Katherine Cameron

Recombinant Laminins Drive the Differentiation and Self-Organization of hESC-Derived Hepatocytes

Summary Stem cell-derived somatic cells represent an unlimited resource for basic and translational science. Although promising, there are significant hurdles that must be overcome. Our focus is on the generation of the major cell type of the human liver, the hepatocyte. Current protocols produce variable populations of hepatocytes that are the product of using undefined components in the differentiation process. This serves as a significant barrier to scale-up and application. To tackle this issue, we designed a defined differentiation process using recombinant laminin substrates to provide instruction. We demonstrate efficient hepatocyte specification, cell organization, and significant improvements in cell function and phenotype. This is driven in part by the suppression of unfavorable gene regulatory networks that control cell proliferation and migration, pluripotent stem cell self-renewal, and fibroblast and colon specification. We believe that this represents a significant advance, moving stem cell-based hepatocytes closer toward biomedical application.

High-Speed Integrated Visible Light Communication System: Device Constraints and Design Considerations

Visible light communications (VLC) has the potential to play a major part in future smart home and next generation communication networks. There is significant ongoing work to increase the achievable data rates using VLC, to standardize it and integrate it within existing network infrastructures. The future of VLC systems depends on the ability to fabricate low cost transceiver components and to realize the promise of high data rates. This paper reports the design and fabrication of integrated transmitter and receiver components. The transmitter uses a two dimensional individually addressable array of micro light emitting diodes (μLEDs) and the receiver uses an integrated photodiode array fabricated in a CMOS technology. A preliminary result of a MIMO system implementation operating at a data rate of 1 Gbps is demonstrated. This paper also highlights the challenges in achieving highly parallel data communication along with the possible bottlenecks in integrated approaches.

Spike timing dependent plasticity (STDP) can ameliorate process variations in neuromorphic VLSI

A transient-detecting very large scale integration (VLSI) pixel is described, suitable for use in a visual-processing, depth-recovery algorithm based upon spike timing. A small array of pixels is coupled to an adaptive system, based upon spike timing dependent plasticity (STDP), that aims to reduce the effect of VLSI process variations on the algorithms performance. Results from 0.35 /spl mu/m CMOS temporal differentiating pixels and STDP circuits show that the system is capable of adapting to substantially reduce the effects of process variations without interrupting the algorithms natural processes. The concept is generic to all spike timing driven processing algorithms in a VLSI.

Modulating Innate Immunity Improves Hepatitis C Virus Infection and Replication in Stem Cell-Derived Hepatocytes

Summary In this study, human embryonic stem cell-derived hepatocytes (hESC-Heps) were investigated for their ability to support hepatitis C virus (HCV) infection and replication. hESC-Heps were capable of supporting the full viral life cycle, including the release of infectious virions. Although supportive, hESC-Hep viral infection levels were not as great as those observed in Huh7 cells. We reasoned that innate immune responses in hESC-Heps may lead to the low level of infection and replication. Upon further investigation, we identified a strong type III interferon response in hESC-Heps that was triggered by HCV. Interestingly, specific inhibition of the JAK/STAT signaling pathway led to an increase in HCV infection and replication in hESC-Heps. Of note, the interferon response was not evident in Huh7 cells. In summary, we have established a robust cell-based system that allows the in-depth study of virus-host interactions in vitro.

Directed osteogenic differentiation of human mesenchymal stem/precursor cells on silicate substituted calcium phosphate.

Insufficient, underactive, or inappropriate osteoblast function results in serious clinical conditions such as osteoporosis, osteogenesis imperfecta and fracture nonunion and therefore the control of osteogenesis is a medical priority. In vitro mesenchymal stem cells (MSCs) can be directed to form osteoblasts through the addition of soluble factors such as β-glycerophosphate, ascorbic acid, and dexamethasone; however this is unlikely to be practical in the clinical setting. An alternative approach would be to use a scaffold or matrix engineered to provide cues for differentiation without the need for soluble factors. Here we describe studies using Silicate-substituted calcium phosphate (Si-CaP) and unmodified hydroxyapatite (HA) to test whether these materials are capable of promoting osteogenic differentiation of MSCs in the absence of soluble factors. Si-CaP supported attachment and proliferation of MSCs and induced osteogenesis to a greater extent than HA, as evidenced through upregulation of the osteoblast-related genes: Runx2 (1.2 fold), Col1a1 (2 fold), Pth1r (1.5 fold), and Bglap (1.7 fold) Dmp1 (1.1 fold), respectively. Osteogenic-associated proteins, alkaline phosphatase (1.4 fold), RUNX2, COL1A1, and BGLAP, were also upregulated and there was an increased production of mineralized bone matrix (1.75 fold), as detected by the Von Kossa Assay. These data indicate that inorganic substrates are capable of directing the differentiation programme of stem cells in the absence of known chemical drivers and therefore may provide the basis for bone repair in the clinical setting.

