• Molecules and Cells
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• 제40권6호
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• pp.386-392
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• 2017

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 characteristics 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, ${\alpha}-smooth$ muscle actin, platelet-derived growth factor receptor ${\beta}$, 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 $SDF-1{\alpha}$ 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 diseases.

• Molecules and Cells
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• 제40권6호
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• pp.434-439
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• 2017

Gestational diabetes mellitus (GDM), one of the common metabolic disorders of pregnancy, leads to functional alterations in various cells including stem cells as well as some abnormalities in fetal development. Perivascular stem cells (PVCs) have gained more attention in recent years, for the treatment of various diseases. However, the effect of GDM on PVC function has not been investigated. In our study, we isolated PVCs from umbilical cord of normal pregnant women and GDM patients and compared their phenotypes and function. There is no significant difference in phenotypic expression, response to bFGF exposure and adipogenic differentiation capacity between normal (N)-PVCs and GDM-PVCs. However, when compared with N-PVCs, early passage GDM-PVCs displayed decreased initial rates of cell yield and proliferation as well as a reduced ability to promote wound closure. These results suggest that maternal metabolic dysregulation during gestation can alter the function of endogenous multipotent stem cells, which may impact their therapeutic effectiveness.

• 한국발생생물학회지:발생과생식
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• 제21권1호
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• pp.11-18
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• 2017

Potassium channels, the largest group of pore proteins, selectively regulate the flow of potassium ($K^+$) ions across cell membranes. The activity and expression of $K^+$ channels are critical for the maintenance of normal functions in vessels and neurons, and for the regulation of cell differentiation and maturation. However, their role and expression in stem cells have been poorly understood. In this study, we isolated perivascular stem cells (PVCs) from human umbilical cords and investigated the expression patterns of big-conductance $Ca^{2+}$-activated $K^+$ ($BK_{Ca}$) and voltage-dependent $K^+$ ($K_v$) channels using the reverse transcription polymerase chain reaction. We also examined the effect of high glucose (HG, 25 mM) on expression levels of $BK_{Ca}$ and $K_v$ channels in PVCs. $K_{Ca}1.1$, $K_{Ca}{\beta}_3$, $K_v1.3$, $K_v3.2$, and $K_v6.1$ were detected in undifferentiated PVCs. In addition, HG treatment increased the amounts of $BK_{Ca}{\beta}_{3a}$, $BK_{Ca}{\beta}_4$, $K_v1.3$, $K_v1.6$, and $K_v6.1$ transcripts. These results suggested that ion channels may have important functions in the growth and differentiation of PVCs, which could be influenced by HG exposure.

• Molecules and Cells
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• 제39권11호
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• pp.790-796
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• 2016

Dental pulp is a highly vascularized tissue requiring adequate blood supply for successful regeneration. In this study, we investigated the functional role of stem cells from human exfoliated deciduous teeth (SHEDs) as a perivascular source for in vivo formation of vessel-like structures. Primarily isolated SHEDs showed mesenchymal stem cell (MSC)-like characteristics including the expression of surface antigens and in vitro osteogenic and adipogenic differentiation potentials. Moreover, SHEDs were positive for NG2, ${\alpha}$-smooth muscle actin (SMA), platelet-derived growth factor receptor beta ($PDGFR{\beta}$), and CD146 as pericyte markers. To prove feasibility of SHEDs as perivascular source, SHEDs were transplanted into immunodeficient mouse using Matrigel with or without human umbilical vein endothelial cells (HUVECs). Transplantation of SHEDs alone or HUVECs alone resulted in no formation of vessel-like structures with enough red blood cells. However, when SHEDs and HUVECs were transplanted together, extensive vessel-like structures were formed. The presence of murine erythrocytes within lumens suggested the formation of anastomoses between newly formed vessel-like structures in Matrigel plug and the host circulatory system. To understand underlying mechanisms of in vivo angiogenesis, the expression of angiogenic cytokine and chemokine, their receptors, and MMPs was compared between SHEDs and HUVECs. SHEDs showed higher expression of1VEGF, SDF-$1{\alpha}$, and $PDGFR{\beta}$ than HUVECs. On the contrary, HUVECs showed higher expression of VEGF receptors, CXCR4, and PDGF-BB than SHEDs. This differential expression pattern suggested reciprocal interactions between SHEDs and HUVECs and their involvement during in vivo angiogenesis. In conclusion, SHEDs could be a feasible source of perivascular cells for in vivo angiogenesis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5579-5587
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• 2013

