4.6 Review

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

Journal

NPJ REGENERATIVE MEDICINE
Volume 6, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41536-021-00182-8

Keywords

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Funding

  1. Ministero Della Salute (Italy) [GR-2016-02361904]
  2. PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) FEDER, through the Competitiveness Internationalization Operational Programme (POCI)
  3. Foundation for Science and Technology (FCT) by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) [PTDC/DTP-FTO/5109/2014, POCI-01-0145-FEDER-029206, POCI-01-0145-FEDER-031392, PTDC/MED-NEU/31417/2017, NORTE-01-0145-FEDER-029968, UIDB/50026/2020, UIDP/50026/2020, NORTE-01-0145-FEDER-000013, NORTE-01-0145-FEDER-000023]
  4. European Molecular Biology Organization (EMBO)
  5. Fundação para a Ciência e a Tecnologia [PTDC/DTP-FTO/5109/2014] Funding Source: FCT

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Mesenchymal stromal cell (MSC) therapy in preclinical models of traumatic brain injury shows promising results with large effect sizes in improving sensorimotor, cognitive, and anatomical outcomes. Studies suggest that delivering MSCs in the first week post-injury, implanting them directly into the lesion cavity, or embedding them in matrices leads to greater efficacy in improving TBI outcomes.
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.

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