관상동맥 질환에서 SDF-1α의 농도

김보영,박용규,박형서,노상필,정승현,이유선,이정우,이재환,최시완,정진옥,성인환 충남대학교 의과대학 의학연구소 2003 충남의대잡지 Vol.30 No.1

Atherosclerosis is now viewed as an inflammatory disease of the vascular system. Expression of several chemokines, including monocyte chemoattractant protein(MCP)-1, MCP-4, RANTES(regulated on activation normal T-cell expressed and secreted), and interleukin-8(IL-8) are increased in human atherosclerotic plaques compared with normal vessels. They are involved in the pathogenesis of atherosclerosis and plaque rupture by activating and directing leukocytes into the atherosclerotic lesions. However, some are involved in homeostatic functions such as normal leukocyte traffic and growth regulation. SDF-la is a multi-functional cytokine that is involved in myelogenesis, hematopoiesis, angiogenesis and injured gastric mucosal regeneration in the gastric ulcer patient. SDF-la is recently shown to be highly expressed in atherosclerotic plaques and a potent platelet agonist. At least in high concentrations, SDF-la may mediate antiinflammatory and matrix stabilizing effects in unstable angina. Many studies are going on to know the function of SDF-la in coronary artery diseases. I investigated the difference of the plasma level of SDF-la between control group and coronary artery disease group. Total 75 subjects were enrolled. The diagnosis of coronary artery disease was confirmed in all patients by coronary angiography. Control subjects in this study were confirmed normal by coronary angiography. Clinical profile and risk factors were also reviewed. Control subjects in this study were 27 (M=10, F=17). Plasma for the study was collected before the angiography and centrifuged. SDF-la analysis was performed by ELISA. Plasma level of SDF-la is significantly increased in patients with stable angina(n=20) and unstable angina group(n=28) compared with healthy control group(n=27). the risk factors do not influence the plasma level of SDF-la in coronary artery diseases. In this study, plasma level of SDF-la is increased in patients with stable angina and unstable angina groups compared with healthy control group(P<0.05). the risk factors do not influence the plasma level of SDF-la in coronary artery diseases.

Stromal-cell-derived Factor 1-α Promotes Tumor Progression in Colorectal Cancer

박세준,안태성,조성우,김창진,정동준,손명원,배상호,신응진,이문수,김창호,백무준 대한대장항문학회 2012 Annals of Coloproctolgy Vol.28 No.1

Purpose: Although stromal-cell-derived factor (SDF)-1α is suggested to be involved in tumorigenicity and tumor angiogenesis,the clinicopathological significance of its expression in colorectal cancers is not fully understood. We examined SDF-1α expression in colorectal cancers and investigated its relationship to clinicopathological features such as tumor staging, lymph-node metastasis, vascular invasion (VI), lymphatic invasion (LI) and neural invasion (NI). Methods: Specimens of 83 primary colorectal cancers were examined immunohistochemically, and the relationships between clinicopathological features and SDF-1α expression were analyzed. To compare the expressions between the normal colon tissue and colorectal cancer tissues, we performed Western blot analyses. Results: According to the Western blot analyses, SDF-1α was more highly expressed in colorectal carcinoma tissues than in normal colonic mucosa (20/21). According to the immunohistochemical stain, SDF-1α was associated with nodal status,distant metastasis, tumor staging, VI and LI. SDF-1α expression had a significant prognostic value for overall survival. Kaplan-Meier plots of survival in patients with high SDF-1α showed that high SDF-1α expression was associated with a shorter overall survival. However, no association was found between SDF-1α expression and other pathologic or clinical variables, including age, gender, degree of differentiation, and presence of perineural invasion. Conclusion: The expression of SDF-1α might be associated with tumor progression in colorectal cancer. Inhibition of SDF-1α could be a therapeutic option in colorectal cancer patients.

림프구의 부착과 이동을 조절하는 세포간 부착 분자 ICAM-1의 세포질 영역에 관한 연구

서검석(Geom-Seog Seo),최민규(Minkyu Choi),오현미(Hyun-Mee Oh),이무형(Moo Hyung Lee),이강민(Kang-Min Lee),나용호(Yong-Ho Nah),전창덕(Chang-Duk Jun) 대한해부학회 2005 Anatomy & Cell Biology Vol.38 No.1

