• BMB Reports
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• v.56 no.2
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• pp.71-77
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• 2023

Cancers are one of the most dreaded diseases in human history and have been targeted by numerous trials including surgery, chemotherapy, radiation therapy, and anti-cancer drugs. Adult stem cells (ASCs), which can regenerate tissues and repair damage, have emerged as leading therapeutic candidates due to their homing ability toward tumor foci. Stem cells can precisely target malicious tumors, thereby minimizing the toxicity of normal cells and unfavorable side effects. ASCs, such as mesenchymal stem cells (MSCs), neural stem cells (NSCs), and hematopoietic stem cells (HSCs), are powerful tools for delivering therapeutic agents to various primary and metastatic cancers. Engineered ASCs act as a bridge between the tumor sites and tumoricidal reagents, producing therapeutic substances such as exosomes, viruses, and anti-cancer proteins encoded by several suicide genes. This review focuses on various anti-cancer therapies implemented via ASCs and summarizes the recent treatment progress and shortcomings.

• BMB Reports
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• v.48 no.12
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• pp.668-676
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• 2015

Pluripotent stem cells only exist in a narrow window during early embryonic development, whereas multipotent stem cells are abundant throughout embryonic development and are retainedin various adult tissues and organs. While pluripotent stem cell lines have been established from several species, including mouse, rat, and human, it is still challenging to establish stable multipotent stem cell lines from embryonic or adult tissues. Based on current knowledge, we anticipate that by manipulating extrinsic and intrinsic signaling pathways, most if not all types of stem cells can be maintained in a long-term culture. In this article, we summarize current culture conditions established for the long-term maintenance of authentic pluripotent and multipotent stem cells and the signaling pathways involved. We also discuss the general principles of stem cell maintenance and propose several strategies on the establishment of novel stem cell lines through manipulation of signaling pathways.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2005.07a
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• pp.48-48
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• 2005

• Molecules and Cells
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• v.45 no.11
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• pp.820-832
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• 2022

As a potential candidate to generate an everlasting cell source to treat various diseases, embryonic stem cells are regarded as a promising therapeutic tool in the regenerative medicine field. Cohesin, a multi-functional complex that controls various cellular activities, plays roles not only in organizing chromosome dynamics but also in controlling transcriptional activities related to self-renewal and differentiation of stem cells. Here, we report a novel role of the α-kleisin subunits of cohesin (RAD21 and REC8) in the maintenance of the balance between these two stem-cell processes. By knocking down REC8, RAD21, or the non-kleisin cohesin subunit SMC3 in mouse embryonic stem cells, we show that reduction in cohesin level impairs their self-renewal. Interestingly, the transcriptomic analysis revealed that knocking down each cohesin subunit enables the differentiation of embryonic stem cells into specific lineages. Specifically, embryonic stem cells in which cohesin subunit RAD21 were knocked down differentiated into cells expressing neural alongside germline lineage markers. Thus, we conclude that cohesin appears to control the fate determination of embryonic stem cells.

• International Journal of Stem Cells
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• v.16 no.3
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• pp.293-303
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• 2023

Background and Objectives: The physiological oxygen tension in fetal brains (~3%, physioxia) is beneficial for the maintenance of neural stem cells (NSCs). Sensitivity to oxygen varies between NSCs from different fetal brain regions, with midbrain NSCs showing selective susceptibility. Data on Hif-1𝛼/Notch regulatory interactions as well as our observations that Hif-1𝛼 and oxygen affect midbrain NSCs survival and proliferation prompted our investigations on involvement of Notch signalling in physioxia-dependent midbrain NSCs performance. Methods and Results: Here we found that physioxia (3% O₂) compared to normoxia (21% O₂) increased proliferation, maintained stemness by suppression of spontaneous differentiation and supported cell cycle progression. Microarray and qRT-PCR analyses identified significant changes of Notch related genes in midbrain NSCs after long-term (13 days), but not after short-term physioxia (48 hours). Consistently, inhibition of Notch signalling with DAPT increased, but its stimulation with Dll4 decreased spontaneous differentiation into neurons solely under normoxic but not under physioxic conditions. Conclusions: Notch signalling does not influence the fate decision of midbrain NSCs cultured in vitro in physioxia, where other factors like Hif-1𝛼 might be involved. Our findings on how physioxia effects in midbrain NSCs are transduced by alternative signalling might, at least in part, explain their selective susceptibility to oxygen.

• Genomics & Informatics
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• v.5 no.1
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• pp.1-5
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• 2007

Embryonic stem cells can be differentiated into various types of cells, requiring a tight regulation of transcription. Biomarkers related to each lineage of cells are used to guide the differentiation into neural or any other fates. In previous experiments, we reported the guided differentiation (GD)-specific genes by comparing profiles of random differentiation (RD). Interestingly 68% of differentially expressed genes in GD overlap with that of RD, which makes it difficult for us to separate the lineages by examining several markers. In this paper, we design a prediction model to identify the differentiation into neural fates from any other lineage. From the profiles of 11,376 genes, 203 differentially expressed genes between neural and random differentiation were selected by random variance T-test with 95% confidence and 5% false discovery rate. Based on support vector machine algorithm, we could select 79 marker genes from the 203 informative genes to construct the optimal prediction model. Here we propose a prediction model for the prediction of neural fates from random differentiation which is constructed with a perfect accuracy.

