• 생명과학회지
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• 제30권4호
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• pp.394-401
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• 2020

배아줄기세포는 만능세포이기 때문에 동물에게 주입되면 종양으로 발달할 수도 있다. 따라서 연구자들은 종양 형성으로부터 비교적 자유로운 성체세포로부터 세포 특이적 줄기세포(성체줄기세포)를 확보하는데 관심을 두고 있다. 성체줄기세포는 제한적으로 세포분열을 할 수 있고 지정된 특정 세포로만 발달할 수 있다. 포유동물에서 각 조직의 세포들은 자연적 생리조건하에서는 역분화 혹은 교차분화에 의해 성체줄기세포로 전환되지 않는다. 따라서 일본 연구자들에 의하여 2006년 성체세포의 리프로그램에 의한 유도만능줄기세포(iPSCs) 기술이 소개되어 성체줄기세포 연구의 새로운 장을 열었다. 비록 연구현장에서 iPSCs 기술이 폭 넓게 이용되지만, 리프로그램의 안정성뿐만 아니라 유전체에 외래유전자의 도입 등의 문제점도 있다. Reversine은 iPSCs 보다 2년 앞서 발견된 작은 화학적 합성 분자인 퓨린 유사체이다. Reversine은 분화된 세포를 리프로그램에 의한 역분화를 유도하여 다능성 줄기세포로 전환시킬 수 있으며, 적절한 분화조건하에서 다른 세포로 교차분화를 유도할 수도 있다. 따라서 reversine은 iPSCs가 가지고 있는 문제점을 극복하고 화학적인 방법을 이용하여 성체세포를 다능성 줄기세포로 전환시킬 수 있는 물질로 활용될 수 있다. Reversine이 백색지방세포를 갈색지방형세포(beige cell)로 전변시켜 열발산에 의한 에너지소비를 촉진함을 제시하여 항비만인자로서 그 가능성을 열어 놓았다. Reversine은 세포 역분화의 기능적 역할 이외에 항암 인자로서 또 다른 기능들이 보고되고 있어 앞으로 여러 분야에서 그 이용성이 기대되는 물질이다.

• 대한생식의학회:학술대회논문집
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• 대한불임학회 2005년도 제48차 춘계 학술대회
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• pp.125.1-125.1
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• 2005

• 대한치과교정학회지
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• 제42권6호
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• pp.307-317
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• 2012

Objective: The purpose of this study was to investigate the isolation and characterization of multipotent human periodontal ligament (PDL) stem cells and to assess their ability to differentiate into bone, cartilage, and adipose tissue. Methods: PDL stem cells were isolated from 7 extracted human premolar teeth. Human PDL cells were expanded in culture, stained using anti-CD29, -CD34, -CD44, and -STRO-1 antibodies, and sorted by fluorescent activated cell sorting (FACS). Gingival fibroblasts (GFs) served as a positive control. PDL stem cells and GFs were cultured using standard conditions conducive for osteogenic, chondrogenic, or adipogenic differentiation. Results: An average of $152.8{\pm}27.6$ colony-forming units was present at day 7 in cultures of PDL stem cells. At day 4, PDL stem cells exhibited a significant increase in proliferation (p < 0.05), reaching nearly double the proliferation rate of GFs. About $5.6{\pm}4.5%$ of cells in human PDL tissues were strongly STRO-1-positive. In osteogenic cultures, calcium nodules were observed by day 21 in PDL stem cells, which showed more intense calcium staining than GF cultures. In adipogenic cultures, both cell populations showed positive Oil Red O staining by day 21. Additionally, in chondrogenic cultures, PDL stem cells expressed collagen type II by day 21. Conclusions: The PDL contains multipotent stem cells that have the potential to differentiate into osteoblasts, chondrocytes, and adipocytes. This adult PDL stem cell population can be utilized as potential sources of PDL in tissue engineering applications.