ICAM-1의 세포질 영역이 림프구 세포의 부착과 이동을 조절할 수 있는 지를 알아보기 위해, 세포질 영역이 삭제된 여러 형태의 mutant type ICAM-1_GFP를 제작한 후, SDF-1α 케모카인에 의한 T 림프구의 부착과 이동을 연구하였다. 세포질 영역이 없거나, 세포질 영역 중 α-actinin 결합자리가 없는 mutant type ICAM-1_GFP의 경우, actin cytoskeleton과 결합할 수 없어서 wild type과 상당히 다른 세포막 발현형태를 나타내었다. T 림프구의 표면 인테그린이 SDF-1α에 의해 활성화되면, 활성화된 LFA-1과 ICAM-1의 결합에 의해 T 림프구가 ICAM-1 발현세포에 부착하게 되는데, 이 과정에서 ICAM-1의 세포질 영역은 그다지 역할을 하지 않는 것으로 나타났다. 림프구 부착 후, 림프구를 감싸기 위한 막 돌기가 형성되는 것을 볼 수 있는데, 세포질 영역이 없는 mutant type ICAM-1_GFP는 wild type에 비해 막 돌기를 잘 형성하지 못하는 것을 관찰할 수 있었다. 이러한 결과들은 ICAM-1의 세포질 영역이 림프구 세포의 부착과정에서 역할을 하는 것이 아니라, 부착 후 막 돌기가 형성되는 과정에서 역할을 한다는 것을 말해주며, 이 후 내피세포를 통한 림프구 세포의 이동 시에도 ICAM-1의 세포질 영역이 중요할 것으로 생각된다. Intercellular adhesion molecule-1 (ICAM-1) has been shown to enhance leukocyte adhesion, thereby inducing migration through blood endothelial cells. However, the molecular event during the process of adhesion is largely unknown. To examine the role of ICAM-1 cytoplasmic domain in SDF-1 α-induced T lymphocyte migration and adhesion, mutant human ICAM-1 molecules were expressed in COS-7 cell line. COS-7 cells expressing ICAM- 1_GFP mutant without α-actinin revealed no association with the actin cytoskeleton, while wild-type ICAM-1 showed clear association with the actin, as observed by confocal microscopy, suggesting that actinin binding motif in the cytoplasmic domain of ICAM-1 is important for the proper localization of ICAM-1 on the cell membrane. However, based on adhesion assay, we found that the cytoplasmic domain of ICAM-1 is not essential for the binding of lymphocytes which were activated by SDF-1α. On the other hand, ICAM-1-mediated receptor-ligand clustering event was significantly inhibited in the cells expressing ICAM-1 mutants without α-actinin or whole cytoplasmic domain. Taken together, these results suggest that ICAM-1 cytoplasmic domain is not essential for the adhesion but important for the ligand-receptor-mediated membrane projection of endothelial cells before trans-endothelial migration of lymphocytes.

Bioreducible Polymer Micelles Based on Acid-Degradable Poly(ethylene glycol)-poly(amino ketal) Enhance the Stromal Cell-Derived Factor-1α Gene Transfection Efficacy and Therapeutic Angiogenesis of Human Adipose-Derived Stem Cells

Lee, Tae-Jin,Shim, Min Suk,Yu, Taekyung,Choi, Kyunghee,Kim, Dong-Ik,Lee, Soo-Hong,Bhang, Suk Ho MDPI 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.2

<P>Adipose-derived stem cells (ADSCs) have the potential to treat ischemic diseases. In general, ADSCs facilitate angiogenesis by secreting various pro-angiogenic growth factors. However, transplanted ADSCs have a low therapeutic efficacy in ischemic tissues due to their poor engraftment and low viability. Stromal cell-derived factor-1α (SDF-1α) improves the survival rate of stem cells transplanted into ischemic regions. In this study, we developed acid-degradable poly(ethylene glycol)-poly(amino ketal) (PEG-PAK)-based micelles for efficient intracellular delivery of <I>SDF-1α</I> plasmid DNA. The <I>SDF-1α gene</I> was successfully delivered into human ADSCs (hADSCs) using PEG-PAK micelles. Transfection of <I>SDF-1α</I> increased <I>SDF-1α</I>, vascular endothelial growth factor, and basic fibroblast growth factor gene expression and decreased apoptotic activity in hADSCs cultured under hypoxic conditions in comparison with conventional gene transfection using polyethylenimine. <I>SDF-1α</I>-transfected hADSCs also showed significantly increased <I>SDF-1α</I> and VEGF expression together with reduced apoptotic activity at 4 weeks after transplantation into mouse ischemic hindlimbs. Consequently, these cells improved angiogenesis in ischemic hindlimb regions. These PEG-PAK micelles may lead to the development of a novel therapeutic modality for ischemic diseases based on an acid-degradable polymer specialized for gene delivery.</P>

