• Molecular & Cellular Toxicology
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• 제3권2호
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• pp.77-84
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• 2007

Millions of individuals worldwide are currently afflicted with neurodegenerative disorders such as Parkinson's disease and multiple sclerosis which are caused by the death of specific types of specialized cells in the Central Nervous System (CNS). Recently, Neural Stem Cells (NSCs) are able to replace these dead cells with new functional cells, thereby providing a cure for devastating neural diseases. The clinical use of neural stem cells (NSCs) for the treatment of neurological diseases requires overcoming the scarcity of the initial in vivo NSC population. Thus, we developed a novel 3-dimentional cellular automata model for optimum production of neural stem cells and their derivatives in large scale to treat neurodegenerative disorder patients.

• International Journal of Stem Cells
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• 제15권2호
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• pp.155-163
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• 2022

Background and Objectives: Mesenchymal stem cells (MSCs) have immunomodulatory function and participate in the pathogenesis of many immunoregulation-related diseases, including psoriasis. Previously, we found that MSCs from psoriatic lesions overexpress the proinflammatory microRNA, miR-155 and exhibit a decreased immunosuppressive capacity. But the origin of these aberrant characteristics is still not clear. To investigate whether inflammatory cytokines in serum and peripheral blood mononuclear cells (PBMCs) from psoriatic patients can regulate the expression patterns of immunoregulation-related cytokines and the immunoregulation function of MSCs. Methods and Results: Normal dermal mesenchymal stem cells (nDMSCs) were treated with serum or PBMCs derived from patients with psoriasis or healthy donors. Expression of miR-155 and immunoregulation-related genes in each MSCs were measured using real-time PCR or western-blot. Meanwhile, the immunosuppressive capacity of DMSCs was evaluated by its inhibitory ability on proliferation of activated PBMCs. Compared to control serum, psoriatic serum significantly increased the expression levels of miR-155 (27.19±2.40 vs. 3.51±1.19, p<0.001), while decreased TAB₂ expression (0.28±0.04 vs. 0.72±0.20, p<0.01) in DMSCs. Expression levels of immunoregulation-related genes such as PGE₂, IL-10, and TLR4 were also markedly down-regulated following the psoriatic serum treatment. Those DMSCs treated with healthy serum could inhibit PBMC proliferation, while those psoriatic serum-treated DMSCs could not inhibit PBMC proliferation effectively. Conclusions: Psoriatic serum up-regulate the expression of miR-155, down-regulate the expression of immunoregulation-related genes (PGE₂, IL-10, and TLR4) in DMSCs, and along with the inhibition of the immunosuppressive function of MSCs.

• 대한수의학회지
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• 제53권2호
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• pp.109-115
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• 2013

Cancers are mainly sustained by a small pool of neoplastic cells, known as cancer stem cells or tumorinitiating cells. These cells possess the ability to self-renew and proliferate, and are thus able to form the tumor. In the present study cells that correspond to cancer stem cells in mammary and liver cancers in animals were identified by the expression of CD133, CD44, CK7, and OCT4 using immunochemistry. As a result, we found with CD133+ and CD44+ cancer stem cell-like phenotypes in mouse and canine hepatocellular carcinoma and canine mammary gland tumors. However, CK7+ and OCT4+ cells were not identified in animal mammary and liver cancer. CD133+ and CD44+ cells are wellknown stem cell lines and play key roles in development and metastasis in human cancer. These findings suggest that cancer stem cells are involved in animal tumorigenesis and may provide insight into mechanisms in cancer development as well as cancer diagnostics.

• International Journal of Stem Cells
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• 제15권2호
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• pp.122-135
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• 2022

Background and Objectives: Endothelial progenitor cells (EPCs) and endothelial cells (ECs) have been applied in the clinic to treat pulmonary arterial hypertension (PAH), a disease characterized by disordered pulmonary vasculature. However, the lack of sufficient transplantable cells before the deterioration of disease condition is a current limitation to apply cell therapy in patients. It is necessary to differentiate pluripotent stem cells (PSCs) into EPCs and identify their characteristics. Methods and Results: Comparing previously reported methods of human PSCs-derived ECs, we optimized a highly efficient differentiation protocol to obtain cells that match the phenotype of isolated EPCs from healthy donors. The protocol is compatible with chemically defined medium (CDM), it could produce a large number of clinically applicable cells with low cost. Moreover, we also found PSCs-derived EPCs express CD133, have some characteristics of mesenchymal stem cells and are capable of homing to repair blood vessels in zebrafish xenograft assays. In addition, we further revealed that IPAH PSCs-derived EPCs have higher expression of proliferation-related genes and lower expression of immune-related genes than normal EPCs and PSCs-derived EPCs through microarray analysis. Conclusions: In conclusion, we optimized a highly efficient differentiation protocol to obtain PSCs-derived EPCs with the phenotypic and molecular characteristics of EPCs from healthy donors which distinguished them from EPCs from PAH.

