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学位論文 |
学位
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Chin, Shunfu ; Furukawa, Ken-Ichi ; Ono, Atsushi ; Asari, Toru ; Harada, Yoshifumi ; Wada, Kanichiro ; Tanaka, Toshihiro ; Inaba, Wataru ; Mizukami, Hiroki ; Motomura, Shigeru ; Yagihashi, Soroku ; Ishibashi, Yasuyuki
概要:
Mesenchymal stem cells (MSCs) have been isolated from various tissues and used for elucidating the pathogenesis of numer
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ous diseases. In our previous in vitro study, we showed the existence of MSCs in human spinal ligaments and hypothesized that these MSCs contributed to the pathogenesis of ossification of spinal ligaments. The purpose of this study was to use immunohistochemical techniques to analyze the localization of MSCs in ossified human spinal ligaments in situ. Ossified (OLF) or non-ossified ligamentum flavum (non-OLF) samples from the thoracic vertebra were obtained from patients who had undergone posterior spinal surgery. Serial sections were prepared from paraffin-embedded samples, and double immunofluorescence staining was performed using antibodies against markers for MSCs (CD73, CD90 and CD105), endothelial cells (CD31), pericytes (α-smooth muscle actin), and chondrocytes (S100). Immunolocalization of MSCs was observed in the perivascular area and collagenous matrix in spinal ligaments. Markers for MSCs and pericytes were co-expressed in the perivascular area. Compared with non-OLF, OLF had a large amount of neovascularization in the fragmented ligament matrix, and a high accumulation of MSCs around blood vessels. The prevalence of MSCs in OLF within collagenous matrix was significantly higher than that in non-OLF. Chondrocytes near the ossification front in OLF also presented expression of MSC markers. MSCs may contribute to the ectopic ossification process of OLF through endochondral ossification.
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| 2.
学位論文 |
学位
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Kamata, Kosuke ; Mizukami, Hiroki ; Inaba, Wataru ; Tsuboi, Kentaro ; Tateishi, Yoshinori ; Yoshida, Taro ; Yagihashi, Soroku
概要:
Aims: Islet amyloid is a hallmark in type 2 diabetic subjects, but its implication in clinical features and development of islet pathology is still unclear.Methods: From 118 autopsy cases with type 2 diabetes, 26 cases with
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islet amyloid deposition (DA+) were selected. Twenty diabetic subjects without obvious amyloid deposition (DA ) matched for the age and diabetes duration and 20 non-diabetic subjects (ND) served for comparison. We examined the severity of amyloid deposition and its relationships with population of endocrine cells, expression of cell damage markers or macrophage infiltration. Correlation of clinical profile with islet pathology was also sought on the subset of the investigated patients.Results: b-Cell volume density was nearly 40% less in DA+ and 20% less in DA when compared to ND. Severity of amyloid deposition correlated with reduced volume densities of b-cell and a-cell, and increased body mass index (BMI), but not with duration of diabetes, age or HbA1c. Amyloid-rich islets contained an increased number of macrophages mixed with b-cells with oxidative stress-related DNA damage, characterized by gH2AX expression, and suppressed (pro)insulin mRNA expression.Conclusions: In Japanese type 2 diabetic patients, islet amyloid was more common with severe b-cell loss and high BMI, associated with macrophage infiltration.
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