Continuously tunable modulation scheme for homodyne detection and state tomography.

Homodyne detection is a common self-referenced technique to extract optical quadratures. Due to ubiquitous fluctuations, experiments measuring optical quadratures require homodyne angle control. Current homodyne angle locking techniques only provide high quality error signals in a span significantly smaller than π radians, the span required for full state tomography, leading to inevitable discontinuities during full tomography.

Human Hemangioblast-Derived Mesenchymal Stem Cells Promote Islet Engraftment in a Minimal Islet Mass Transplantation Model in Mice.

Islet transplantation can restore glycemic control in patients with type 1 diabetes. Using this procedure, the early stages of engraftment are often crucial to long-term islet function, and outcomes are not always successful. Numerous studies have shown that mesenchymal stem cells (MSCs) facilitate islet graft function.

Laser power stabilization via radiation pressure.

This Letter reports the experimental realization of a novel, to the best of our knowledge, active power stabilization scheme in which laser power fluctuations are sensed via the radiation pressure driven motion they induce on a movable mirror. The mirror position and its fluctuations were determined by means of a weak auxiliary laser beam and a Michelson interferometer, which formed the in-loop sensor of the power stabilization feedback control system. This sensing technique exploits a nondemolition measurement, which can result in higher sensitivity for power fluctuations than direct, and hence destructive, detection.

Next-generation stem cells - ushering in a new era of cell-based therapies.

Naturally occurring stem cells isolated from humans have been used therapeutically for decades. This has primarily involved the transplantation of primary cells such as haematopoietic and mesenchymal stem cells and, more recently, derivatives of pluripotent stem cells. However, the advent of cell-engineering approaches is ushering in a new generation of stem cell-based therapies, greatly expanding their therapeutic utility.

Engineering universal cells that evade immune detection.

The prospect of transplanting cells and tissues without the risk of immune rejection or the need for powerful immunosuppressive drugs is the 'holy grail' of transplantation medicine. Now, with the advent of pluripotent stem cells, CRISPR-Cas9 and other gene-editing technologies, the race to create 'off-the-shelf' donor cells that are invisible to the immune system ('universal cells') has started. One important approach for creating such cells involves the manipulation of genes required for immune recognition, in particular HLA class I and II proteins.

Measurement of quantum back action in the audio band at room temperature.

Quantum mechanics places a fundamental limit on the precision of continuous measurements. The Heisenberg uncertainty principle dictates that as the precision of a measurement of an observable (for example, position) increases, back action creates increased uncertainty in the conjugate variable (for example, momentum). In interferometric gravitational-wave detectors, higher laser powers reduce the position uncertainty created by shot noise (the photon-counting error caused by the quantum nature of the laser) but necessarily do so at the expense of back action in the form of quantum radiation pressure noise (QRPN).

Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration.

Purpose: Transplantation of human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells offers the potential for benefit in macular degeneration. Previous trials have reported improved visual acuity (VA), but lacked detailed analysis of retinal structure and function in the treated area.

Design: Phase 1/2 open-label dose-escalation trial to evaluate safety and potential efficacy (clinicaltrials.

Human Embryonic Stem Cell-Derived Mesenchymal Stromal Cells Decrease the Development of Severe Experimental Autoimmune Uveitis in B10.RIII Mice.

Purpose: We investigated the effect of exogenously administered human embryonic stem cell-derived mesenchymal stromal cells (hESC-MSCs) in experimental autoimmune uveitis (EAU) in B10.RIII mice, a murine model of severe uveitis.

Methods: B10.

Retinal vascular injuries and intravitreal human embryonic stem cell-derived haemangioblasts.

Objective: To investigate whether intravitreally applied haemangioblasts (HB) derived from human embryonic stem cells (hESCs) are helpful for the repair of vascular damage caused in animals by an oxygen-induced retinopathy (OIR), by an induced diabetic retinopathy (DR) or by an induced retinal ischaemia with subsequent reperfusion.

Methods: Human embryonic stem cell-derived HBs were transplanted intravitreally into C57BL/6J mice (OIR model), into male Wistar rats with an induced DR and into male Wistar rats undergoing induced retinal ischaemia with subsequent reperfusion. Control groups of animals received an intravitreal injection of endothelial cells (ECs) or phosphate-buffered saline (PBS).

Pluripotent stem cells: the last 10 years.

Pluripotent stem cells (PSCs) can differentiate into virtually any cell type in the body, making them attractive for both regenerative medicine and drug discovery. Over the past 10 years, technological advances and innovative platforms have yielded first-in-man PSC-based clinical trials and opened up new approaches for disease modeling and drug development. Induced PSCs have become the foremost alternative to embryonic stem cells and accelerated the development of disease-in-a-dish models.

First Measurements of High Frequency Cross-Spectra from a Pair of Large Michelson Interferometers.

Measurements are reported of the cross-correlation of spectra of differential position signals from the Fermilab Holometer, a pair of colocated 39 m long, high power Michelson interferometers with flat broadband frequency response in the MHz range. The instrument obtains sensitivity to high frequency correlated signals far exceeding any previous measurement in a broad frequency band extending beyond the 3.8 MHz inverse light-crossing time of the apparatus.

Function of human pluripotent stem cell-derived photoreceptor progenitors in blind mice.