• The Korean Journal of Physiology and Pharmacology
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• 제21권2호
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• pp.153-160
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• 2017

In this study, we aim to determine the in vivo effect of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) on neuropathic pain, using three, principal peripheral neuropathic pain models. Four weeks after hUCB-MSC transplantation, we observed significant antinociceptive effect in hUCB-MSC-transplanted rats compared to that in the vehicle-treated control. Spinal cord cells positive for c-fos, CGRP, p-ERK, p-p 38, MMP-9 and MMP 2 were significantly decreased in only CCI model of hUCB-MSCs-grafted rats, while spinal cord cells positive for CGRP, p-ERK and MMP-2 significantly decreased in SNL model of hUCB-MSCs-grafted rats and spinal cord cells positive for CGRP and MMP-2 significantly decreased in SNI model of hUCB-MSCs-grafted rats, compared to the control 4 weeks or 8weeks after transplantation (p<0.05). However, cells positive for TIMP-2, an endogenous tissue inhibitor of MMP-2, were significantly increased in SNL and SNI models of hUCB-MSCs-grafted rats. Taken together, subcutaneous injection of hUCB-MSCs may have an antinociceptive effect via modulation of pain signaling during pain signal processing within the nervous system, especially for CCI model. Thus, subcutaneous administration of hUCB-MSCs might be beneficial for improving those patients suffering from neuropathic pain by decreasing neuropathic pain activation factors, while increasing neuropathic pain inhibition factor.

• 식물조직배양학회지
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• 제27권6호
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• pp.423-428
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• 2000

In 1997 when cloned sheep Dolly and soon after Polly were born, it had become head-line news because in the former the nucleus that gave rise to the lamb came from cells of six-year-old adult sheep and in the latter case a foreign gene was inserted into the donor nucleus to make the cloned sheep produce human protein, factor IX, in e milk. In the last few years, once the realm of science fiction, cloned mammals especially in livestock have become almost commonplace. What the press accounts often fail to convey, however, is that behind every success lie hundreds of failures. Many of the nuclear-transferred egg cells fail to undergo normal cell divisions. Even when an embryo does successfully implant in the womb, pregnancy often ends in miscarriage. A significant fraction of the animals that are born die shortly after birth and some of those that survived have serious developmental abnormalities. Efficiency remains at less than one % out of some hundred attempts to clone an animal. These facts show that something is fundamentally wrong and enormous hurdles must be overcome before cloning becomes practical. Cloning researchers now tent to put aside their effort to create live animals in order to probe the fundamental questions on cell biology including stem cells, the questions of whether the hereditary material in the nucleus of each cell remains intact throughout development, and how transferred nucleus is reprogrammed exactly like the zygotic nucleus. Stem cells are defined as those cells which can divide to produce a daughter cell like themselves (self-renewal) as well as a daughter cell that will give rise to specific differentiated cells (cell-differentiation). Multicellular organisms are formed from a single totipotent stem cell commonly called fertilized egg or zygote. As this cell and its progeny undergo cell divisions the potency of the stem cells in each tissue and organ become gradually restricted in the order of totipotent, pluripotent, and multipotent. The differentiation potential of multipotent stem cells in each tissue has been thought to be limited to cell lineages present in the organ from which they were derived. Recent studies, however, revealed that multipotent stem cells derived from adult tissues have much wider differentiation potential than was previously thought. These cells can differentiate into developmentally unrelated cell types, such as nerve stem cell into blood cells or muscle stem cell into brain cells. Neural stem cells isolated from the adult forebrain were recently shown to be capable of repopulating the hematopoietic system and produce blood cells in irradiated condition. In plants although the term$\boxDr$ stem cell$\boxUl$is not used, some cells in the second layer of tunica at the apical meristem of shoot, some nucellar cells surrounding the embryo sac, and initial cells of adventive buds are considered to be equivalent to the totipotent stem cells of mammals. The telomere ends of linear eukaryotic chromosomes cannot be replicated because the RNA primer at the end of a completed lagging strand cannot be replaced with DNA, causing 5' end gap. A chromosome would be shortened by the length of RNA primer with every cycle of DNA replication and cell division. Essential genes located near the ends of chromosomes would inevitably be deleted by end-shortening, thereby killing the descendants of the original cells. Telomeric DNA has an unusual sequence consisting of up to 1,000 or more tandem repeat of a simple sequence. For example, chromosome of mammal including human has the repeating telomeric sequence of TTAGGG and that of higher plant is TTTAGGG. This non-genic tandem repeat prevents the death of cell despite the continued shortening of chromosome length. In contrast with the somatic cells germ line cells have the mechanism to fill-up the 5' end gap of telomere, thus maintaining the original length of chromosome. Cem line cells exhibit active enzyme telomerase which functions to maintain the stable length of telomere. Some of the cloned animals are reported prematurely getting old. It has to be ascertained whether the multipotent stem cells in the tissues of adult mammals have the original telomeres or shortened telomeres.