Acid-degradable poly(ethylene glycol)-poly(amino ketal) for enhancing gene transfection efficacy and therapeutic angiogenesis of stem cells

박정환,방석호 한국공업화학회 2018 한국공업화학회 연구논문 초록집 Vol.2018 No.0

Adipose-derived stem cells (ADSCs) have the potential to treat ischemic diseases. However, transplanted ADSCs have a low therapeutic efficacy in ischemic tissues due to their poor engraftment and low viability. In this study, we developed acid-degradable poly(ethylene glycol)-poly (amino ketal) (PEG-PAK)-based micelles for efficient intracellular delivery of stromal cell-derived factor-1α (SDF-1α) plasmid DNA. The SDF-1α gene was successfully delivered into human ADSCs (hADSCs) using PEG-PAK micelles. Transfection of SDF-1α increased SDF-1α, vascular endothelial growth factor, and basic fibroblast growth factor gene expression and decreased apoptotic activity in hADSCs cultured under hypoxic conditions in comparison with conventional gene transfection using polyethylenimine. Consequently, these cells improved angiogenesis in ischemic hindlimb regions.

The Chemokine SDF-1α Suppresses Fibronectin-mediated In Vitro Lymphocytes Adhesion

Wang ZhengTao,Ji LiLi,Sheng YuChen 한국분자세포생물학회 2006 Molecules and cells Vol.22 No.3

The Significance of SDF-1α-CXCR4 Axis in in vivo Angiogenic Ability of Human Periodontal Ligament Stem Cells

배윤경,김지혜,이재천,서병무,주경민,이진,남현 한국분자세포생물학회 2017 Molecules and cells Vol.40 No.6

Periodontal ligament stem cells (PDLSCs) are multipotent stem cells derived from periodontium and have mesenchymal stem cell (MSC)-like characteristics. Recently, the perivascular region was recognized as the developmental origin of MSCs, which suggests the in vivo angiogenic potential of PDLSCs. In this study, we investigated whether PDLSCs could be a potential source of perivascular cells, which could contribute to in vivo angiogenesis. PDLSCs exhibited typical MSC-like charac-teristics such as the expression pattern of surface markers (CD29, CD44, CD73, and CD105) and differentiation potentials (osteogenic and adipogenic differentiation). Moreover, PDLSCs expressed perivascular cell markers such as NG2, α-smooth muscle actin, platelet-derived growth factor receptor β, and CD146. We conducted an in vivo Matrigel plug assay to confirm the in vivo angiogenic potential of PDLSCs. We could not observe significant vessel-like structures with PDLSCs alone or human umbilical vein endothelial cells (HUVECs) alone at day 7 after injection. However, when PDLSCs and HUVECs were co-injected, there were vessel-like structures containing red blood cells in the lumens, which suggested that anastomosis occurred between newly formed vessels and host circulatory system. To block the SDF-1α and CXCR4 axis between PDLSCs and HUVECs, AMD3100, a CXCR4 antagonist, was added into the Matrigel plug. After day 3 and day 7 after injection, there were no significant vessel-like structures. In conclusion, we demonstrated the perivascular characteristics of PDLSCs and their contribution to in vivo angiogenesis, which might imply potential application of PDLSCs into the neovascularization of tissue engineering and vascular dis-eases.

Design Considerations of Iron-Based Nanoclusters for Noninvasive Tracking of Mesenchymal Stem Cell Homing

Huang, Xinglu,Zhang, Fan,Wang, Yu,Sun, Xiaolian,Choi, Ki Young,Liu, Dingbin,Choi, Jin-sil,Shin, Tae-Hyun,Cheon, Jinwoo,Niu, Gang,Chen, Xiaoyuan American Chemical Society 2014 ACS NANO Vol.8 No.5

<P/><P>Stem-cell-based therapies have attracted considerable interest in regenerative medicine and oncological research. However, a major limitation of systemic delivery of stem cells is the low homing efficiency to the target site. Here, we report a serendipitous finding that various iron-based magnetic nanoparticles (MNPs) actively augment chemokine receptor CXCR4 expression of bone-marrow-derived mesenchymal stem cells (MSCs). On the basis of this observation, we designed an iron-based nanocluster that can effectively label MSCs, improve cell homing efficiency, and track the fate of the cells <I>in vivo</I>. Using this nanocluster, the labeled MSCs were accurately monitored by magnetic resonance imaging and improved the homing to both traumatic brain injury and glioblastoma models as compared to unlabeled MSCs. Our findings provide a simple and safe method for imaging and targeted delivery of stem cells and extend the potential applications of iron-based MNPs in regenerative medicine and oncology.</P>