Human Retinal Progenitor Cell Transplantation Preserves Vision

Cell transplantation is a potential therapeutic strategy for retinal degenerative diseases involving the loss of photoreceptors. However, it faces challenges to clinical translation due to safety concerns and a limited supply of cells. Human retinal progenitor cells (hRPCs) from fetal neural retina are expandable in vitro and maintain an undifferentiated state. This study aimed to investigate the therapeutic potential of hRPCs transplanted into a Royal College of Surgeons (RCS) rat model of retinal degeneration. At 12 weeks, optokinetic response showed that hRPC-grafted eyes had significantly superior visual acuity compared with vehicle-treated eyes. Histological evaluation of outer nuclear layer (ONL) characteristics such as ONL thickness, spread distance, and cell count demonstrated a significantly greater preservation of the ONL in hRPC-treated eyes compared with both vehicle-treated and control eyes. The transplanted hRPCs arrested visual decline over time in the RCS rat and rescued retinal morphology, demonstrating their potential as a therapy for retinal diseases. We suggest that the preservation of visual acuity was likely achieved through host photoreceptor rescue. We found that hRPC transplantation into the subretinal space of RCS rats was well tolerated, with no adverse effects such as tumor formation noted at 12 weeks after treatment.     

A system identification approach for developing model predictive controllers of antibody quality attributes in cell culture processes

As the biopharmaceutical industry evolves to include more diverse protein formats and processes, more robust control of Critical Quality Attributes (CQAs) is needed to maintain processing flexibility without compromising quality. Active control of CQAs has been demonstrated using model predictive control techniques, which allow development of processes which are robust against disturbances associated with raw material variability and other potentially flexible operating conditions. Wide adoption of model predictive control in biopharmaceutical cell culture processes has been hampered, however, in part due to the large amount of data and expertise required to make a predictive model of controlled CQAs, a requirement for model predictive control. Here we developed a highly automated, perfusion apparatus to systematically and efficiently generate predictive models using application of system identification approaches. We successfully created a predictive model of %galactosylation using data obtained by manipulating galactose concentration in the perfusion apparatus in serialized step change experiments. We then demonstrated the use of the model in a model predictive controller in a simulated control scenario to successfully achieve a %galactosylation set point in a simulated fed‐batch culture. The automated model identification approach demonstrated here can potentially be generalized to many CQAs, and could be a more efficient, faster, and highly automated alternative to batch experiments for developing predictive models in cell culture processes, and allow the wider adoption of model predictive control in biopharmaceutical processes. © 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 33:1647–1661, 2017     

Pharmacological characterization of 3H-LSD binding sites in mouse brain in vivo.

In mice receiving i.v. low doses of ³H-LSD the accumulation of radioactivity in brain appears to reflect a selective binding to high affinity sites as indicated by the heterogenous regional distribution (paralleling that observed in in vitro binding studies) and by the saturable character of the process (ED₅₀ around 30μg.kg^?1 in cerebral cortex).The identity of the binding sites was assessed in various regions by administration of agonists or antagonists of different neurotransmitters. In cortex specific accumulation of ³H-LSD was easily prevented by administration of serotonin antagonists (cyproheptadine, methysergide, methiothepin) or by tryptamine derivatives (psilocin, psilocybin, dimethyltryptamine) and 5-hydroxytryptophan + pargyline. Among neuroleptics some prevented ³H-LSD binding (spiperone, haloperidol) whereas 1mg.kg^?1 pimozide was ineffective. In addition a large variety of agents (adrenergic, cholinergic, morphine) were ineffective. These data suggest a selective binding to cortical serotonin receptors.