Cellular Therapies in Trauma and Critical Care Medicine

Abstract

Trauma is a leading cause of death in both military and civilian populations worldwide. Although medical advances have improved the overall morbidity and mortality often associated with trauma, additional research and innovative advancements in therapeutic interventions are needed to optimize patient outcomes. Cell-based therapies present a novel opportunity to improve trauma and critical care at both the acute and chronic phases that often follow injury. Although this field is still in its infancy, animal and human studies suggest that stem cells may hold great promise for the treatment of brain and spinal cord injuries, organ injuries, and extremity injuries such as those caused by orthopedic trauma, burns, and critical limb ischemia. However, barriers in the translation of cell therapies that include regulatory obstacles, challenges in manufacturing and clinical trial design, and a lack of funding are critical areas in need of development. In 2015, the Department of Defense Combat Casualty Care Research Program held a joint military–civilian meeting as part of its effort to inform the research community about this field and allow for effective planning and programmatic decisions regarding research and development. The objective of this article is to provide a “state of the science” review regarding cellular therapies in trauma and critical care, and to provide a foundation from which the potential of this emerging field can be harnessed to mitigate outcomes in critically ill trauma patients.

Human primary fibroblasts perform similarly to MSCs in assays used to evaluate MSC safety and potency

“…Based on their previously described immune modulatory and anti-inflammatory properties, stem or progenitor cells may be good therapeutic agents in the acute phase after injury. 1,2 Sequelae of the initial injury include inflammation, ischemia, and edema; modulation of the immune response to injury may mitigate further tissue damage. Because cell therapy agents also have angiogenic and wound-healing properties, benefits may extend beyond the acute injury.…”

“…Cellular therapeutics have the potential to benefit both military and civilian trauma patients. Based on their previously described immune modulatory and anti‐inflammatory properties, stem or progenitor cells may be good therapeutic agents in the acute phase after injury . Sequelae of the initial injury include inflammation, ischemia, and edema; modulation of the immune response to injury may mitigate further tissue damage.…”

Traumatic Penumbra: Opportunities for Neuroprotective and Neurorestorative Processes

“…Cellular therapies fall into two main categories of cell types: adult multipotent cells and pluripotent embryonic stem cells (ESCs). Adult multipotent cells, such as mesenchymal stem cells, multipotent adult progenitor cells (MAPCs), hematopoietic stem cells (HSCs), and bone marrow mononuclear cells (BMMNCs), have the capacity to generate a limited number of terminally differentiated cell types [168]. Cell-based therapies have been shown to improve outcomes in preclinical studies of trauma-related conditions via several mechanisms, which include: (i) production of soluble factors that regulate the exacerbated cell damage through anti-inflammatory and cell-protective effects (i.e., growth factors, cytokines, microvesicles, exosomes); (ii) replacement of lost cells by differentiating and integrating into the damaged tissue microenvironment; and (iii) stimulation of endogenous regeneration of the injured tissue [167].…”

Cellular therapies in trauma and critical care medicine: Looking towards the future

“…While research is advancing in multiple areas of clinical investigation, including orthopedic trauma and wound healing [5], we focus here on the areas of neurotrauma (TBI and SCI) and organ failure (ARDS).…”