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Article ; Online: Progresses in overcoming the limitations of in vitro erythropoiesis using human induced pluripotent stem cells.

Ju, Hyeonwoo / Sohn, Yeowon / Nam, Yoojun / Rim, Yeri Alice

2024 Volume 15, Issue 1, Page(s) 142

Abstract: Researchers have attempted to generate transfusable oxygen carriers to mitigate RBC supply shortages. In vitro generation of RBCs using stem cells such as hematopoietic stem and progenitor cells (HSPCs), embryonic stem cells (ESCs), and induced ... ...

Abstract	Researchers have attempted to generate transfusable oxygen carriers to mitigate RBC supply shortages. In vitro generation of RBCs using stem cells such as hematopoietic stem and progenitor cells (HSPCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs) has shown promise. Specifically, the limited supplies of HSPCs and ethical issues with ESCs make iPSCs the most promising candidate for in vitro RBC generation. However, researchers have encountered some major challenges when using iPSCs to produce transfusable RBC products, such as enucleation and RBC maturation. In addition, it has proven difficult to manufacture these products on a large scale. In this review, we provide a brief overview of erythropoiesis and examine endeavors to recapitulate erythropoiesis in vitro using various cell sources. Furthermore, we explore the current obstacles and potential solutions aimed at enabling the large-scale production of transfusable RBCs in vitro.
MeSH term(s)	Humans ; Erythropoiesis ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/metabolism ; Erythrocytes/cytology ; Erythrocytes/metabolism ; Cell Differentiation ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/metabolism
Language	English
Publishing date	2024-05-15
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-024-03754-9
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Article ; Online: Replacing Animal Testing with Stem Cell-Organoids : Advantages and Limitations.

Park, Guiyoung / Rim, Yeri Alice / Sohn, Yeowon / Nam, Yoojun / Ju, Ji Hyeon

Stem cell reviews and reports

2024

Abstract: Various groups including animal protection organizations, medical organizations, research centers, and even federal agencies such as the U.S. Food and Drug Administration, are working to minimize animal use in scientific experiments. This movement ... ...

Abstract	Various groups including animal protection organizations, medical organizations, research centers, and even federal agencies such as the U.S. Food and Drug Administration, are working to minimize animal use in scientific experiments. This movement primarily stems from animal welfare and ethical concerns. However, recent advances in technology and new studies in medicine have contributed to an increase in animal experiments throughout the years. With the rapid increase in animal testing, concerns arise including ethical issues, high cost, complex procedures, and potential inaccuracies.Alternative solutions have recently been investigated to address the problems of animal testing. Some of these technologies are related to stem cell technologies, such as organ-on-a-chip, organoids, and induced pluripotent stem cell models. The aim of the review is to focus on stem cell related methodologies, such as organoids, that can serve as an alternative to animal testing and discuss its advantages and limitations, alongside regulatory considerations.Although stem cell related methodologies has shortcomings, it has potential to replace animal testing. Achieving this requires further research on stem cells, with potential societal and technological benefits.
Language	English
Publishing date	2024-04-19
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2495577-2
ISSN	2629-3277 ; 1558-6804 ; 1550-8943
ISSN (online)	2629-3277 ; 1558-6804
ISSN	1550-8943
DOI	10.1007/s12015-024-10723-5
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Article ; Online: Anti-fibrotic effect of a selective estrogen receptor modulator in systemic sclerosis.

Kim, Yena / Nam, Yoojun / Rim, Yeri Alice / Ju, Ji Hyeon

Stem cell research & therapy

2022 Volume 13, Issue 1, Page(s) 303

Abstract: Background: The rarity of systemic sclerosis (SSc) has hampered the development of therapies for this intractable autoimmune disease. Induced pluripotent stem cell (iPSC) can be differentiated into the key disease-affected cells in vitro. The generation ...

