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

A novel lipoprotein (a) lowering drug, D-47, decreases neointima thickening after vascular injury

Although Lp(a) have been thought to be a cardiovascular risk factor, it is unclear whether lowering Lp(a) levels reduces the risk of cardiovascular diseases. No pharmacological agents which selectively reduce serum Lp(a) levels, and Lp(a) is present in primate but absent in common laboratory animals such as mice and pigs. In the present study we used transgenic mice of human Lp(a) and tested effect a novel Lp(a) lowering drug D-47 on neointima formation after vascular injury. D-47 successfully decreased plasma levels of Lp(a) and possibly inhibited neointima formation in Lp(a) transgenic mice. The results indicate that we can modulate plasma Lp(a) levels by pharmacologic agents and inhibit atherogenic properties of Lp(a) by reducing plasma levels of Lp(a)

CRYSTAL GROWTH OF RARE EARTH COMPOUNDS IN CLOSED SYSTEM

Remarkable improvements have been made on the crystal growth of rare earth pnictides and chalchogenides by the development of new growth technique and the construction of several new equipments for the crystal growth such as electron beam welding system of tungsten crucible provided with large glove box and vacuum HF furnace. This system has really worked on obtaining excellent quality of single crystals and made easier to explore unknown materials of rare earth compounds. Interesting and attractive physical properties of these compounds were obtained from the crystals produced by this system and contributed to extend a new scope of the heavy Fermion physics

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

Comparison of Visual Evoked Potential Components between Laser and Cathod-Ray Tubes Stimulation in Healthy Human Subjects

We studied the differences in latency and amplitude between the laser stimulated visual evoked potentials (VEPs) and the cathode-ray tubes (CRTs) stimulated VEPs to estimate the risk of inducing photosensitive epilepsy by laser displays. Twenty healthy subjects were recruited for the study. Red and blue light stimulations were flashed in 1, 7.5 and 15Hz. The latency of P1, N1, P2 and N2 in 1 Hz stimulation revealed no significant difference by a paired t test between laser and CRT stimulation. The peak-to-peak amplitude was significantly smaller with red or blue laser stimulation than with red or blue CRT stimulation, for PI-N1 and N1-P2 at 7.5Hz stimulation, and for N1-P2 and P2-N2 at 15Hz stimulation. We therefore postulate that laser does not produce more excitability to occipital cerebral cortex than CRT does. There was no evidence to say that laser stimulation is more dangerous as the risk of inducing photosensitive epilepsy than conventional CRT stimulation

Overview of the Nishinoshima comprehensive scientific research project, in 2021

小笠原諸島の西之島は2013年から2021年までに5度の噴火で元の陸地は全域が溶岩に覆われ、火山灰が堆積して大地がリセットされた。この島は太平洋上に孤立し、最寄の陸地から130kmも隔離された無人島であることから、海洋島における生態系の一次遷移を人為的影響のない状態で観察できる世界に例のない場所と言える。生物、地質及び火山活動における網羅的な分野の調査を噴火直後から実施することで、火山島の形成過程、噴火による生物相への影響、新たな遷移の開始時点の状況等を把握することができる。そこで、西之島の自然環境の最新情報を記録して科学的価値を評価するための総合学術調査が企画され、2019年調査に続き、2021年7月、9月の2度にわたり、モニタリング調査を実施した。新規に海域調査を実施したほか、UAVやAUVを活用した新規の調査も取り入れた。本調査は環境省とともに、東京大学及び日本放送協会との連携により行われている。調査の実施に当たっては、火山活動が活発な島における安全管理には十分配慮したほか、調査による人為的な影響を最小限に抑えるため、外来生物の侵入を防止するための検疫を徹底した。Nishinoshima Island in the Ogasawara Islands has erupted five times between 2013 and 2021. The entire original land area was covered by lava, as well as by thick deposits of volcanic ash that have reset the land surface. As an uninhabited island isolated in the Pacific Ocean and 130 km apart from the nearest land, it offers an unique opportunity to observe primary succession on an oceanic island without human impacts. Thus, it is important to conduct comprehensive field surveys on its biota, geology and volcanic activities immediately after the eruption in order to understand the formation process of the volcanic island, the impact of the eruption on the biota, and the situations at the start of primary succession. Therefore, a comprehensive scientific survey was planned to record the latest information on the nature of Nishinoshima Island and assess its scientific value. It was conducted twice, in July and September 2021, following the 2019 survey. This is the first survey of marine biota around Nishinoshima Island, and UAVs and AUVs were also actively used to conduct the survey safely during volcanic activity. The survey was carried out in collaboration with the Ministry of the Environment, the University of Tokyo and the Japan Broadcasting Corporation (NHK). In carrying out the survey, sufficient attention was paid to safety management on the volcanically active island, and quarantine was also strictly enforced as a measure to prevent the invasion of alien species in order to eliminate any human impact of the survey.departmental bulletin pape