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T rauma and its secondary complications are leading causes of morbidity and mortality worldwide. Despite the large number of individuals affected by traumatic injury, there are few therapeutic options to decrease morbidity, mortality and improve outcomes. In June 2016, the National Academies of Science Engineering and Medicine published their findings on the trauma care system in the United States. Trauma was reported to be one of the leading causes of morbidity and mortality in the United States; however, the field as a whole receives significantly less support for prevention, research and the development of novel interventions compared to cancer, heart disease, HIV, and a number of other human diseases. Traumatic injury is responsible for creating a tremendous burden to society and results in a greater number of years of potential life lost (YPLL) than any other human disease. Novel lifesaving therapies in trauma and critical care are clearly an unmet medical need. Victims of trauma who survive the initial injury often suffer from multiple secondary consequences including wound infections, acute lung injury/acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), neurocognitive dysfunction after traumatic brain injury (TBI), and paralysis after spinal cord injury (SCI). Aside from supportive care, there are few if any interventions that significantly reduce the morbidity and mortality of these conditions. This is an area of medicine with limited therapeutic options and unlimited scope for advancement. Relevant to combat casualty care, it is clear that many of the wounded warriors who have suffered battlefield injuries are in dire need of reparative and regenerative therapies after they survive the initial injury. The same is true of civilian trauma. An emerging area of investigation that has generated considerable attention and interest over the past 10 years is the use of cellular therapies (CT) to prevent damage and promote repair of injured tissue in trauma and critical care applications. Cell-based therapies provide a viable approach to improving outcomes in critically injured patients. The utilization of CT in trauma actually began long before endeavors in stem cell therapies or regenerative medicine, with the transfusion of whole blood in exsanguinating patients. Before the concept of stem cell therapies and prior to component-based blood transfusion, transfusion of whole blood was indeed the first cell therapy to be clinically utilized. The first trauma patient to receive a blood transfusion in the United States dates back to the Civil War (1861–1865), where hemorrhage caused three-fourths of the deaths. In recent years, the field of CT and regenerative medicine has grown and generated global excitement over the potential to address many different types of diseases. In trauma and critical care applications, CT is being investigated for both the acute and chronic phases of injury. Although the field is still in its early stages of development, animal and human studies demonstrate the promise of CT for trauma-induced conditions such as TBI, SCI, organ failure (ARDS, AKI), orthopedic trauma, burns, and ischemia/reperfusion insults. This supplement in the journal TRANSFUSION selects a group of papers that are focused on speaker topics presented at the biannual conference Cellular Therapies in Trauma and Critical Care Medicine (CTTACC). This supplement was generated from the third CTTACC conference that took place in San Francisco, California, in 2017. The primary goal and laser focus of CTTACC is to accelerate and advance the translation of CT and novel blood products, two of the most rapidly developing areas in transfusion medicine, to trauma patients. The topics selected for this supplement are focused on the translation of novel therapeutics, novel blood products, and CT to trauma and critical care patients. Both areas of investigation have similar challenges in research, development, and translation to patients, and are key future directions for transfusion medicine as a field. In the first paper, Ness and Gehring outline the history and challenges of whole blood transfusion versus blood component–based transfusion. There has recently been an