Systematic review and meta-analysis of preclinical studies testing mesenchymal stromal cells for traumatic brain injury

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.

Neuroprotection by the noble gases argon and xenon as treatments for acquired brain injury: a preclinical systematic review and meta-analysis

“… 29 , 30 The checklist was originally developed to assess preclinical models of ischaemic stroke, 29 , 30 but has been used for models of other neurological conditions including TBI, cardiac arrest, Alzheimer's disease, and Parkinson's disease. 63 , 64 , 65 , 66 , 67 There was one moderate-quality study in the argon group, that had the highest effect size of that group. There were seven moderate quality studies in the xenon group distributed equally on both sides of the summary effect estimate.…”

Therapeutic potential of mesenchymal stromal/stem cells in critical‐care patients with systemic inflammatory response syndrome

“… 33 , 34 , 35 The promising results obtained in these diseases have opened the MSCs’ clinical evaluation in new areas. 36 , 37 …”

Extracellular vesicle-loaded hydrogels for tissue repair and regeneration

“…Mesenchymal stem cells (MSCs) are pluripotent stem cells with multi-directional differentiation potential and self-renewal ability and have the potential to regenerate into various tissues, organs and cells [ 7 ]. MSC-related clinical research has been conducted extensively, and many significant breakthroughs have been achieved [ 8 , 9 ]. In addition to being used to restore hematopoietic function and treat autoimmune diseases, MSCs are also widely used to repair various types of tissue damage, such as in skin, bone and cartilage, heart and nerves [ 8 , [10] , [11] , [12] , [13] ].…”

“…MSC-related clinical research has been conducted extensively, and many significant breakthroughs have been achieved [ 8 , 9 ]. In addition to being used to restore hematopoietic function and treat autoimmune diseases, MSCs are also widely used to repair various types of tissue damage, such as in skin, bone and cartilage, heart and nerves [ 8 , [10] , [11] , [12] , [13] ]. However, as stem cell research has intensified, researchers have discovered that stem cell therapies are a double-edged sword: Although stem cells can promote tissue repair, their indefinable, multidirectional differentiation potential makes them potentially tumorigenic and poses a major ethical problem [ 14 , 15 ].…”