Transplantation of vascular cells derived from human embryonic stem cells contributes to vascular regeneration after stroke in mice

<p>Abstract</p> <p>Background</p> <p>We previously demonstrated that vascular endothelial growth factor receptor type 2 (VEGF-R2)-positive cells induced from mouse embryonic stem (ES) cells can differentiate into both endothelial cells (ECs) and mural cells (MCs) and these vascular cells construct blood vessel structures in vitro. Recently, we have also established a method for the large-scale expansion of ECs and MCs derived from human ES cells. We examined the potential of vascular cells derived from human ES cells to contribute to vascular regeneration and to provide therapeutic benefit for the ischemic brain.</p> <p>Methods</p> <p>Phosphate buffered saline, human peripheral blood mononuclear cells (hMNCs), ECs-, MCs-, or the mixture of ECs and MCs derived from human ES cells were intra-arterially transplanted into mice after transient middle cerebral artery occlusion (MCAo).</p> <p>Results</p> <p>Transplanted ECs were successfully incorporated into host capillaries and MCs were distributed in the areas surrounding endothelial tubes. The cerebral blood flow and the vascular density in the ischemic striatum on day 28 after MCAo had significantly improved in ECs-, MCs- and ECs+MCs-transplanted mice compared to that of mice injected with saline or transplanted with hMNCs. Moreover, compared to saline-injected or hMNC-transplanted mice, significant reduction of the infarct volume and of apoptosis as well as acceleration of neurological recovery were observed on day 28 after MCAo in the cell mixture-transplanted mice.</p> <p>Conclusion</p> <p>Transplantation of ECs and MCs derived from undifferentiated human ES cells have a potential to contribute to therapeutic vascular regeneration and consequently reduction of infarct area after stroke.</p

内臓脂肪蓄積を伴う血液透析患者の食事摂取及び身体活動状況

Visceral fat accumulation is a risk factor for various cardiovascular diseases. Chronic hemodialysis patients are at higher risk for cardiovascular diseases than normal people. However, little is known about the health guidelines for decreasing visceral fat accumulation in hemodialysis patients. This study aimed to study the relationships between visceral fat content, nutrient intake, and physical activity between hemodialysis patients with and without visceral fat accumulation. Another objective was to determine the lifestyle factors that led to accumulation of visceral fat in hemodialysis patients.This study investigated 31 chronic hemodialysis patients in a hospital. Each individual's visceral fat area (VFA) was measured by performing computed tomography. Energy and various nutrient intakes and levels of physical activity were determined by using a food frequency questionnaire (FFQ). In the subjects, 10 had visceral fat accumulation and 21 did not. The average VFA was 168.7±67.9 cm2 in the accumulation group and 53.1±26.2 cm2 in the non-accumulation group. There was no significant difference in energy intake between the accumulation group and the non-accumulation group. The intake of vitamin D was significantly higher and that of seaweed was significantly lower in the accumulation group. The VFA of the group having high physical activity (Level 3) was significantly lower compared with that of the group having low physical activity (Level 1). Therefore, we hypothesize that, in chronic hemodialysis patients, the volume of nutritional elements and foods, not energy intakes, and the level of physical activity, may be associated with visceral fat accumulation

Augmentation of Neovascularizaiton in Hindlimb Ischemia by Combined Transplantation of Human Embryonic Stem Cells-Derived Endothelial and Mural Cells

