• BMB Reports
• /
• 제55권1호
• /
• pp.20-29
• /
• 2022

Stem cell-based therapy is a promising approach for treating a variety of disorders, including acute brain insults and neurodegenerative diseases. Stem cells such as mesenchymal stem cells (MSCs) secrete extracellular vesicles (EVs), circular membrane fragments (30 nm-1 ㎛) that are shed from the cell surface, carrying several therapeutic molecules such as proteins and microRNAs. Because EV-based therapy is superior to cell therapy in terms of scalable production, biodistribution, and safety profiles, it can be used to treat brain diseases as an alternative to stem cell therapy. This review presents evidences evaluating the role of stem cell-derived EVs in stroke, traumatic brain injury, and degenerative brain diseases, such as Alzheimer's disease and Parkinson' disease. In addition, stem cell-derived EVs have better profiles in biocompatibility, immunogenicity, and safety than those of small chemical and macromolecules. The advantages and disadvantages of EVs compared with other strategies are discussed. Even though EVs obtained from native stem cells have potential in the treatment of brain diseases, the successful clinical application is limited by the short half-life, limited targeting, rapid clearance after application, and insufficient payload. We discuss the strategies to enhance the efficacy of EV therapeutics. Finally, EV therapies have yet to be approved by the regulatory authorities. Major issues are discussed together with relevant advances in the clinical application of EV therapeutics.

• International Journal of Oral Biology
• /
• 제38권4호
• /
• pp.161-167
• /
• 2013

Human dental pulp stem cells (DPSCs) are multi-potent mesenchymal stem cells that have several differentiation potentials. An understanding of thetissues that differentiate from these cells can provide insights for future regenerative therapeutics and tissue engineering strategies. The mesiodens is the most frequent form of supernumerary tooth from which DPSCs can differentiate into several lineages similar to cells from normal deciduous teeth. Recently, it has been shown that nanoscale structures can affect stem cell differentiation. In our presentstudy, we investigated the effects of a 250-nm nanoscale ridge/groove pattern array on the osteogenic and adipogenic differentiation of dental pulp cells from mesiodenscontaining human DPSCs. To this end, the expression of lineage specific markers after differentiation induction was analyzed by lineage specific staining and RT-PCR. The nanoscale pattern arrayed surface showed apositive effect on the adipogenic differentiation of DPSCs. There was no difference between nanoscale pattern arrayed surface and conventional surface groups onosteogenic differentiation. In conclusion, the nanoscale ridge/groove pattern arrayed surface can be used to enhance the adipogenic differentiation of DPSCs derived from mesiodens. This finding provides an improved understanding of the effects of topography on cell differentiation as well as the potential use of supernumerary tooth in regenerative dental medicine.

• 한국진공학회:학술대회논문집
• /
• 한국진공학회 2015년도 제49회 하계 정기학술대회 초록집
• /
• pp.223.2-223.2
• /
• 2015

Polyurethane acrylate (PUA) has been introduced to utilize as a mold material for sub-100 nm lithography as it provides advantages of stiffness for nanostructure formation, short curing time, flexibility for large area replication and transparency for relevant biomedical applications. Due to the ability to fabricate nanostructures on PUA, there have been many efforts to mimic extracellular matrix (ECM) using PUA especially in a field of tissue engineering. It has been demonstrated that PUA is useful for investigating the nanoscale-topographical effects on cell behavior in vitro such as cell attachment, spreading on a substrate, proliferation, and stem cell fate with various types of nanostructures. In this study, we have conducted surface modification of PUA films with micro/nanostructures on their surfaces using plasma treatment. In general, it is widely known that the plasma treated surface increases cell attachment as well as adsorption of ECM materials such as fibronectin, collagen and gelatin. Effect of plasma treatment on PUA especially with surface of micro/nanostructures needs to be understood further for its biomedical applications. We have evaluated the modified PUA film as a culture platform using adipose derived stem cells. Then, the behavior of stem cells and the level of adsorbed protein have been analyzed.

• Journal of Korean Biological Nursing Science
• /
• 제23권1호
• /
• pp.1-10
• /
• 2021

Purpose: To verify the anti-microbiotic activity and to develop eco-friendly surface disinfectants using the Opuntia ficus-indica extract. Methods: The stem and fruits of the Opuntia cultivated in Jeju Island were extracted with hot water, 70% EtOH and 100% MeOH, respectively. To examine the antimicrobial activity of the extracts, gram positive bacteria (Bacillus subtilis, Staphylococcus aureus), gram negative bacteria (Escherichia coli, Salmonella typhimurium), yeast (Candida albicans), mold (Aspergillus flavus) and antibiotic resistant bacteria (E. coli, S. aureus) were measured to form a clear zone. Results: The antibacterial activity of the fruit extract was higher than that of the stem extract, and the antibacterial activity of the 100% MeOH (FM) extract and the 70% EtOH (FE) extract of the palm cactus fruit was suitable for the surface disinfectant overall, and clear-zone formed even at relatively low concentrations (250 mg/mL). The FM and FE have antibacterial activity against various bacteria, therefore they can be used as disinfectants. Conclusion: The antimicrobial activity of Opuntia ficus-indica extract from Jeju Island by stem and fruit was determined at relatively low concentrations (250 mg/mL). The Opuntia ficus-indica extract will be useful for surface disinfectants dissolving the patients' bath, oral gargling, and powdered powder in water or ethanol in appropriate concentrations.

