Cell-Based therapy for traumatic brain injury

Abstract

Traumatic brain injury is a major economic burden to hospitals in terms of emergency department visits, hospitalizations, and utilization of intensive care units. Current guidelines for the management of severe traumatic brain injuries are primarily supportive, with an emphasis on surveillance (i.e. intracranial pressure) and preventive measures to reduce morbidity and mortality. There are no direct effective therapies available. Over the last fifteen years, pre-clinical studies in regenerative medicine utilizing cell-based therapy have generated enthusiasm as a possible treatment option for traumatic brain injury. In these studies, stem cells and progenitor cells were shown to migrate into the injured brain and proliferate, exerting protective effects through possible cell replacement, gene and protein transfer, and release of anti-inflammatory and growth factors. In this work, we reviewed the pathophysiological mechanisms of traumatic brain injury, the biological rationale for using stem cells and progenitor cells, and the results of clinical trials using cell-based therapy for traumatic brain injury. Although the benefits of cell-based therapy have been clearly demonstrated in pre-clinical studies, some questions remain regarding the biological mechanisms of repair and safety, dose, route and timing of cell delivery, which ultimately will determine its optimal clinical use.

Traumatic Brain Injury: Current Treatment Strategies and Future Endeavors

“…It has been revealed that enhancing neurogenesis, angiogenesis, and immunoregulation by secreting chemokine and growth factors are involved in the functional recovery induced by stem cell/progenitor cellbased interventions. [96][97][98][99] Several clinical trials in cell-based treatment for TBI recovery have demonstrated safety of this therapeutic approach. 100,101 However, the administration route, dose, and time window still remain controversial.…”

“…99,101,102 The administration dose of MSCs ranges from 0.1 to 20 million cells per kg body weight. 96 The approaches of lateral ventricle and intravenous injection have been utilized. 96 The timing for MSC transplantation in experimental animal models has been intensively studied within 24 h after TBI.…”

“…109 In animal models, the number of cells for transplantation ranges from 0.15 to 25 million cells per kg body weight. 96 The most common delivery method used for NSC transplantation is stereotactic injection to the brain. Although the timing for transplantation ranges from immediately after TBI to a few weeks later, [110][111][112] Shear et al 113 reported that NSC transplantation at 2 d after TBI showed better outcome than at 2 wk after TBI.…”

One Step at a Time, Stem Cell Therapy for Traumatic Brain Injury Needs Two More Breakthroughs

“…1,[23][24][25] Several preclinical studies have evaluated the efficacy of rodent neural precursor cells in TBI rodent models. 22,[26][27][28][29][30] The culturing NSCs in vitro started as an attempt to grow multipotent embryonic cortical tissue (the word neural stem cells was not yet coined) and successfully accomplished in 1989 at the University of Miami. 31 This work evolved when Martin Raff, a Canadian born Boston neurologist decided to move to England and chose to leave the United States (US) than fight in Vietnam War and to pursue immunology.…”

Evaluation of parametric response mapping to assess therapeutic response to human mesenchymal stem cells after experimental stroke

“…To this end, there is a strong interest in the potential of cell transplantation. 2,3 Among the cell populations currently available, human mesenchymal stem cells (hMSCs), derived from bone marrow, seem to have definite therapeutic potential due to their low immunogenicity under either autologous or allogeneic conditions, [3][4][5] although potential complications including cell clotting and cell-induced microembolism might impair their therapeutic safety and efficacy. 6 Their responses to the particular pathological microenvironments of cerebral ischemia make hMSCs exert multiple therapeutic effects at various sites and times within the stroke lesion by preventing neural cell death and improving neurological function.…”