• BMB Reports
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• 제48권6호
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• pp.319-323
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• 2015

Mesenchymal stem cells (MSCs) are multipotent stem cells capable of differentiating into adipocytes, osteoblasts, or chondrocytes. A mutually inhibitory relationship exists between osteogenic and adipogenic lineage commitment and differentiation. Such cell fate decision is regulated by several signaling pathways, including Wnt and bone morphogenetic protein (BMP). Accumulating evidence indicates that microRNAs (miRNAs) act as switches for MSCs to differentiate into either osteogenic or adipogenic lineage. Different miRNAs have been reported to regulate a master transcription factor for osteogenesis, such as Runx2, as well as molecules in the Wnt or BMP signaling pathway, and control the balance between osteoblast and adipocyte differentiation. Here, we discuss recent advancement of the cell fate decision of MSCs by miRNAs and their targets. [BMB Reports 2015; 48(6): 319-323]

• Biomolecules & Therapeutics
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• 제13권4호
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• pp.199-206
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• 2005

Cell therapy (CT) is a group of techniques to treat human disorders by transplantation of cells which have been processed and propagated independent of the living body. Blood transfusion and bone marrow transplant have been the primary examples of cell therapy. With introduction of stem cell (SC) technologies, however, CT is perceived as the next generation of biologies to treat human diseases such as cancer, neurological diseases, and heart disease. Despite potential of cell therapy, insufficient guidelines have been implemented concerning safety test and regulation of cell therapy. This review addresses the safety issues to be resolved for the cell therapy, especially SC therapy, to be successfully utilized for clinical practice. Adequate donor cell screening must preceed to ensure safety in cell therapy. In terms of SC culture, controlled, standardized practices and procedures should be established. Further molecular studies should be done on SC development and differentiation to enhance safety level in cell therapy. Finally, animal model must be further installed to evaluate toxicity, new concepts, and proliferative potential of SC including alternative feeder layer of animal cells.

• 한국임상수의학회:학술대회논문집
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• 한국임상수의학회 2006년도 춘계학술대회
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• pp.109-109
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• 2006

• BMB Reports
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• 제51권4호
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• pp.194-199
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• 2018

Mesenchymal stem cells (MSCs) have shown great potential in treating bone deficiency. Human adipose-derived stem cells (HASCs) are multipotent progenitor cells with multi-lineage differentiation potential. Human amnion-derived mesenchymal stem cells (HAMSCs) are capable of promoting osteogenic differentiation of MSCs. In this study, we investigated the effect of HAMSCs on HASCs by a transwell co-culture system. HAMSCs promoted proliferation, osteogenic differentiation, angiogenic potential and adiponectin (APN) secretion of HASCs. Moreover, the positive effect of HAMSCs was significantly inhibited by U0126, a highly selective inhibitor of extracellular signaling-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) signaling pathway. These observations suggested that HAMSCs induced bone regeneration in HASCs via ERK1/2 MAPK signaling pathway.

• 생명과학회지
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• 제10권1호
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• pp.37-44
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• 2000

The mammary gland contains a subpopulation of epithelial cells with large proliferative potentials which are the likely targets for carcinogens. These clonogenic cells can proliferate and differentiate into functional glandular structures. Rat mammary epithelial cells (RMEC) were isolated and characterized in vitro. By flow cytometry of RMEC stained with fluorescein isothiocyanate-peanut agglutinin(PNA) and phycoerythrin anti-Thy-1.1 monoclonal antibody, it was possible to four cell subpopulations from 7-8 week old F344 female rat mammary glands: cells negative to both reagents (B-), PNA-positive cells (PNA+), Thy-1.1-positive cells (Thy-1.1+), and cells positive to both reagents (B+). When single PNA+ cells were isolated and cultured in Matrigel with irradiated (∼50 Gray) 3T3 fibroblast feeder layer, they gave rise to multicellular clonal structures of three types: alveolar, foamy alveolar, and squamous colonies. The developed structures were similar to the mammary glands in vivo. These results suggest that some of PNA+ cells possesses many of the characteristics of multipotent clonogenic stem-like cells.