Generation of brain organoids from mouse ESCs via teratoma formation

Lee, Won Ji; Lee, Jeong Eon; Hong, Yean Ju; Yoon, Sang Hoon; Song, Hyuk; Park, Chankyu; Hong, Kwonho; Choi, Youngsok; Tae, Jeong

doi:10.1016/j.scr.2020.102100

Cited by 3 publications

(14 citation statements)

References 22 publications

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“…Researchers indicated that, as teratomas could generate a wide array of cell types and grow to a large size because of their vascularization, they could be used as a model for multilineage human development (McDonald et al, 2020). In view of the rapid technical development in this field, we believe that teratomas are in a time of extraordinary opportunity to better generate organoids (Suzuki et al, 2013;Lee et al, 2020;McDonald et al, 2020).…”

Section: Other Limitationsmentioning

confidence: 99%

“…For instance, through miRNA-based molecular sculpting, teratomas could be engineered toward a desired lineage to apply for studying developmental biology and human disease (McDonald et al, 2020). Moreover, desired cell types could be enriched in teratomas by genetic engineering to investigate tissues of our interest (Suzuki et al, 2013;Lee et al, 2020). Another limitation of teratomas is their complicated somatic tissues arranged in a semirandom manner.…”

Section: Limitations Of Current Teratomasmentioning

confidence: 99%

“…Teratomas provide a microenvironment that is more suitable for stem cell growth. The teratoma system facilitates the formation of embryoid-body-like aggregates from stem cells with poor ability to differentiate and could also be used to enrich specific cell lineages (Lee et al, 2020). Moreover, teratomas spontaneously develop blood vessels with a short duration of neoplasia, which could promote vascularization and shorten the cultivation time of organoids (Stachelscheid et al, 2013;Lee et al, 2020;McDonald et al, 2020).…”

Section: Lessons Form Teraomtas To Better Generate Organoidsmentioning

confidence: 99%

“…The formation of embryoid-body-like aggregates is the first step in organoid formation. However, partially reprogrammed iPSCs sometimes fail to differentiate in vitro, resulting in the inability of an embryoid-body-like aggregate to form (Lee et al, 2020), possibly because the isolated iPSCs retain some somatic memory, at least at low passages (Kim et al, 2011;Ohi et al, 2011). The other reason for the failure of an embryoid-body-like aggregate to form is that the established iPSC lines may contain aberrant traits, which may be caused by the stoichiometry of reprogramming factors and culture conditions (Newman and Cooper, 2010;Carey et al, 2011).…”

Section: Inducing the Formation Of Embryoid-body-like Aggregatesmentioning

confidence: 99%

“…Recently, several studies showed that single specific lineage cell types, such as skeletal muscle stem cells, neural stem cells, and hematopoietic stem cells, have already been enriched from mouse PSCs through teratoma formation (Chan et al, 2018;Philipp et al, 2018;Kim et al, 2019). These enriched cells could be cultured in vitro, and even specific vascularized tissues could be isolated to generate organoids (Lee et al, 2020). Moreover, the variations of cell types in teratomas could be an advantage to generate complex tissues, which provides a possibility to investigate human development at a multi-organ level.…”

Section: Introductionmentioning

confidence: 99%

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To Better Generate Organoids, What Can We Learn From Teratomas?

Gao

et al. 2021

Front. Cell Dev. Biol.

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The genomic profile of animal models is not completely matched with the genomic profile of humans, and 2D cultures do not represent the cellular heterogeneity and tissue architecture found in tissues of their origin. Derived from 3D culture systems, organoids establish a crucial bridge between 2D cell cultures and in vivo animal models. Organoids have wide and promising applications in developmental research, disease modeling, drug screening, precision therapy, and regenerative medicine. However, current organoids represent only single or partial components of a tissue, which lack blood vessels, native microenvironment, communication with near tissues, and a continuous dorsal-ventral axis within 3D culture systems. Although efforts have been made to solve these problems, unfortunately, there is no ideal method. Teratoma, which has been frequently studied in pathological conditions, was recently discovered as a new in vivo model for developmental studies. In contrast to organoids, teratomas have vascularized 3D structures and regions of complex tissue-like organization. Studies have demonstrated that teratomas can be used to mimic multilineage human development, enrich specific somatic progenitor/stem cells, and even generate brain organoids. These results provide unique opportunities to promote our understanding of the vascularization and maturation of organoids. In this review, we first summarize the basic characteristics, applications, and limitations of both organoids and teratomas and further discuss the possibility that in vivo teratoma systems can be used to promote the vascularization and maturation of organoids within an in vitro 3D culture system.