• Clinics in Shoulder and Elbow
• /
• 제15권2호
• /
• pp.65-72
• /
• 2012

목적: 세가지 기원의 줄기 세포 분화능과 면역표현형을 평가하고자 하였다. 대상 및 방법: 견봉하 점액낭과 골수, 탯줄 혈액 세 개의 군에서 세포를 채취하였다. 견봉하 점액낭과 골수는 견관절 수술 환자군에게 임상적 동의 하에 수술중 채취하였다. 각각의 채취된 세포 및 탯줄 혈액에 대하여 계대 배양을 시행하여 신경 분화군, 지방 분화군, 골 분화군을 평가하였으며 세포 표면 항체를 밝히기 위해 유동세포분석법을 이용하였다. 결과: 견봉하 점액낭 유래 세포에서는 신경분화와 지방 분화는 8예 모두 (100%)에서, 골분화는 8례 중 5예 (62.5%)에서 성공할 수 있었으며 골수 유래 세포의 경우 신경 및 지방 분화 유도한 6례 및 5예 모두 (100%) 분화에 성공하였으나 골분화 유도는 5예 중 4예 (80%)에서 얻을 수 있었다. 반면 탯줄 유래 세포 분화 연구의 경우 신경 분화 유도 67례 중 65예 (97%)에서 지방 분화 연구 54예 중 29예 (53.7%)에서 골 분화 연구 57예 중 39예 (68.4%)에서 성공할 수 있었다. 결론: 탯줄 유래 줄기세포의 분화능과 비교하였을 때 견봉하 점액낭 및 골수 유래 줄기세포의 분화능이 우수함을 알 수 있으며 이는 향후 세포 치료에 있어서 안정성 있는 치료 제공자가 될 수 있을 것으로 보이며 향후 생체 실험 연구의 참고 자료로서도 가치가 있을 것으로 보인다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권2호
• /
• pp.437-442
• /
• 2015

Aim: To establish a pancreatic cancer stem cell model using human pancreatic cancer cells in nude mice to provide a platform for pancreatic cancer stem cell research. Materials and Methods: To establish pancreatic cancer xenografts using human pancreatic cancer cell line SW1990, nude mice were randomly divided into control and gemcitabine groups. When the tumor grew to a volume of $125mm^3$, they treated with gemcitabine at a dose of 50mg/kg by intraperitoneal injection of 0.2ml in the gemcitabine group, while the mice in control group were treated with the same volume of normal saline. Gemcitabine was given 2 times a week for 3 times. When the model was established, the proliferation of pancreatic cancer stem cells was observed by clone formation assay, and the protein and/or mRNA expression of pancreatic stem cell surface markers including CD24, CD44, CD133, ALDH, transcription factors containing Oct-4, Sox-2, Nanog and Gli, the key nuclear transcription factor in Sonic Hedgehog signaling pathway was detected by Western blot and/or RT-PCR to verify the reliability of this model. Results: This model is feasible and safe. During the establishment, no mice died and the weight of nude mice maintained above 16.5g. The clone forming ability in gemcitabine group was stronger than that of the control group (p<0.01). In gemcitabine group, the protein expression of pancreatic cancer stem cell surface markers including CD44, and ALDH was up-regulated, the protein and mRNA expression of nuclear transcription factor including Oct-4, Sox-2 and Nanog was also significantly increased (P<0.01). In addition, the protein expression of key nuclear transcription factor in Sonic Hedgehog signaling pathway, Gli-1, was significantly enhanced (p<0.01). Conclusions: The pancreatic cancer stem cell model was successfully established using human pancreatic cancer cell line SW1990 in nude mice. Gemcitabine could enrich pancreatic cancer stem cells, simultaneously accompanied by the activation of Sonic Hedgehog signaling pathway.

• Journal of Microbiology
• /
• 제45권6호
• /
• pp.547-552
• /
• 2007

Previously, we generated monoclonal antibodies (MAbs) that bound to the surface of human embryonic stem cells (hESCs) in an attempt to discover new hESC-specific surface markers. In this study, MAb 47-235 (IgG1, ${\kappa}$) was selected for further characterization. The MAb bound to the surface of undifferentiated hESCs but did not bind to mouse ESCs or mouse embryonic fibroblast cells in flow cytometric analysis. The antibody immunoprecipitated a 47 kDa protein from the lysates of cell surface-biotinylated hESCs. Identification of the protein by quadrupole time of flight tandem mass spectrometry revealed that 47-235 binds to Ag 243-5 protein of Mycoplasma arginini. BM-Cyclin treatment of the hESCs that reacted with 47-235 resulted in loss of mycoplasma DNA and the reactivity to 47-235. Nevertheless, the hESCs that were reactive to 47-235 maintained self-renewal and pluripotency and thus could be differentiated into three embryonic germ layers.