Abstract	Background: The rarity of systemic sclerosis (SSc) has hampered the development of therapies for this intractable autoimmune disease. Induced pluripotent stem cell (iPSC) can be differentiated into the key disease-affected cells in vitro. The generation of patient-derived iPSCs has opened up possibilities for rare disease modeling. Since these cells can recapitulate the disease phenotypes of the cell in question, they are useful high-throughput platforms for screening for drugs that can reverse these abnormal phenotypes. Methods: SSc iPSC was generated from PBMC by Sendai virus. Human iPSC lines from SSc patients were differentiated into dermal fibroblasts and keratinocytes. The iPSC-derived differentiated cells from the SSc patients were used on high-throughput platforms to screen for FDA-approved drugs that could be effective treatments for SSc. Results: Skin organoids were generated from these cells exhibited fibrosis that resembled SSc skin. Screening of the 770-FDA-approved drug library showed that the anti-osteoporotic drug raloxifene reduced SSc iPSC-derived fibroblast proliferation and extracellular matrix production and skin fibrosis in organoids and bleomycin-induced SSc-model mice. Conclusions: This study reveals that a disease model of systemic sclerosis generated using iPSCs-derived skin organoid is a novel tool for in vitro and in vivo dermatologic research. Since raloxifene and bazedoxifene are well-tolerated anti-osteoporotic drugs, our findings suggest that selective estrogen receptor modulator (SERM)-class drugs could treat SSc fibrosis.
MeSH term(s)	Animals ; Cells, Cultured ; Fibroblasts/metabolism ; Fibrosis ; Humans ; Leukocytes, Mononuclear/metabolism ; Mice ; Raloxifene Hydrochloride/adverse effects ; Scleroderma, Systemic/genetics ; Selective Estrogen Receptor Modulators/adverse effects ; Skin/pathology ; Skin Diseases/pathology
Chemical Substances	Selective Estrogen Receptor Modulators ; Raloxifene Hydrochloride (4F86W47BR6)
Language	English
Publishing date	2022-07-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-022-02987-w
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Article ; Online: The Role of Chondrocyte Hypertrophy and Senescence in Osteoarthritis Initiation and Progression.

Rim, Yeri Alice / Nam, Yoojun / Ju, Ji Hyeon

International journal of molecular sciences

2020 Volume 21, Issue 7

Abstract: Osteoarthritis (OA) is the most common joint disease that causes pain and disability in the adult population. OA is primarily caused by trauma induced by an external force or by age-related cartilage damage. Chondrocyte hypertrophy or chondrocyte ... ...

Abstract	Osteoarthritis (OA) is the most common joint disease that causes pain and disability in the adult population. OA is primarily caused by trauma induced by an external force or by age-related cartilage damage. Chondrocyte hypertrophy or chondrocyte senescence is thought to play a role in the initiation and progression of OA. Although chondrocyte hypertrophy and cell death are both crucial steps during the natural process of endochondral bone formation, the abnormal activation of these two processes after injury or during aging seems to accelerate the progression of OA. However, the exact mechanisms of OA progression and these two processes remain poorly understood. Chondrocyte senescence and hypertrophy during OA share various markers and processes. In this study, we reviewed the changes that occur during chondrocyte hypertrophy or senescence in OA and the attempts that were made to regulate them. Regulation of hypertrophic or senescent chondrocytes might be a potential therapeutic target to slow down or stop OA progression; thus, a better understanding of the processes is required for management.
MeSH term(s)	Animals ; Biomarkers ; Cartilage, Articular/metabolism ; Cartilage, Articular/pathology ; Cell Differentiation ; Cell Proliferation ; Cellular Senescence ; Chondrocytes/metabolism ; Chondrocytes/pathology ; Chondrogenesis ; Disease Progression ; Disease Susceptibility ; Gene Expression Regulation ; Humans ; Hypertrophy ; Osteoarthritis/etiology ; Osteoarthritis/metabolism ; Osteoarthritis/pathology ; Osteoarthritis/therapy ; Osteogenesis ; Signal Transduction
Chemical Substances	Biomarkers
Language	English
Publishing date	2020-03-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21072358
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Article ; Online: Recent Developments in Clinical Applications of Mesenchymal Stem Cells in the Treatment of Rheumatoid Arthritis and Osteoarthritis.