• 생명과학회지
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• 제34권6호
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• pp.418-425
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• 2024

고형암은 여러 세포 유형의 이질적인 집단으로 구성되며, 암줄기세포는 자가 재생과 분화의 특성을 가지고 있다. 암줄기세포에서는 자가재생을 조절하는 줄기세포 신호전달체계가 과도하게 활성화되어 있어 암줄기세포는 암세포의 증식과 암 진행에 중요하다. 암줄기세포의 정의는 급성골수성백혈병에 의해 처음 제안되었으며, 다양한 연구를 통해 세포 표면 표지 발현에 따라 암 줄기세포를 분류할 수 있게 되었다. 또한, 암줄기세포는 종양 미세환경에서 잠재력을 보존하고 있고, 다양한 종양 미세환경 세포 유형은 정지 상태의 암줄기 세포를 유지하고 암 성장의 조절자 역할을 한다. 현재 사용되는 암 치료 방법은 증식성 세포를 표적으로 하기 때문에 치료에, 저항성을 가지는 휴지기 상태의 암 줄기세포는 재발이나 전이의 위험을 증가시키며, 종양 미세환경의 다양한 신호전달체계는 혈관계와 세포 외 기질을 리모델링함으로써 종양 지지 환경으로의 변화를 유도한다. 따라서, 암을 효과적으로 치료하려면 암줄기세포와 종양 미세환경을 표적 치료해야 하며, 종양 미세환경이 어떻게 면역 반응의 재프로그램을 유도하여 암의 성장, 면역 저항성 및 전이를 촉진하는지 이해하는 것이 중요하다. 따라서 본 총설을 통해 종양 미세환경에서 면역억제를 강화할 수 있는 세포 및 분자 메커니즘에 대한 현재 및 새로운 개념을 요약하고자 한다.

• Archives of Plastic Surgery
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• 제34권5호
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• pp.537-542
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• 2007

Purpose: Adipose tissue contains a population of pluripotent stem cells capable of differentiating along multiple mesenchymal cell lineages. It is well known that fat depots from different part of our body shows different nature not only in morphological aspect but also physiologic aspect. The authors compared the adipogenic potentials and osteogenic potentials of adipose stem cells from different anatomical sites of human. Methods: After laparotomy by surgery team, the authors isolated these adipose stem cells successfully from 7 men with an average age of 58, and induced differentiation along adipogenic and osteogenic lineages in vitro. On the 14th day, cells cultured in adipogenic media differentiated into adipocytes in vitro, as evidenced by positive Oil Red O staining of lipid vacuoles. On the 21st day, cells cultured in osteogenic media differentiated into osteoblasts in vitro as demonstrated by Alizarin red staining of a calcified extracellular matrix. Results: After exposure to adipogenic and osteogenic differentiation medium, subcutaneous adipose stem cells were found to possess greater adipogenic and osteogenic potentials than cells isolated from visceral adipose tissues. Conclusion: This study indicates that adipogenic and osteogenic potentials of adipose stem cells vary by their anatomical sites, with subcutaneous adipose stem cells exhibiting higher adipogenic and osteogenic potential than those isolated from visceral fat.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.4849-4852
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• 2015

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been investigated as an effective agent to treat various cancers. Cancer stem cells are resistant to TRAIL treatment, but the mechanism of TRAIL resistance remains unknown. In this study, brain cancer stem cells were isolated by CD133 magnetic sorting, and the number of CD133 positive cells detected by flow cytometry. The self-renewing capacity of brain cancer stem cells was examined by a neurosphere formation assay, and the percentage of cell death after TRAIL treatment was examined by an MTS assay. Expression of DR5, FADD, caspase 8 and BCL2 proteins was detected by western blot. The amount of CD133 positive cells was enriched to 71% after CD133 magnetic sorting. Brain cancer stem cell neurosphere formation was significantly increased after TRAIL treatment. TRAIL treatment also reduced the amount of viable cells and this decrease was inhibited by a caspase 8 inhibitor or by the pan-caspase inhibitor z-VAD (P<0.05). Brain cancer stem cells expressed lower levels caspase 8 protein and higher levels of BCL2 protein when compared with CD133 negative cells (P<0.05). Our data suggest that TRAIL resistance is related to overexpression of BCL2 and low expression of caspase 8 which limit activation of caspase 8 in brain cancer stem cells.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제32권4호
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• pp.327-333
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• 2006