Photoreceptor degeneration due to retinitis pigmentosa (RP) is a primary cause of inherited retinal blindness. Photoreceptor cell-replacement may hold the potential for repair in a completely degenerate retina by reinstating light sensitive cells to form connections that relay information to downstream retinal layers. This study assessed the therapeutic potential of photoreceptor progenitors derived from human embryonic and induced pluripotent stem cells (ESCs and iPSCs) using a protocol that is suitable for future clinical trials.

Efficient Generation of Human Embryonic Stem Cell-Derived Corneal Endothelial Cells by Directed Differentiation.

Aim: To generate human embryonic stem cell derived corneal endothelial cells (hESC-CECs) for transplantation in patients with corneal endothelial dystrophies.

Materials And Methods: Feeder-free hESC-CECs were generated by a directed differentiation protocol. hESC-CECs were characterized by morphology, expression of corneal endothelial markers, and microarray analysis of gene expression.

Human embryonic stem cell-derived mesenchymal cells preserve kidney function and extend lifespan in NZB/W F1 mouse model of lupus nephritis.

Adult tissue-derived mesenchymal stromal cells (MSCs) are showing promise in clinical trials for systemic lupus erythematosus (SLE). However, the inability to manufacture large quantities of functional cells from a single donor as well as donor-dependent variability in quality limits their clinical utility. Human embryonic stem cell (hESC)-derived MSCs are an alternative to adult MSCs that can circumvent issues regarding scalability and consistent quality due to their derivation from a renewable starting material.

Current status of pluripotent stem cells: moving the first therapies to the clinic.

Pluripotent stem cells (PSCs) hold great promise for drug discovery and regenerative medicine owing to their ability to differentiate into any cell type in the body. After more than three decades of research, including delays due to the potential tumorigenicity of PSCs and inefficiencies in differentiation methods, the field is at a turning point, with a number of clinical trials across the globe now testing PSC-derived products in humans. Ocular diseases dominate these first-in-man trials, and Phase l/ll results are showing promising safety data as well as possible efficacy.

Treatment of perianal fistulas with human embryonic stem cell-derived mesenchymal stem cells: a canine model of human fistulizing Crohn's disease.

Aim: To evaluate the safety and efficacy of intralesional injection of human embryonic stem cell (hESC)-derived mesenchymal stem/stromal cells (MSCs) in canine anal furunculosis dogs.

Materials & Methods: Dogs naturally develop an immune-mediated disease called canine anal furunculosis, which shares many features with human fistulizing Crohn's disease.

Results: The hESC-MSCs were well tolerated and 1 month postinjection, accompanied by reduced serum levels of IL-2 and IL-6, two inflammatory cytokines associated with Crohn's disease.

Treatment of macular degeneration using embryonic stem cell-derived retinal pigment epithelium: preliminary results in Asian patients.

Embryonic stem cells hold great promise for various diseases because of their unlimited capacity for self-renewal and ability to differentiate into any cell type in the body. However, despite over 3 decades of research, there have been no reports on the safety and potential efficacy of pluripotent stem cell progeny in Asian patients with any disease. Here, we report the safety and tolerability of subretinal transplantation of human embryonic-stem-cell (hESC)-derived retinal pigment epithelium in four Asian patients: two with dry age-related macular degeneration and two with Stargardt macular dystrophy.

Platelet bioreactor-on-a-chip.

Platelet transfusions total >2.17 million apheresis-equivalent units per year in the United States and are derived entirely from human donors, despite clinically significant immunogenicity, associated risk of sepsis, and inventory shortages due to high demand and 5-day shelf life. To take advantage of known physiological drivers of thrombopoiesis, we have developed a microfluidic human platelet bioreactor that recapitulates bone marrow stiffness, extracellular matrix composition,micro-channel size, hemodynamic vascular shear stress, and endothelial cell contacts, and it supports high-resolution live-cell microscopy and quantification of platelet production.

Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: follow-up of two open-label phase 1/2 studies.

Background: Since they were first derived more than three decades ago, embryonic stem cells have been proposed as a source of replacement cells in regenerative medicine, but their plasticity and unlimited capacity for self-renewal raises concerns about their safety, including tumour formation ability, potential immune rejection, and the risk of differentiating into unwanted cell types. We report the medium-term to long-term safety of cells derived from human embryonic stem cells (hESC) transplanted into patients.

Methods: In the USA, two prospective phase 1/2 studies were done to assess the primary endpoints safety and tolerability of subretinal transplantation of hESC-derived retinal pigment epithelium in nine patients with Stargardt's macular dystrophy (age >18 years) and nine with atrophic age-related macular degeneration (age >55 years).

Scalable generation of universal platelets from human induced pluripotent stem cells.

Human induced pluripotent stem cells (iPSCs) provide a potentially replenishable source for the production of transfusable platelets. Here, we describe a method to generate megakaryocytes (MKs) and functional platelets from iPSCs in a scalable manner under serum/feeder-free conditions. The method also permits the cryopreservation of MK progenitors, enabling a rapid "surge" capacity when large numbers of platelets are needed.

Human ESC-derived MSCs outperform bone marrow MSCs in the treatment of an EAE model of multiple sclerosis.

Current therapies for multiple sclerosis (MS) are largely palliative, not curative. Mesenchymal stem cells (MSCs) harbor regenerative and immunosuppressive functions, indicating a potential therapy for MS, yet the variability and low potency of MSCs from adult sources hinder their therapeutic potential. MSCs derived from human embryonic stem cells (hES-MSCs) may be better suited for clinical treatment of MS because of their unlimited and stable supply.