Abstract
Mesenchymal stromal cells (MSCs) are widely used in preclinical models of traumatic brain injury (TBI). Results are promising in terms of neurological improvement but are hampered by wide variability in treatment responses. We made a systematic review and meta-analysis: (1) to assess the quality of evidence for MSC treatment in TBI rodent models; (2) to determine the effect size of MSCs on sensorimotor function, cognitive function, and anatomical damage; (3) to identify MSC-related and protocol-related variables associated with greater efficacy; (4) to understand whether MSC manipulations boost therapeutic efficacy. The meta-analysis included 80 studies. After TBI, MSCs improved sensorimotor and cognitive deficits and reduced anatomical damage. Stratified meta-analysis on sensorimotor outcome showed similar efficacy for different MSC sources and for syngeneic or xenogenic transplants. Efficacy was greater when MSCs were delivered in the first-week post-injury, and when implanted directly into the lesion cavity. The greatest effect size was for cells embedded in matrices or for MSC-derivatives. MSC therapy is effective in preclinical TBI models, improving sensorimotor, cognitive, and anatomical outcomes, with large effect sizes. These findings support clinical studies in TBI.
Highlights
Every year, worldwide, about 69 million people suffer traumatic brain injury (TBI), about 13 million of them moderate to severe[1].Survivors often experience severe and persistent motor and cognitive deficits, resulting in a huge economic burden on society[2,3,4]
All Mesenchymal stromal cells (MSCs) modification groups presented publication bias for neurologic assessment and cognitive function but not for contusion volume. This meta-analysis investigated the effects of MSCs in preclinical models of TBI and found that they improved sensorimotor and cognitive functions as well as anatomical damage
Efficacy on sensorimotor outcomes was robust when analyzed in relation to MSC source and type of transplant, time of administration, delivery route, and doses (Fig. 8) as well as recipient species and multiple models of TBI
Summary
Worldwide, about 69 million people suffer traumatic brain injury (TBI), about 13 million of them moderate to severe[1].Survivors often experience severe and persistent motor and cognitive deficits, resulting in a huge economic burden on society[2,3,4]. Worldwide, about 69 million people suffer traumatic brain injury (TBI), about 13 million of them moderate to severe[1]. Mesenchymal stromal cells (MSCs) are multipotent progenitor cells first isolated from bone marrow[7], and subsequently from many other sources including adipose tissue and birth-related tissues (umbilical cord and umbilical cord blood, amniotic fluid, or placenta)[8]. MSCs are attractive candidates for cell therapy because of their ease of isolation and ex vivo expansion, their low immunogenicity, and high immunosuppressive activity[9]. Twenty years ago the first experimental study assessing MSC protective effects in TBI was published[10]. Other elements contributing to heterogeneity are represented by MSC modifications introduced to boost efficacy including the use of matrices[14,15], genetic manipulations[16,17], or in vitro preconditioning[18]. Cell-free approaches based on MSC bioactive factors (secretome or extracellular vesicles) have been tested[19]
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