A neuromorphic depth-from-motion vision model with STDP adaptation

We propose a simplified depth-from-motion vision model based on leaky integrate-and-fire (LIF) neurons for edge detection and two-dimensional depth recovery. In the model, every LIF neuron is able to detect the irradiance edges passing through its receptive field in an optical flow field, and respond to the detection by firing a spike when the neurons firing criterion is satisfied. If a neuron fires a spike, the time-of-travel of the spike-associated edge is transferred as the prediction information to the next synapse-linked neuron to determine its state. Correlations between input spikes and their timing thus encode depth in the visual field. The adaptation of synapses mediated by spike-timing-dependent plasticity is used to improve the algorithms robustness against inaccuracy caused by spurious edge propagation. The algorithm is characterized on both artificial and real image sequences. The implementation of the algorithm in analog very large scale integrated (aVLSI) circuitry is also discussed.

Polymer Supported Directed Differentiation Reveals a Unique Gene Signature Predicting Stable Hepatocyte Performance

In theory, pluripotent stem cells can give rise to all somatic cell types found in the human body. The ability to generate renewable sources of human cells has enormous potential to improve human health and wealth. One major obstacle to the routine deployment of stem cell-derived cells is their instability in culture. To tackle this issue a synthetic polymer surface is used.

Neuromorphic Control of Stepping Pattern Generation: A Dynamic Model With Analog Circuit Implementation

Animals such as stick insects can adaptively walk on complex terrains by dynamically adjusting their stepping motion patterns. Inspired by the coupled Matsuoka and resonate-and-fire neuron models, we present a nonlinear oscillation model as the neuromorphic central pattern generator (CPG) for rhythmic stepping pattern generation. This dynamic model can also be used to actuate the motoneurons on a leg joint with adjustable driving frequencies and duty cycles by changing a few of the model parameters while operating such that different stepping patterns can be generated. A novel mixed-signal integrated circuit design of this dynamic model is subsequently implemented, which, although simplified, shares the equivalent output performance in terms of the adjustable frequency and duty cycle. Three identical CPG models being used to drive three joints can make an arthropod leg of three degrees of freedom. With appropriate initial circuit parameter settings, and thus suitable phase lags among joints, the leg is expected to walk on a complex terrain with adaptive steps. The adaptation is associated with the circuit parameters mediated both by the higher level nervous system and the lower level sensory signals. The model is realized using a 0.3- complementary metal-oxide-semiconductor process and the results are reported.

Pluripotent stem cell derived hepatocytes: using materials to define cellular differentiation and tissue engineering

Pluripotent stem cell derived liver cells (hepatocytes) represent a promising alternative to primary tissue for biological and clinical applications.

Minimizing the Effect of Process Mismatch in a Neuromorphic System Using Spike-Timing-Dependent Adaptation

This paper investigates whether spike-timing-dependent plasticity (STDP) can minimize the effect of mismatch within the context of a depth-from-motion algorithm. To improve noise rejection, this algorithm contains a spike prediction element, whose performance is degraded by analog very large scale integration (VLSI) mismatch. The error between the actual spike arrival time and the prediction is used as the input to an STDP circuit, to improve future predictions. Before STDP adaptation, the error reflects the degree of mismatch within the prediction circuitry. After STDP adaptation, the error indicates to what extent the adaptive circuitry can minimize the effect of transistor mismatch. The circuitry is tested with static and varying prediction times and chip results are presented. The effect of noisy spikes is also investigated. Under all conditions the STDP adaptation is shown to improve performance.