Future cell-based therapies such as tissue engineering will benefit from a source of autogenous pluripotent stem cells. There are embryonic stem cells (ESC) and autologous adult stem cells, two general types of stem cells potentilally useful for these applications. But practical use of ESC is limited due to potential problems of cell regulation and ethical considerations. To get bone marrow stem cells is relatively burden to patients because of pain, anesthesia requirement. The ideal stem cells are required of such as the following advantages: easy to obtain, minimal patient discomfort and a capability of yielding enough cell numbers. Adipose autologus tissue taken from intraoral fatty pad or abdomen may represent such a source. Our study designed to demonstrate the ability of human adipose tissue-derived stromal cells (hATSC) from human abdominal adipose tissue diffentiating into osteocyte and adipocyte under culture in vitro conditions. As a result of experiment, we identified stromal cell derived adipose tissue has the multilineage potentiality under appropriate culture conditions. And the adipose stromal cells expressed several mesenchymal stem cell related antigen (CD29, CD44) reactions. Secondary, we compared the culture results of a group of hATSC stimulated with TGF-${\beta}$1, bFGF with a hATSC group without growth factors to confirm whether cytokines have a important role of the proliferation in osteogenic differentiation. The role of cytokines such as TGF-${\beta}$1, bFGF increased hATSC's osteogenic differentiation especially when TGF-${\beta}$1 and bFGF were used together. These results suggest that adipose stromal cells with growth factors could be efficiently available for cell-based bone regeneration.

• Reproductive and Developmental Biology
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• 제33권4호
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• pp.263-271
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• 2009

Cardiovascular diseases (CVDs) are one of the most cause of death around the world and fields of interest for cardiac stem cells. Also, current use of terminally differentiated adult cardiomyocytes for CVDs has limited regenerative capacity therefore any significant cell loss may result in the development of progressive heart failure. Human embryonic stem cells (hESCs) derived from blastocyst-stage embryos spontaneously have ability to differentiate via embryo-like aggregates (endoderm, ectoderm and mesoderm) in vitro into various cell types including cardiomyocyte. However, most effective molecule or optimized condition which can induce cardiac differentiation of hESCs is rarely studied. In this study, we developed both spontaneous and inductive cardiomyocyte-like cells differentiation from hESCs by treatment of induced-factors, 5-azacytidine, BMP-4 and cardiogenol C. On the one hand, spontaneous and inductive cardiomyocyte-like cells showed that cardiac markers are expressed for further analysis by RT-PCR and immunocytochemistry. Interestingly, BMP-4 greatly improved homogeneous population of the cardiomyocyte-like cells from hESCs CHA15 and H09. In conclusion, we verified that spontaneously differentiated cells showed cardiac specific markers which characterize cardiac cells, treated extrinsic factors can manage cellular signals and found that hESCs can undergo differentiation into cardiomyocytes better than spontaneous group. This finding offers an insight into the inductive factor of differentiated cardiomyocytes and provides some helpful information that may offer the potential of cardiomyocytes derived from hESCs using extrinsic factors.

• Journal of Periodontal and Implant Science
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• 제49권4호
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• pp.258-267
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• 2019

Purpose: Increased bone regeneration has been achieved through the use of stem cells in combination with graft material. However, the survival of transplanted stem cells remains a major concern. The purpose of this study was to evaluate the viability of transplanted mesenchymal stem cells (MSCs) at an early time point (24 hours) based on the type and form of the scaffold used, including type I collagen membrane and synthetic bone. Methods: The stem cells were obtained from the periosteum of the otherwise healthy dental patients. Four symmetrical circular defects measuring 6 mm in diameter were made in New Zealand white rabbits using a trephine drill. The defects were grafted with 1) synthetic bone (${\beta}$-tricalcium phosphate/hydroxyapatite [${\beta}-TCP/HA$]) and $1{\times}10^5MSCs$, 2) collagen membrane and $1{\times}10^5MSCs$, 3) ${\beta}-TCP/HA+collagen$ membrane and $1{\times}10^5MSCs$, or 4) ${\beta}-TCP/HA$, a chipped collagen membrane and $1{\times}10^5MSCs$. Cellular viability and the cell migration rate were analyzed. Results: Cells were easily separated from the collagen membrane, but not from synthetic bone. The number of stem cells attached to synthetic bone in groups 1, 3, and 4 seemed to be similar. Cellular viability in group 2 was significantly higher than in the other groups (P<0.05). The cell migration rate was highest in group 2, but this difference was not statistically significant (P>0.05). Conclusions: This study showed that stem cells can be applied when a membrane is used as a scaffold under no or minimal pressure. When space maintenance is needed, stem cells can be loaded onto synthetic bone with a chipped membrane to enhance the survival rate.