• 대한의용생체공학회:의공학회지
• /
• 제29권3호
• /
• pp.212-221
• /
• 2008

The total hip replacement (THR) has been used as the most effective way to restore the function of damaged hip joint. However, various factors have caused some side effects after the THR. Unfortunately, the success of the THR have been decided only by the proficiency of surgeons so far. Hence, It is necessary to find the way to minimize the side effect caused by those factors. The purpose of this study was to suggest the definite data, which can be used to design and choose the optimal hip implant. Using finite element analysis (FEA), the biomechanical condition of bone cement was evaluated. Stress patterns were analyzed in three conditions: cement mantle, procimal femur and stem-cement contact surface. Additionally, micro-motion was analyzed in the stem-cement contact surface. The 3-D femur model was reconstructed from 2-D computerized tomography (CT) images. Raw CT images were preprocessed by image processing technique (i.e. edge detection). In this study, automated edge detection system was created by MATLAB coding for effective and rapid image processing. The 3-D femur model was reconstructed based on anatomical parameters. The stem shape was designed using that parameters. The analysis of the finite element models was performed with the variation of parameters. The biomechanical influence of each parameter was analyzed and derived optimal parameters. Moreover, the results of FE A using commercial stem model (Zimmer's V erSys) were similar to the results of stem model that was used in this study. Through the study, the improved designs and optimal factors for clinical application were suggested. We expect that the results can suggest solutions to minimize various side effects.

• 대한의생명과학회지
• /
• 제19권4호
• /
• pp.295-302
• /
• 2013

Some of the pituitary adenomas are invasive and spread into neighboring tissues. In previous studies, the invasion of pituitary adenomas is thought to be associated with epithelial-mesenchymal transition (EMT). In addition to that, we thought that mesenchymal stem cells (MSCs) exist in relevant microenvironment in pituitary adenoma. However, it has been little known about the existence of MSCs from pituitary adenoma. So we investigated whether mesenchymal stem-like cells (MSLCs) can be isolated from the pituitary adenoma specimen. We isolated and cultured candidate MSLCs from the fresh pituitary adenoma specimen with the same protocols used in culturing bone marrow derived MSCs (BM-MSCs). The cultured candidate MSLCs were analyzed by fluorescence-activated cell sorting (FACS) for surface markers associated with MSCs. Candidate MSLCs were exposed to mesenchymal differentiation conditions to determine the mesenchymal differentiation potential of these cells. To evaluate the tumorigenesis of candidate MSLCs from pituitary adenoma, we implanted these cells into the brain of athymic nude mice. We isolated cells resembling BM-MSCs named pituitary adenoma stroma mesenchymal stem-like cells (PAS-MSLCs). PAS-MSLCs were spindle shaped and had adherent characteristics. FACS analysis identified that the PAS-MSLCs had a bit similar surface markers to BM-MSCs. Isolated cells expressed surface antigen, positive for CD105, CD75, and negative for CD45, NG2, and CD90. We found that these cells were capable of differentiation into adipocytes, osteocytes and chondrocytes. Tumor was not developed in the nude mice brains that were implanted with the PAS-MSLCs. In this study, we showed that MSLCs can be isolated from a pituitary adenoma specimen which is not tumorigenic.

• 생체재료학회지
• /
• 제22권4호
• /
• pp.337-345
• /
• 2018

Background: Human mesenchymal stem cells (hMSCs) are, due to their pluripotency, useful sources of cells for stem cell therapy and tissue regeneration. The phenotypes of hMSCs are strongly influenced by their microenvironment, in particular the extracellular matrix (ECM), the composition and structure of which are important in regulating stem cell fate. In reciprocal manner, the properties of ECM are remodeled by the hMSCs, but the mechanism involved in ECM remodeling by hMSCs under topographical stimulus is unclear. In this study, we therefore examined the effect of nanotopography on the expression of ECM proteins by hMSCs by analyzing the quantity and structure of the ECM on a nanogrooved surface. Methods: To develop the nanoengineered, hMSC-derived ECM, we fabricated the nanogrooves on a coverglass using a UV-curable polyurethane acrylate (PUA). Then, hMSCs were cultivated on the nanogrooves, and the cells at the full confluency were decellularized. To analyze the effect of nanotopography on the hMSCs, the hMSCs were re-seeded on the nanoengineered, hMSC-derived ECM. Results: hMSCs cultured within the nano-engineered hMSC-derived ECM sheet showed a different pattern of expression of ECM proteins from those cultured on ECM-free, nanogrooved surface. Moreover, hMSCs on the nano-engineered ECM sheet had a shorter vinculin length and were less well-aligned than those on the other surface. In addition, the expression pattern of ECM-related genes by hMSCs on the nanoengineered ECM sheet was altered. Interestingly, the expression of genes for osteogenesis-related ECM proteins was downregulated, while that of genes for chondrogenesis-related ECM proteins was upregulated, on the nanoengineered ECM sheet. Conclusions: The nanoengineered ECM influenced the phenotypic features of hMSCs, and that hMSCs can remodel their ECM microenvironment in the presence of a nanostructured ECM to guide differentiation into a specific lineage.