Hwang, Joel Jihwan / Rim, Yeri Alice / Nam, Yoojun / Ju, Ji Hyeon

Frontiers in immunology

2021 Volume 12, Page(s) 631291

Abstract: Mesenchymal stem cell (MSC) therapies have been used as cell-based treatments for decades, owing to their anti-inflammatory, immunomodulatory, and regenerative properties. With high expectations, many ongoing clinical trials are investigating the safety ... ...

Abstract	Mesenchymal stem cell (MSC) therapies have been used as cell-based treatments for decades, owing to their anti-inflammatory, immunomodulatory, and regenerative properties. With high expectations, many ongoing clinical trials are investigating the safety and efficacy of MSC therapies to treat arthritic diseases. Studies on osteoarthritis (OA) have shown positive clinical outcomes, with improved joint function, pain level, and quality of life. In addition, few clinical MSC trials conducted on rheumatoid arthritis (RA) patients have also displayed some optimistic outlook. The largely positive outcomes in clinical trials without severe side effects establish MSCs as promising tools for arthritis treatment. However, further research is required to investigate its applicability in clinical settings. This review discusses the most recent advances in clinical studies on MSC therapies for OA and RA.
MeSH term(s)	Arthritis, Rheumatoid/therapy ; Cell- and Tissue-Based Therapy/methods ; Cell- and Tissue-Based Therapy/statistics & numerical data ; Cells, Cultured ; Clinical Trials as Topic ; Humans ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells ; Osteoarthritis/therapy ; Quality of Life
Language	English
Publishing date	2021-03-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.631291
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Article: Minicircles for Investigating and Treating Arthritic Diseases.

Rim, Yeri Alice / Nam, Yoojun / Park, Narae / Ju, Ji Hyeon

Pharmaceutics

2021 Volume 13, Issue 5

Abstract: Gene delivery systems have become an essential component of research and the development of therapeutics for various diseases. Minicircles are non-viral vectors with promising characteristics for application in a variety of fields. With their minimal ... ...

Abstract	Gene delivery systems have become an essential component of research and the development of therapeutics for various diseases. Minicircles are non-viral vectors with promising characteristics for application in a variety of fields. With their minimal size, minicircles exhibit relatively high safety and efficient delivery of genes of interest into cells. Cartilage tissue lacks the natural ability to heal, making it difficult to treat osteoarthritis (OA) and rheumatoid arthritis (RA), which are the two main types of joint-related disease. Although both OA and RA affect the joint, RA is an autoimmune disease, while OA is a degenerative joint condition. Gene transfer using minicircles has also been used in many studies regarding cartilage and its diseased conditions. In this review, we summarize the cartilage-, OA-, and RA-based studies that have used minicircles as the gene delivery system.
Language	English
Publishing date	2021-05-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics13050736
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Article ; Online: Review of the Current Trends in Clinical Trials Involving Induced Pluripotent Stem Cells.

Kim, Jennifer Yejean / Nam, Yoojun / Rim, Yeri Alice / Ju, Ji Hyeon

Stem cell reviews and reports

2021 Volume 18, Issue 1, Page(s) 142–154

Abstract: In 2006, the induced pluripotent stem cell (iPSC) was presented to the world, paving the way for the development of a magnitude of novel therapeutic alternatives, addressing a diverse range of diseases. However, despite the immense cell therapy potential, ...

