| Autor: |
Nguyen T; Department of Paediatrics, Monash University, Melbourne, VIC 3168, Australia., Purcell E; Department of Paediatrics, Monash University, Melbourne, VIC 3168, Australia., Smith MJ; The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia.; Department of Obstetrics and Gynaecology, Monash University, Melbourne, VIC 3168, Australia., Penny TR; The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia.; Department of Obstetrics and Gynaecology, Monash University, Melbourne, VIC 3168, Australia., Paton MCB; Cerebral Palsy Alliance Research Institute & Specialty of Child and Adolescent Health, The University of Sydney, Sydney, NSW 2006, Australia., Zhou L; Department of Paediatrics, Monash University, Melbourne, VIC 3168, Australia.; The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia.; Monash Newborn, Monash Children's Hospital, Melbourne, VIC 3168, Australia., Jenkin G; The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia.; Department of Obstetrics and Gynaecology, Monash University, Melbourne, VIC 3168, Australia., Miller SL; The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia.; Department of Obstetrics and Gynaecology, Monash University, Melbourne, VIC 3168, Australia., McDonald CA; The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia.; Department of Obstetrics and Gynaecology, Monash University, Melbourne, VIC 3168, Australia., Malhotra A; Department of Paediatrics, Monash University, Melbourne, VIC 3168, Australia.; The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC 3168, Australia.; Monash Newborn, Monash Children's Hospital, Melbourne, VIC 3168, Australia. |
| Abstrakt: |
Perinatal brain injury is a major contributor to long-term adverse neurodevelopment. There is mounting preclinical evidence for use of umbilical cord blood (UCB)-derived cell therapy as potential treatment. To systematically review and analyse effects of UCB-derived cell therapy on brain outcomes in preclinical models of perinatal brain injury. MEDLINE and Embase databases were searched for relevant studies. Brain injury outcomes were extracted for meta-analysis to calculate standard mean difference (SMD) with 95% confidence interval (CI), using an inverse variance, random effects model. Outcomes were separated based on grey matter (GM) and white matter (WM) regions where applicable. Risk of bias was assessed using SYRCLE, and GRADE was used to summarise certainty of evidence. Fifty-five eligible studies were included (7 large, 48 small animal models). UCB-derived cell therapy significantly improved outcomes across multiple domains, including decreased infarct size (SMD 0.53; 95% CI (0.32, 0.74), p < 0.00001), apoptosis (WM, SMD 1.59; 95%CI (0.86, 2.32), p < 0.0001), astrogliosis (GM, SMD 0.56; 95% CI (0.12, 1.01), p = 0.01), microglial activation (WM, SMD 1.03; 95% CI (0.40, 1.66), p = 0.001), neuroinflammation (TNF-α, SMD 0.84; 95%CI (0.44, 1.25), p < 0.0001); as well as improved neuron number (SMD 0.86; 95% CI (0.39, 1.33), p = 0.0003), oligodendrocyte number (GM, SMD 3.35; 95 %CI (1.00, 5.69), p = 0.005) and motor function (cylinder test, SMD 0.49; 95 %CI (0.23, 0.76), p = 0.0003). Risk of bias was determined as serious, and overall certainty of evidence was low. UCB-derived cell therapy is an efficacious treatment in pre-clinical models of perinatal brain injury, however findings are limited by low certainty of evidence. |