• The Korean Journal of Pain
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• v.32 no.4
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• pp.245-255
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• 2019

Stem cells are attracting attention as a key element in future medicine, satisfying the desire to live a healthier life with the possibility that they can regenerate tissue damaged or degenerated by disease or aging. Stem cells are defined as undifferentiated cells that have the ability to replicate and differentiate themselves into various tissues cells. Stem cells, commonly encountered in clinical or preclinical stages, are largely classified into embryonic, adult, and induced pluripotent stem cells. Recently, stem cell transplantation has been frequently applied to the treatment of pain as an alternative or promising approach for the treatment of severe osteoarthritis, neuropathic pain, and intractable musculoskeletal pain which do not respond to conventional medicine. The main idea of applying stem cells to neuropathic pain is based on the ability of stem cells to release neurotrophic factors, along with providing a cellular source for replacing the injured neural cells, making them ideal candidates for modulating and possibly reversing intractable neuropathic pain. Even though various differentiation capacities of stem cells are reported, there is not enough knowledge and technique to control the differentiation into desired tissues in vivo. Even though the use of stem cells is still in the very early stages of clinical use and raises complicated ethical problems, the future of stem cells therapies is very bright with the help of accumulating evidence and technology.

• Molecules and Cells
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• v.42 no.3
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• pp.200-209
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• 2019

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been used as promising tools for regenerative medicine, disease modeling, and drug screening. Traditional and common strategies for pluripotent stem cell (PSC) differentiation toward disease-relevant cell types depend on sequential treatment of signaling molecules identified based on knowledge of developmental biology. However, these strategies suffer from low purity, inefficiency, and time-consuming culture conditions. A growing body of recent research has shown efficient cell fate reprogramming by forced expression of single or multiple transcription factors. Here, we review transcription factor-directed differentiation methods of PSCs toward neural, muscle, liver, and pancreatic endocrine cells. Potential applications and limitations are also discussed in order to establish future directions of this technique for therapeutic purposes.

• Development and Reproduction
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• v.12 no.1
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• pp.87-95
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• 2008

Neural stem/precursor derived from pluripotent human embryonic stem cells (hESCs) has considerable therapeutic potential due to their ability to generate various neural cells which can be used in cell-replacement therapies for neurodegenerative diseases. However, production of neural cells from hESCs remains technically very difficult. Understanding neural-tube like rosette characteristic neural precursor cells from hESCs may provide useful information to increase the efficiency of hESC neural differentiation. Generally, neural rosettes were derived from differentiating hEBs in attached culture system, however this is time-consuming and complicated. Here, we examined if neural rosettes could be formed in suspension culture system by bypassing attachment requirement. First, we tested whether the size of hESC clumps affected the formation of human embryonic bodies (hEBs) and neural differentiation. We confirmed that hEBs derived from $500{\times}500\;{\mu}m$ square sized hESC clumps were effectively differentiated into neural lineage than those of the other sizes. To induce the rosette formation, regular size hEBs were derived by incubation of hESC clumps($500{\times}500\;{\mu}m$) in EB medium for 1 wk in a suspended condition on low attachment culture dish and further incubated for additional $1{\sim}2$ wks in neuroectodermal sphere(NES)-culture medium. We observed the neural tube-like rosette structure from hEBs after $7{\sim}10$ days of differentiation. Their identity as a neural precursor cells was assessed by measuring their expressions of neural precursor markers(Vimentin, Nestin, MSI1, MSI2, Prominin-1, Pax6, Sox1, N-cadherin, Otx2, and Tuj1) by RT-PCR and immunofluorescence staining. We also confirmed that neural rosettes could be terminally differentiated into mature neural cell types by additional incubation for $2{\sim}6$ wks with NES medium without growth factors. Neuronal(Tuj1, MAP2, GABA) and glial($S100{\beta}$ and GFAP) markers were highly expressed after $2{\sim}3$ and 4 wks of incubation, respectively. Expression of oligodendrocyte markers O1 and CNPase was significantly increased after $5{\sim}6$ wks of incubation. Our results demonstrate that rosette forming neural precursor cells could be successfully derived from suspension culture system and that will not only help us understand the neural differentiation process of hESCs but also simplify the derivation process of neural precursors from hESCs.

• Clinics in Shoulder and Elbow
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• v.15 no.2
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• pp.65-72
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• 2012

Purpose: To evaluate the differentiation potential of stem cells and their immunophenotype from 3 different sources. Methods: Our study involved three stem cell sources-subacromial bursal tissue, bone marrow, and umbilical cord blood. We obtained the subacromial bursal tissue and bone marrow from the patients undergoing shoulder surgery. After collecting the sample, we applied specific induction media for neurogenic, adipogenic and osteogenic differentiation. Also, flow-cytometry analysis was done to reveal the cell surface antigens. Results: We obtained 100% (8 cases) neural and adipogenic differentiation, but 62.5% (5 of 8 cases) osseous differentiation among the subacromial bursal tissue group. Bone marrow derived cells showed 100% neural (6 cases) and adipogenic (5 cases) differentiation, but 80% (4 of 5 cases) osseous differentiation. Umbilical cord blood derived cells revealed 97% (65 of 67 cases) neural, 53.7% (29 of 54 cases) adipogenic and 68.4% (39 of 57 cases) osseous differentiation. Immunophenotype analysis revealed that surface markers of bone marrow, subacromial bursal cell and umbilical cord blood derived mesenchymal stem cells are different from each other. Conclusions: Mesenchymal stem cells are potential agents in regenerative medicine and are characterized by expression of surface markers and by their differentiation potential. Our study with stem cells from subacromial bursal tissue, bone marrow and umbilical cord discovered that each stem cell has unique differentiation potential and function based on its origin. Various stem cells show multi-lineage differentiations in vitro which can be correlated to in vivo conditions.