Concise Review: Stem Cell Interventions for People With Cerebral Palsy: Systematic Review With Meta-Analysis

Abstract

Evidence for stem cells as a potential intervention for cerebral palsy is emerging. Our objective was to determine the efficacy and safety of stem cells for improving motor and cognitive function of people with cerebral palsy. Searches were conducted in October 2015 in CENTRAL, EMBASE, MEDLINE, and Cochrane Libraries. Randomized controlled trials and controlled clinical trials of stem cells for cerebral palsy were included. Two authors independently decided upon included trials, extracted data, quality, and risk of bias. The primary outcome was gross motor function. Secondary outcomes were cognitive function and adverse events (AEs). Effects were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI), using a random-effects model. Five trials comprising 328 participants met inclusion criteria. Four cell types were studied: olfactory ensheathing, neural, neural progenitors, and allogeneic umbilical cord blood (UCBs). Transplantation procedures differed from central nervous system neurosurgical transplantation to intravenous/arterial infusion. Participants were followed short-term for only 6 months. Evidence of variable quality indicated a small statistically significant intervention effect from stem cells on gross motor skills (SMD 1.27; 95% CI 0.22, 2.33), with UCBs most effective. There were insufficient and heterogeneous data to compare cognitive effects. Serious AEs were rare (n = 4/135 [3%] stem cells; n = 3/139 [2%] controls). Stem cells appeared to induce short-term improvements in motor skills. Different types of stem cell interventions were compared, meaning the data were heterogeneous and are a study limitation. Further randomized controlled trials are warranted, using rigorous methodologies. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1014-1025 SIGNIFICANCE Stem cells are emerging as a scientifically plausible treatment and possible cure for cerebral palsy, but are not yet proven. The lack of valid animal models has significantly hampered the scope of clinical trials. Despite the state of current treatment evidence, parents remain optimistic about the potential improvements from stem cell intervention and feel compelled to exhaust all therapeutic options, including stem cell tourism. Receiving unproven therapies from unvalidated sources is potentially dangerous. Thus it is essential that researchers and clinicians stay up to date. A systematic review and meta-analysis summarizing and aggregating current research data may provide more conclusive evidence to inform treatment decision making and help direct future research.

Treatment and re/habilitation of children with cerebral palsy in India: a scoping review

“…Among medical interventions, autologous stem‐cell therapy was a prominent intervention used by Indian physicians, supposedly to improve a child's function. Evidence suggests that stem‐cell therapy is generally well tolerated and may provide short‐term improvements in motor skills (although the quality of the evidence is not strong); clearly, large and rigorous trials are needed to establish effectiveness . Weak‐to‐non‐existent regulations and policies to safeguard patients against exploitation and harmful exposure to unproven treatments (including stem‐cell ‘therapy’) contribute to encourage a flourishing stem‐cell tourism in India .…”

Human Umbilical Cord Blood Therapy Protects Cerebral White Matter from Systemic LPS Exposure in Preterm Fetal Sheep

“…UCB cells are safe and feasible as a therapeutic option in children with CP, and a recent meta-analysis investigating the efficacy of UCB across randomised controlled trials has demonstrated that UCB, alongside rehabilitation, is more effective at improving motor deficits than rehabilitation alone [14]. However, this preclinical animal study is the first to show that human UCB cells are protective for white matter development specifically in response to an inflammatory insult.…”

“…There is growing interest in the use of human umbilical cord blood (UCB) cells as a neuroprotective/neuroregenerative therapy for neurological disorders, in both paediatric and adult medicine [14]. Indeed, there are a number of clinical trials for the examination of UCB in infants and children with CP [15], and results to date support that UCB transplantation in children with established CP is associated with improved motor function with a low risk of adverse events [16].…”

Perinatal Brain Injury As a Consequence of Preterm Birth and Intrauterine Inflammation: Designing Targeted Stem Cell Therapies

“…Clinical trials have demonstrated the safety of UCB administration to children with established CP (Lee et al, 2012; Feng et al, 2015; Novak et al, 2016). Currently, however, it remains unclear how effective UCB could be in the setting of chorioamnionitis and preterm birth.…”

“…Novak and colleagues recently reviewed the evidence for the use of stem cells in improving gross motor function in children with CP (Novak et al, 2016); four randomized clinical trials and one non-randomized clinical trial were included for analysis. Two of these trials involved the use of allogeneic UCB transplantation (Min et al, 2013; Kang et al, 2015).…”