Abstract	In 2006, the induced pluripotent stem cell (iPSC) was presented to the world, paving the way for the development of a magnitude of novel therapeutic alternatives, addressing a diverse range of diseases. However, despite the immense cell therapy potential, relatively few clinical trials evaluating iPSC-technology have actually translated into interventional, clinically applied treatment regimens. Herein, our aim was to determine trends in globally conducted clinical trials involving iPSCs. Data were derived both from well-known registries recording clinical trials from across the globe, and databases from individual countries. Comparisons were firstly drawn between observational and interventional studies before the latter was further analyzed in terms of therapeutic and nontherapeutic trials. Our main observations included global distribution, purpose, target size, and types of disorder relevant to evaluated trials. In terms of nontherapeutic trials, the USA conducted the majority, a large average number of participants-187-was included in the trials, and studies on circulatory system disorders comprised a slightly higher proportion of total studies. Conversely, Japan was the frontrunner in terms of conducting therapeutic trials, and the average number of participants was much lower, at roughly 29. Disorders of the circulatory, as well as nervous and visual systems, were all studied in equal measure. This review highlights the impact that iPSC-based cell therapies can have, should development thereof gain more traction. We lastly considered a few companies that are actively utilizing iPSCs in the development of therapies for various diseases, for whom the global trends in clinical trials could become increasingly important.
MeSH term(s)	Cell- and Tissue-Based Therapy ; Clinical Trials as Topic ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Japan
Language	English
Publishing date	2021-09-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2495577-2
ISSN	2629-3277 ; 1558-6804 ; 1550-8943
ISSN (online)	2629-3277 ; 1558-6804
ISSN	1550-8943
DOI	10.1007/s12015-021-10262-3
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Article ; Online: Prochondrogenic effect of decellularized extracellular matrix secreted from human induced pluripotent stem cell-derived chondrocytes.

Choi, Si Hwa / Lee, Kijun / Han, Heeju / Mo, Hyunkyung / Jung, Hyerin / Ryu, YoungWoo / Nam, Yoojun / Rim, Yeri Alice / Ju, Ji Hyeon

Acta biomaterialia

2023 Volume 167, Page(s) 234–248

Abstract: Cartilage is mainly composed of chondrocytes and the extracellular matrix (ECM), which transmits important biochemical and biomechanical signals necessary for differentiation and homeostasis. Human articular cartilage has a low ability for regeneration ... ...

Abstract	Cartilage is mainly composed of chondrocytes and the extracellular matrix (ECM), which transmits important biochemical and biomechanical signals necessary for differentiation and homeostasis. Human articular cartilage has a low ability for regeneration because it lacks blood vessels, nerves, and lymphatic vessels. Currently, cell therapeutics, including stem cells, provide a promising strategy for cartilage regeneration and treatment; however, there are various hurdles to overcome, such as immune rejection and teratoma formation. In this study, we assessed the applicability of stem cell-derived chondrocyte ECM for cartilage regeneration. Human induced pluripotent stem cell (hiPSC)-derived chondrocytes (iChondrocytes) were differentiated, and decellularized ECM (dECM) was successfully isolated from cultured chondrocytes. Isolated dECM enhanced the in vitro chondrogenesis of iPSCs when recellularized. Implanted dECM also restored osteochondral defects in a rat osteoarthritis model. A possible association with the glycogen synthase kinase-3 beta (GSK3β) pathway demonstrated the fate-determining importance of dECM in regulating cell differentiation. Collectively, we suggest the prochondrogenic effect of hiPSC-derived cartilage-like dECM and offer a promising approach of a noncellular therapeutic for articular cartilage reconstruction without cell transplantation. STATEMENT OF SIGNIFICANCE: Human articular cartilage has low ability for regeneration and cell culture-based therapeutics could aid cartilage regeneration. Yet, the applicability of human induced pluripotent stem cell-derived chondrocyte (iChondrocyte) extracellular matrix (ECM) has not been elucidated. Therefore, we first differentiated iChondrocytes and isolated the secreted ECM by decellularization. Recellularization was performed to confirm the pro-chondrogenic effect of the decellularized ECM (dECM). In addition, we confirmed the possibility of cartilage repair by transplanting the dECM into the cartilage defect in osteochondral defect rat knee joint. We believe that our proof-of-concept study will serve as a basis for investigating the potential of dECM obtained from iPSC-derived differentiated cells as a non-cellular resource for tissue regeneration and other future applications.
MeSH term(s)	Humans ; Rats ; Animals ; Chondrocytes/metabolism ; Induced Pluripotent Stem Cells ; Decellularized Extracellular Matrix ; Cartilage, Articular/physiology ; Extracellular Matrix/metabolism ; Cell Differentiation ; Chondrogenesis ; Tissue Engineering
Chemical Substances	Decellularized Extracellular Matrix
Language	English
Publishing date	2023-06-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2023.05.052
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Article ; Online: Application of Induced Pluripotent Stem Cells for Disease Modeling and 3D Model Construction: Focus on Osteoarthritis.

