Methods in molecular biology
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Composite tissue transplantation is an emerging new era in transplant medicine and has become a viable reconstructive option for patients with large and devastating tissue defects. Advances in microsurgical techniques, transplant immunology and the development of potent immunosuppressive agents have enabled the realization of such types of transplants. ⋯ However, despite the fact that surgical, immunological and functional results are highly encouraging, the need for long-term and high-dose immunosuppression to enable graft survival and to treat/reverse acute skin rejection episodes remains a pace-limiting obstacle towards wide spread application. In this chapter we review the history and development of this novel field, the functional and immunological outcomes based on the world experience, unique biological features of such transplants, mechanisms and treatment protocols for acute skin rejection, as well as novel concepts for immune modulation and tolerance induction.
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The isolation of embryonic stem cells (ESCs) has furthered our understanding of normal embryonic development and fueled the progression of stem cell derived therapies. However, the generation of ESCs requires the destruction of an embryo, making the use of these cells ethically controversial. In 2006 the Yamanaka group overcame this ethical controversy when they described a protocol whereby somatic cells could be dedifferentiated into a pluripotent state following the transduction of a four transcription factor cocktail. ⋯ The fast paced field of cellular reprogramming has recently produced protocols to generate iPSCs using non integrative techniques with an ever improving efficiency. These recent developments have brought us one step closer to developing a safe and efficient method to reprogram cells for clinical use. However, a lot of work is still needed before iPSCs can be implemented in a clinical setting.
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This chapter will outline strategies and ideas for the commercialization a promising wound healing technology discovered in an academic setting. This would include, but not limited to addressing topics such as intellectual property protection, funding, technology development, and regulatory aspects (i.e., navigating through the FDA).
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Complex, interrelated systems exist to maintain the fluidity of the blood in the vascular system while allowing for the rapid formation of a solid blood clot to prevent hemorrhaging subsequent to blood vessel injury. These interrelated systems are collectively referred to as haemostasis. The components involved in the haemostatic mechanism consist of vessel walls, platelets, coagulation factors, inhibitors, and the fibrinolytic system. ⋯ Once the fibrin clot is formed, the fibrinolytic system ensures that the clot is lysed so that it does not become a pathological complication. Taken together, the systems exist to balance each other and maintain order. The balance of coagulation and fibrinolysis keeps the haemostatic system functioning efficiently.
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Human and mouse alkaline phosphatases (AP) are encoded by a multigene family expressed ubiquitously in multiple tissues. Gene knockout (KO) findings have helped define some of the precise exocytic functions of individual isozymes in bone, teeth, the central nervous system, and in the gut. For instance, deficiency in tissue-nonspecific alkaline phosphatase (TNAP) in mice (Alpl (-/-) mice) and humans leads to hypophosphatasia (HPP), an inborn error of metabolism characterized by epileptic seizures in the most severe cases, caused by abnormal metabolism of pyridoxal-5'-phosphate (the predominant form of vitamin B6) and by hypomineralization of the skeleton and teeth featuring rickets and early loss of teeth in children or osteomalacia and dental problems in adults caused by accumulation of inorganic pyrophosphate (PPi). ⋯ Analogous to the role of IAP in the gut, TNAP expression in the liver may have a proactive role from bacterial endotoxin insult. Finally, more recent studies suggest that neuronal death in Alzheimer's disease may also be associated with TNAP function on certain brain-specific phosphoproteins. This review recounts the established roles of TNAP and IAP and briefly discusses new areas of investigation related to multisystemic functions of these isozymes.