Stem Cell Therapy for Spinal Cord Injuries

Stem cell-based therapies are an emerging branch of medicine with the purpose of restoring tissue function for patients with serious injuries, such as a spinal cord injury. As a result, scientists and engineers are increasing research efforts in the field of regenerative medicine. Due to the delicate nature of stem cells, producing the large quantity required for a successful therapy has proved challenging. In recent years, research has shown the potential of stem cell-based therapies, and thus there is a need for the commercialization of these treatments. The proposed facility targets the demand for spinal cord injury treatments and can support production for both clinical trials and a commercial release. Bioreactors designed specifically for the culture and growth of stem cells have flexibility in their ability to support different stem cell lines for various therapies. Small reactors in parallel can easily adapt to changes in production size. This process also takes advantage of the best options currently available for purification and preservation to maximize the product yield. Due to the strict regulations set in place by the FDA and lack of adequate funding, there is an untapped market for stem cell therapies for spinal cord injuries. Approximately 250,000 people in the United States suffer from spinal cord injuries, varying in severity, and this patient base increases at a rate of 12,000 new injuries every year (“Spinal Cord Injury Facts and Figures”, 2009). Future markets include expansion into Europe and Asia. There are two steps to this proposal: the upstream process and the downstream process. The upstream process includes the scale-up, differentiation, and purification of human embryonic stem cells; the downstream process consists of the scale-up of neurons for injection. The upstream process will be built initially and yield enough cells for clinical trials, without incurring the capital costs of building the entire plant. Upon success of the clinical trials, the downstream process will be built for maximum production. The profitability of this proposal is based on running 26 batches a year at 1.02x1010 cells per batch or 2.66x1011 cells per year. By targeting 5,000 patients, two percent of the current market, and charging $45,000 per dose, a profitable profile can be created. Assuming 50$961,892,600, and 242.81% respectively. Using a 50% production capacity allows for higher profit margins upon expansion. The proposed plan will meet the need of this growing market

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

MULTIFUNCTIONAL CHEMICAL CROSS-LINKERS FOR QUANTIFYING AND VISUALIZING INTRACELLULAR PROCESSES

Chemical cross-linkers have proven valuable for a diversity of biological applications such as protein enrichment, nanoparticle surface functionalization, and conjugate-based drug delivery. Two valuable subclasses of cross-linkers include cleavable and heteromultifunctional linkers. The introduction of cleavage sites within a linker is important for drug delivery applications, as it enables programmable and spatiotemporal release of tethered molecules or therapeutic cargo. Heteromultifunctional linkers that allow the orthogonal attachment of multiple biomolecules or chemical moieties are important for the synthesis of heterovalent ligands and molecular probes. Due to synthetic limitations, a vast majority of cleavable linkers have been limited to a single cleavage site. Traditional approaches for synthesizing heteromultifunctional linkers are limited to three functional groups and lack the functional diversity to allow for orthogonal cleavage via nonenzymatic cues. Further, approaches that utilize natural amino acids and peptidyl scaffolds are sensitive to proteolysis in the biological environment. An emerging paradigm in polymer chemistry is the synthesis of sequence-defined polymers. Oligothioetheramides (oligoTEAs), a subset of sequence-defined polymers, have recently been reported by our research group. The oligoTEA synthesis approach utilizes an orthogonally reactive N-allylacrylamide monomer, which can undergo alternating photoinitiated thiol-ene “click” reactions and phosphine-catalyzed thiol-Michael additions. Aside from their facile synthesis, oligoTEAs have several benefits including the incorporation of a diverse panel of pendant and backbone functionalities. Furthermore, oligoTEAs are stable to proteolytic degradation and as such are stable in the biological environment. We have leveraged the iterative nature of oligoTEA synthesis to address many of the limitations of heteromultifunctional cross-linker synthesis. Herein, I will describe the development of oligoTEAs as a platform for synthesizing cleavable heteromultifunctional cross-linkers. We have taken this class of cross-linkers and applied it towards quantifying the intracellular processing of stimuli-responsive drug carriers. In combination with a kinetic model, we have extracted the rate constant for intracellular disulfide bond degradation in the HER2 receptor endocytic pathway. In collaboration with the Paszek group, we have also used our synthesis platform to design probes to visualize the glycocalyx via expansion microscopy. These probes selectively modify metabolically-labelled cell surface glycans via bioorthogonal “click” chemistry. Taken together, these works highlight the utility of oligoTEAs as a platform to design heteromultifunctional cross-linkers for a range of biological applications