Hwang, Joel Jihwan / Choi, Jinhyeok / Rim, Yeri Alice / Nam, Yoojun / Ju, Ji Hyeon

Cells

2021 Volume 10, Issue 11

Abstract: Since their discovery in 2006, induced pluripotent stem cells (iPSCs) have shown promising potential, specifically because of their accessibility and plasticity. Hence, the clinical applicability of iPSCs was investigated in various fields of research. ... ...

Abstract	Since their discovery in 2006, induced pluripotent stem cells (iPSCs) have shown promising potential, specifically because of their accessibility and plasticity. Hence, the clinical applicability of iPSCs was investigated in various fields of research. However, only a few iPSC studies pertaining to osteoarthritis (OA) have been performed so far, despite the high prevalence rate of degenerative joint disease. In this review, we discuss some of the most recent applications of iPSCs in disease modeling and the construction of 3D models in various fields, specifically focusing on osteoarthritis and OA-related conditions. Notably, we comprehensively reviewed the successful results of iPSC-derived disease models in recapitulating OA phenotypes for both OA and early-onset OA to encompass their broad etiology. Moreover, the latest publications with protocols that have used iPSCs to construct 3D models in recapitulating various conditions, particularly the OA environment, were further discussed. With the overall optimistic results seen in both fields, iPSCs are expected to be more widely used for OA disease modeling and 3D model construction, which could further expand OA drug screening, risk assessment, and therapeutic capabilities.
MeSH term(s)	Cell Differentiation ; Humans ; Induced Pluripotent Stem Cells/pathology ; Models, Biological ; Osteoarthritis/pathology
Language	English
Publishing date	2021-11-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10113032
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Article: Lupus Heart Disease Modeling with Combination of Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Lupus Patient Serum.

Park, Narae / Rim, Yeri Alice / Jung, Hyerin / Nam, Yoojun / Ju, Ji Hyeon

International journal of stem cells

2021 Volume 15, Issue 3, Page(s) 233–246

Abstract: Background and objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease mainly affecting young women of childbearing age. SLE affects the skin, joints, muscles, kidneys, lungs, and heart. Cardiovascular complications are common ... ...

Abstract	Background and objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease mainly affecting young women of childbearing age. SLE affects the skin, joints, muscles, kidneys, lungs, and heart. Cardiovascular complications are common causes of death in patients with SLE. However, the complexity of the cardiovascular system and the rarity of SLE make it difficult to investigate these morbidities. Patient-derived induced pluripotent stem cells (iPSCs) serve as a novel tool for drug screening and pathophysiological studies in the absence of patient samples. Methods and results: We differentiated CMs from HC- and SLE-iPSCs using 2D culture platforms. SLE-CMs showed decreased proliferation and increased levels of fibrosis and hypertrophy marker expression; however, HC-and SLE-monolayer CMs reacted differently to SLE serum treatment. HC-iPSCs were also differentiated into CMs using 3D spheroid culture and anti-Ro autoantibody was treated along with SLE serum. 3D-HC-CMs generated more mature CMs compared to the CMs generated using 2D culture. The treatment of anti-Ro autoantibody rapidly increased the gene expression of fibrosis, hypertrophy, and apoptosis markers, and altered the calcium signaling in the CMs. Conclusions: iPSC derived cardiomyocytes with patient-derived serum, and anti-Ro antibody treatment could serve in effective autoimmune disease modeling including SLE. We believe that the present study might briefly provide possibilities on the application of a combination of patient-derived materials and iPSCs in disease modeling of autoimmune diseases.
Language	English
Publishing date	2021-12-31
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2914134-5
ISSN	2005-5447 ; 2005-3606
ISSN (online)	2005-5447
ISSN	2005-3606
DOI	10.15283/ijsc21158
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