Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

Genetical genomics of growth in a chicken model

Background: The genetics underlying body mass and growth are key to understanding a wide range of topics in biology, both evolutionary and developmental. Body mass and growth traits are affected by many genetic variants of small effect. This complicates genetic mapping of growth and body mass. Experimental intercrosses between individuals from divergent populations allows us to map naturally occurring genetic variants for selected traits, such as body mass by linkage mapping. By simultaneously measuring traits and intermediary molecular phenotypes, such as gene expression, one can use integrative genomics to search for potential causative genes. Results: In this study, we use linkage mapping approach to map growth traits (N = 471) and liver gene expression (N = 130) in an advanced intercross of wild Red Junglefowl and domestic White Leghorn layer chickens. We find 16 loci for growth traits, and 1463 loci for liver gene expression, as measured by microarrays. Of these, the genes TRAK1, OSBPL8, YEATS4, CEP55, and PIP4K2B are identified as strong candidates for growth loci in the chicken. We also show a high degree of sex-specific gene-regulation, with almost every gene expression locus exhibiting sex-interactions. Finally, several trans-regulatory hotspots were found, one of which coincides with a major growth locus. Conclusions: These findings not only serve to identify several strong candidates affecting growth, but also show how sex-specificity and local gene-regulation affect growth regulation in the chicken.Funding Agencies|Carl Tryggers Stiftelse; Swedish Research Council (VR); Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS); Linkoping University Neuro-network; European Research Council [GENEWELL 322206]</p

The Impact of Three Different Wash Solutions on Autotransfusion Products

Many blood conservation techniques and strategies have been implemented to aid in decreasing the use of allogenic blood utilization during pediatric cardiothoracic surgery. Use of techniques, such as acute normovolemic hemodilution, retrograde autologous prime, venous autologous prime, and autotransfuion, may lead to a decrease in the need for allogenic blood products. Autotransfusion has become a standard of care for all cardiothoracic surgical procedures requiring cardiopulmonary bypass (CPB). Although widely used, there is still debate over which wash solution will produce the most physiologically normal autotransfusion product. Pediatric patients can be at a higher risk for electrolyte imbalance intraoperatively and postoperatively. In an attempt to minimize this, we sought out to evaluate three different wash solutions and how they would affect the final autotransfusion product. This comparison consisted of three wash solutions; .9% sodium chloride, Normosol-R™, and Plasma-Lyte A. Based on the evaluation of all wash solutions, Plasma-Lyte A produced the most physiological normal final autotransfusion product in regards to electrolytes

Bloodless Repair for a 3.6 Kilogram Transposition of the Great Arteries with Jehovah’s Witness Faith

Achieving pediatric cardiac surgery using cardiopulmonary bypass (CPB) without allogeneic blood transfusion is challenging. There are many clinical and economic factors that point to the importance of avoiding blood transfusions. In some instances, honoring patients or parents beliefs may be the reason for avoiding blood transfusions. For example, patients or parents of the Jehovah’s Witness faith refuse blood transfusion based on their religious beliefs. Over the last decade, our institution has seen a steady increase in our pediatric Jehovah’s Witness patient population. Caring for these patients have allowed us to develop specific protocols that enable us to safely provide bloodless CPB in all of our patient populations. The success of such an approach to minimize the need for blood transfusions should not start in the operating room; it must include the preoperative period and the postoperative care by the critical care team in the cardiac intensive care unit (CICU). A multidisciplinary team approach has to be in place with clear communication between the cardiologist, anesthesiologist, cardiac surgeon, perfusionist, and the cardiac intensivist. We present a case of a 7 day old male (3.6 kg) with a preoperative diagnosis of Transposition of the Great Arteries and intact ventricular septum who underwent an arterial switch procedure without the transfusion of any blood products throughout his entire hospital stay