BACKGROUND: We demonstrated that mouse embryonic stem (ES) cells-derived vascular endothelial growth factor receptor-2 (VEGF-R2) positive cells could differentiate into both endothelial cells (EC) and mural cells (MC), and termed them as vascular progenitor cells (VPC). Recently, we have established a method to expand monkey and human ES cells-derived VPC with the proper differentiation stage in a large quantity. Here we investigated the therapeutic potential of human VPC-derived EC and MC for vascular regeneration. METHODS AND RESULTS: After the expansion of human VPC-derived vascular cells, we transplanted these cells to nude mice with hindlimb ischemia. The blood flow recovery and capillary density in ischemic hindlimbs were significantly improved in human VPC-derived EC-transplanted mice, compared to human peripheral and umbilical cord blood-derived endothelial progenitor cells (pEPC and uEPC) transplanted mice. The combined transplantation of human VPC-derived EC and MC synergistically improved blood flow of ischemic hindlimbs remarkably, compared to the single cell transplantations. Transplanted VPC-derived vascular cells were effectively incorporated into host circulating vessels as EC and MC to maintain long-term vascular integrity. CONCLUSIONS: Our findings suggest that the combined transplantation of human ES cells-derived EC and MC can be used as a new promising strategy for therapeutic vascular regeneration in patients with tissue ischemia

インスリン テイコウセイ カイゼンザイ チアゾリジン ユウドウタイ ノ ケッカン キノウ エ ノ コウカ ニ カンスル ケンキュウ

京都大学0048新制・論文博士博士(医学)乙第12014号論医博第1920号新制||医||952(附属図書館)UT51-2007-H569京都大学大学院医学研究科内科系専攻(主査)教授 稲垣 暢也, 教授 野間 昭典, 教授 乾 賢一学位規則第4条第2項該当Doctor of Medical ScienceKyoto UniversityDA

Potential usefulness of 75-g oral glucose tolerance test using the flash glucose monitoring system in a comprehensive medical examination

目的：本研究では，人間ドック健診におけるフラッシュグルコースモニタリングシステム（FGM）を用いた75 g 経口ブドウ糖負荷試験（OGTT）の有用性を検討することを目的とした。方法：人間ドック健診を受診した健常ボランティア64 名を対象に，FGM（FreeStyle リブレPro®）センサーを装着して75 g OGTT を実施した。静脈血漿血糖値（PG）は60 分ごとに計3 回，FGM による間質液グルコース濃度（FGM-IG）は15 分ごとに計9 回測定し，PG とFGM-IG の関連を検討した。結果：PG とFGM-IG との間に有意な正の相関を認めた。FGM の精度を評価するコンセンサスエラーグリッド解析の結果，99.5 % の測定値が臨床的に利用可能とされる範囲内に該当し，平均絶対的相対的差異は13.7％であった。糖負荷前のFGM-IG はPG と比較して有意に低値であった。対象者64 名中60 名のOGTT において，PG とFGM-IG による判定が一致した。15 分ごとのFGM-IG の測定によって，60 分ごとのPG を用いた通常のOGTT では評価できないグルコース変動を捉えることが可能であった。結論：簡便かつ侵襲少なくグルコース濃度を測定できるFGM は，75 g OGTT において有用である可能性が示唆された

Sirt1 plays an important role in mediating greater functionality of human ES/iPS-derived vascular endothelial cells.

OBJECTIVE: We previously succeeded in inducing and isolating vascular endothelial cells (ECs) from both human embryonic stem (ES) and induced pluripotent stem (iPS) cells. Here, we compared the functionality of human adult ECs (HAECs), human ES-derived ECs (ESECs) and human iPS-derived ECs (iPSECs). METHODS AND RESULTS: We compared the cell proliferative potential, potential for migration, and tolerance to oxidative stress. ESECs were significantly superior to HAECs in all of these cell functions. The cell functions of iPSECs were comparable to those of ESECSs and also superior to HAECs. We then analyzed the gene expressions of HAECs, ESECs and iPSECs, and observed that the expression level of Sirt1, a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase, is higher in ESECs and iPSECs than in HAECs. The inhibition of Sirt1 with a Sirt1-specific inhibitor and siRNA antagonized these differences between the three types of cells. CONCLUSIONS: Sirt1 plays a key role in the high cellular function of ESECs and iPSECs. Although further in vivo investigations are required, this study initially demonstrated the potential of ESECs and iPSECs as the cell source for regenerative medicine, and also showed the potential of ES cells as a useful tool for elucidating the molecular mechanism of cell aging