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Section: Other Limitationsmentioning

confidence: 99%

Section: Limitations Of Current Teratomasmentioning

confidence: 99%

Section: Lessons Form Teraomtas To Better Generate Organoidsmentioning

confidence: 99%

Section: Inducing the Formation Of Embryoid-body-like Aggregatesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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To Better Generate Organoids, What Can We Learn From Teratomas?

Gao

et al. 2021

Front. Cell Dev. Biol.

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Pluripotent stem cells: Basic biology or else differentiations aimed at translational research and the role of flow cytometry

Bose

Nihad

2023

Cytometry Pt A

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Pluripotent stem cell research has revolutionized the modern era for the past 14 years with the advent of induced pluripotent stem cells. Before this time, scientists had access to human and mouse embryonic stem cells primarily for basic research and an attempt towards lineage-specific differentiations for cell therapy applications. Regarding pluripotent stem cells, expression of bonafide marker proteins such as Oct4, Nanog, Sox2, Klf4, c-Myc, and Lin28 have been considered giving a perfect readout for pluripotent stem cells and assessed using an analytical flow cytometer. In addition to the intracellular markers, surface markers such as stagespecific embryonic antigen-1 for mouse cells and SSEA-4 for human cells are needed to sort pure populations of stem cells for further downstream applications for cell therapy. The surface marker SSEA-4 is the most appropriate for obtaining pure populations of human pluripotent stem cells. When differentiated in a controlled manner using growth factors or small molecules, it is mandatory to assess the downregulation of pluripotency markers (Oct4, Nanog, Sox2, and Klf4) with subsequent up-regulation of stage-specific differentiation markers. Such assessments are done using flow cytometry. Pluripotent stem cells have a high teratoma-forming potential in vivo. Small amounts of undifferentiated PSCs might lead to dangerous teratomas upon transplantation if leftover in the pool of differentiated cells. Hence, flow cytometry is essential for sorting out PSC populations with teratoma-forming potential. The pure populations of differentiated progenitors need to be flow-sorted before differentiating them further for cell therapy applications. For example, Glycoprotein 2 is a specific cell-surface marker for pancreatic progenitors that enables one to sort the pancreatic progenitors differentiated from human PSCs. Taken together, analytical flow cytometry, and cell sorting provide indispensable tools in PSC research and cell therapy.

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Advancement of Organoid Technology in Regenerative Medicine

Arjmand

Rabbani

Soveyzi

et al. 2022

Regen. Eng. Transl. Med.

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Purpose Organoids are three-dimensional cultures of stem cells in an environment similar to the body’s extracellular matrix. This is also a novel development in the realm of regenerative medicine. Stem cells can begin to develop into 3D structures by modifying signaling pathways. To form organoids, stem cells are transplanted into the extracellular matrix. Organoids have provided the required technologies to reproduce human tissues. As a result, it might be used in place of animal models in scientific study. The key goals of these investigations are research into viral and genetic illnesses, malignancies, and extracellular vesicles, pharmaceutical discovery, and organ transplantation. Organoids can help pave the road for precision medicine through genetic editing, pharmaceutical development, and cell therapy. Methods PubMed, Google Scholar, and Scopus were used to search for all relevant papers written in English (1907–2021). The study abstracts were scrutinized. Studies on the use of stem-cell-derived organoids in regenerative medicine, organoids as 3D culture models for EVs analysis, and organoids for precision medicine were included. Articles with other irrelevant aims, meetings, letters, commentaries, congress and conference abstracts, and articles with no available full texts were excluded. Results According to the included studies, organoids have various origins, types, and applications in regenerative and precision medicine, as well as an important role in studying extracellular vesicles. Conclusion Organoids are considered a bridge that connects preclinical studies to clinical ones. However, the lack of a standardized protocol and other barriers addressed in this review, hinder the vast use of this technology. Lay Summary Organoids are 3D stem cell propagations in biological or synthetic scaffolds that mimic ECM to allow intercellular or matrix-cellular crosstalk. Because these structures are similar to organs in the body, they can be used as research models. Organoids are medicine’s future hope for organ transplantation, tumor biobank formation, and the development of precision medicine. Organoid models can be used to study cell-to-cell interactions as well as effective factors like inflammation and aging. Bioengineering technologies are also used to define the size, shape, and composition of organoids before transforming them into precise structures. Finally, the importance of organoid applications in regenerative medicine has opened a new window for a better understanding of biological research, as discussed in this study.

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Generation of brain organoids from mouse ESCs via teratoma formation

Cited by 3 publications

References 22 publications

To Better Generate Organoids, What Can We Learn From Teratomas?

To Better Generate Organoids, What Can We Learn From Teratomas?

Pluripotent stem cells: Basic biology or else differentiations aimed at translational research and the role of flow cytometry

Advancement of Organoid Technology in Regenerative Medicine

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