3.e5","url":null,"abstract":"In vitro miniaturized organoids are innovative tools with varying applications in biomedical engineering, such as drug testing, disease modeling, organ development studies, and regenerative medicine. However, conventional organoid development has several hurdles in reproducing and reconstituting organ-level functions in vitro, hampering advanced and impactful studies. In this review, we summarize the emerging microengineering-based organoid development techniques aiming to overcome these hurdles. First, we provide basic information on microengineering techniques, including those for reconstituting organoids with organ-level functions. We then focus on recent advances in microengineered organoids with better morphological, physiological, and functional characteristics than conventionally developed organoids. We believe that microengineered organoids possessing organ-level functions in vitro will enable widespread studies in the field of biological sciences and have clinical applications.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"245 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80578741","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}
Hantai Kim, Young Sun Kim, Y. Kim, Jungho Ha, Siung Sung, J. Jang, S. Park, Jangho Kim, Kyungeun Kim, Y. Choung
{"title":"Development of otic organoids and their current status","authors":"Hantai Kim, Young Sun Kim, Y. Kim, Jungho Ha, Siung Sung, J. Jang, S. Park, Jangho Kim, Kyungeun Kim, Y. Choung","doi":"10.51335/organoid.2023.3.e7","DOIUrl":"https://doi.org/10.51335/organoid.2023.3.e7","url":null,"abstract":"The inner ear is responsible for both hearing and balance in the body, and since the initial development of otic (inner ear) organoids from mouse pluripotent stem cells (PSCs) in 2013, significant advances have been made in this field. Bone morphogenetic proteins, fibroblast growth factors, and Wnt agonists, which are signaling molecules in the early development of the inner ear, can induce PSCs into the otic fate. In the inner ear, hair cells and the surrounding supporting cells are essential for proper function and structure. Recent advancements in otic organoid research have enabled the generation of cells that closely resemble these key components. The developed otic organoids contain both hair cell-like cells and supporting cells, which have been confirmed to have the intrinsic function of those cell types. Otic organoids have been used for disease modeling and are expected to be more widely applied in various areas of research on the inner ear. However, the otic organoids developed to date remain immature. Although they mimic hair cells, their properties resemble vestibular (balance) hair cells more closely than cochlear (auditory) hair cells. The ultimate goal of research on the inner ear is hearing restoration and prevention; thus, it is essential to produce otic organoids that contain cochlear hair cells. In addition, the organ of Corti—a cell arrangement unique to the cochlea—has not yet been simulated. Along with a description of the current status of otic organoids, this review article will discuss future directions for otic organoids in inner ear research.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82060700","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}
Jiyoung Song, Jihoon Ko, Nakwon Choi, N. Jeon, Hongnam Kim
{"title":"Tumor spheroid-based and microtumor-based vascularized models for replicating the vascularized tumor microenvironment","authors":"Jiyoung Song, Jihoon Ko, Nakwon Choi, N. Jeon, Hongnam Kim","doi":"10.51335/organoid.2023.3.e6","DOIUrl":"https://doi.org/10.51335/organoid.2023.3.e6","url":null,"abstract":"BackgroundTumor vasculature is a crucial pathway for supplying nutrients and oxygen to tumors during their progression, as well as facilitating the delivery of anticancer drugs or immunotherapeutic agents. Microfluidic technology has emerged as a powerful tool in creating microenvironments within 3D cell cultures that more closely resemble in vivo conditions, by enabling precise control of fluid flow. As a result, microfluidic devices have made significant progress in replicating both the structural and functional characteristics of the tumor microenvironment in vitro. Methods and ResultsIn this study, we present two approaches for reconstructing the tumor vasculature using tumor spheroids or microtumors, with a particular focus on in vivo functional mimicry and experimental reproducibility. Tumor spheroid-based vascular models provide an observatory window into tumor vasculature centered on tumor spheroids, enabling quantitative measurement of the degree of abnormality of blood vessels developing around the tumor spheroid and the invasiveness of metastatic tumors. Microtumor-based vascular models, on the other hand, have the potential to enhance our comprehension of advanced and metastatic cancers at the single-cell level by elucidating the proliferative and metastatic capacities of tumor cells, as well as the vascular permeability that is contingent upon the subtypes of tumor cells. ConclusionOur platforms provide valuable insights into the development of novel in vitro models for studying the tumor microenvironment and advancing our understanding of cancer biology.","PeriodicalId":100198,"journal":{"name":"Brain Organoid and Systems Neuroscience Journal","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75892018","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}
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}