Research indicates that a small population of cancer cells is highly tumorigenic, endowed with the capacity for self-renewal, and has the ability to differentiate into cells that constitute the bulk of tumors. These cells are considered the "drivers" of the tumorigenic process in some tumor types, and have been named cancer stem cells (CSC). Epithelial-mesenchymal transition (EMT) appears to be involved in the process leading to the acquisition of stemness by epithelial tumor cells. Through this process, cells acquire an invasive phenotype that may contribute to tumor recurrence and metastasis. CSC have been identified in human head and neck squamous cell carcinomas (HNSCC) using markers such as CD133 and CD44 expression, and aldehyde dehydrogenase (ALDH) activity. Head and neck cancer stem cells reside primarily in perivascular niches in the invasive fronts where endothelial-cell initiated events contribute to their survival and function. Clinically, CSC enrichment has been shown to be enhanced in recurrent disease, treatment failure and metastasis. CSC represent a novel target of study given their slow growth and innate mechanisms conferring treatment resistance. Further understanding of their unique phenotype may reveal potential molecular targets to improve therapeutic and survival outcomes in patients with HNSCC. Here, we discuss the state-of-the-knowledge on the pathobiology of cancer stem cells, with a focus on the impact of these cells on head and neck tumor progression, metastasis and recurrence due to treatment failure.

• 생명과학회지
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• 제29권5호
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• pp.530-536
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• 2019

교모세포종은 형질 전환된 신경 교세포로부터 유래한 악성 종양이다. 교모세포종의 치료는 외과적 수술을 포함한 약물 및 방사선 치료를 통해 진행된다. 그러나 이러한 치료 과정이 환자의 예후에 크게 기여하지 못하는 실정이다. 교모세포종 치료의 어려움 중 하나로 뇌종양줄기세포의 존재를 들 수 있다. 주요하게 proneural (PN) 아형과 mesenchymal (MES) 아형으로 나누어지는 뇌종양줄기세포는 교모세포종의 발달, 유지 및 항암 치료 후 재발의 원인이 되는 암세포로 이해되고 있다. 본 연구에서는 PN 아형 뇌종양줄기세포들이 특정 사이토카인에 선택적으로 MES 아형으로 전이가 될 수 있다는 것에 중점을 두고 실험을 진행하였다. PN 아형 뇌종양줄기세포 중 GSC11 세포는 $TNF-{\alpha}$ 사이토카인에 의해, 그리고 GSC23 세포는 $TGF-{\beta}1$ 사이토카인에 노출이 될 때 MES 아형 뇌종양줄기세포의 표지 인자인 CD44의 발현 증가가 관찰되었다. 또한, Ivy Glioblastoma Atlas Project (Ivy GAP) 데이터 베이스를 통해, $TNF-{\alpha}$와 $TGF-{\beta}1$은 종양미세환경을 구성하는 요소 중 각각 괴사 부위와 미세혈관 주위에서 높은 발현을 보임을 확인하였다. 따라서 본 연구 결과는 PN 아형의 뇌종양줄기세포가 특정 종양미세환경에서 조절되는 다양한 종류의 사이토카인 신호에 의해 MES 아형으로의 전이가 결정될 수 있다는 가능성을 시사한다.

• 한국발생생물학회지:발생과생식
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• 제24권3호
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• pp.197-205
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• 2020

Diabetes mellitus is a common heterogeneous metabolic disorder, characterized by deposition of extracellular matrix, oxidative stress, and vascular dysfunction, thereby leading to gradual loss of function in multiple organs. However, little attention has been paid to gene expression changes in the lung under hyperglycemic conditions. In this study, we found that diabetes inuced histological changes in the lung of streptozotocin-induced diabetic mice. Global gene expression profiling revealed a set of genes that are up- and down-regulated in the lung of diabetic mice. Among these, expression of Amigo2, Adrb2, and Zbtb16 were confirmed at the transcript level to correlate significantly with hyperglycemia in the lung. We further evaluated the effect of human umbilical cord-derived perivascular stem cells (PVCs) on these gene expression in the lung of diabetic mice. Our results show that administration of PVC-conditioned medium significantly suppressed Amig2, Adrb2, and Zbtb16 upregulation in these mice, suggesting that these genes may be useful indicators of lung injury during hyperglycemia. Furthermore, PVCs offer a promising alternative cell therapy for treating diabetic complications via regulation of gene expression.