Safety of Allogeneic Umbilical Cord Blood Stem Cells Therapy in Patients with Severe Cerebral Palsy: A Retrospective Study

Feng, Mei; Lü, Aiping; Gao, Hongxia; Qian, Caiwen; Zhang, Jun; Lin, Tongxiang; Zhao, Yuanqi

doi:10.1155/2015/325652

Cited by 52 publications

(48 citation statements)

References 25 publications

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“…34,35 Some follow-up safety data are becoming available. 36 Despite this recent progress, designing cell therapy studies remains challenging, and ethical concerns need to be addressed. Most of the data available to date originate from various parts of the world, and integrating the various regulatory and research methodology approaches remains a future challenge.…”

Section: New Therapeutic Resources and Researchmentioning

confidence: 99%

Report of a workshop on research gaps in the treatment of cerebral palsy

et al. 2016

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Cerebral palsy (CP) is heterogeneous in etiology and manifestations, making research into relevant therapies difficult and limiting the generalizability of the results. We report here on the NIH CP symposium, where stakeholders from academic, clinical, regulatory, and advocacy backgrounds discussed the major challenges and needs for moving forward with clinical research in CP, and outlined priorities and action items. New information is constantly generated through research into pathogenesis and etiology. Clinical research and new therapeutic approaches need to keep pace, through large data registry integration and new research designs. Development of standardized data collection, increasing academic focus on CP research, and iterative approaches to treatment throughout the patients' lives, have all been identified as areas of focus. The workshop identified critical gaps and areas of focus to increase the evidence base for therapeutic approaches to determine which treatments work best for which patients in the near future. These include consolidation and optimization of databases and registries, updates to the research methodology, and better integration of resources and stakeholders. DEFINING THE PROBLEM Cerebral palsy (CP) is a group of neurologic disorders of motor control with onset early in development and persistence throughout the lifespan. CP is the most common cause of motor disability in childhood, with an incidence of 2 to 3 per 1,000 live births, occurring 20 to 30 times more frequently in premature or low-birth-weight infants.1 These disturbances of movement and posture cause activity limitations.2 Those activity limitations resulting from spinal or neuromuscular disorders are excluded from the diagnosis. Various etiologies can cause the CP clinical spectrum but all have a disruption of motor control in common. In addition to prematurity, other known etiologies include developmental defects of the brain, perinatal stroke, hypoxia, shock, and fetal or neonatal inflammation/infection. However, CP may also occur in low-risk children for whom there is no obvious etiology or risk factor. CP is often accompanied by comorbidities such as seizures, communication deficits, hearing and vision deficits, and intellectual disability. There is a wide spectrum of functional outcomes from normal educational, career, and social activities to complete disability and dependence.An upper age limit for acquired pathology in the brain leading to CP is not absolute, but the onset of symptoms and the diagnosis are generally expected to occur by the age of 2. Given the heterogeneity in terms of etiology, pathology, clinical manifestations, and progression, it is best to consider CP as a collection of conditions rather than one uniform entity for developing treatment guidelines or conducting research on potential therapies.To address pressing research challenges, the National Institute of Neurological Disorders and Stroke (NINDS) organized a workshop with the main goal of discussing research needed to determine best ...

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Section: New Therapeutic Resources and Researchmentioning

confidence: 99%

Report of a workshop on research gaps in the treatment of cerebral palsy

et al. 2016

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“…There is currently no specific treatment for CP except for rehabilitation training in the clinic (Maclennan et al, ). Since the first transplantation of UCBCs was performed in 1988 (Mreboredo, Diaz, Castro, & Villaescusa, ), UCB‐SC therapy has been widely studied in children with CP, and improved brain cognition and gross motor function have been shown with no serious side effects indicating that the therapy is neuroprotective and safe (Feng et al, ; Huang et al, ; Kang et al, ; Lee et al, ; Min et al, ; Romanov et al, ; Sun et al, ) (Table ). However, current clinical trials focused on UCB‐SC therapy in children with CP have not considered the gestational age partition of the patients, and thus further research is needed regarding children with CP who were born prematurely.…”

Section: Ucb‐sc Therapy In Preterm Brain Injuries and Neurological Sementioning

confidence: 99%

Umbilical cord blood stem cell therapy in premature brain injury: Opportunities and challenges

Peng

Shi

et al. 2019

J of Neuroscience Research

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Preterm birth and associated brain injury are the primary cause of cerebral palsy and developmental disabilities and are among the most serious global health issues that modern society faces. Current therapy for infants suffering from premature brain injury is still mainly supportive, and there are no effective treatments. Thus there is a pressing need for comparative and translational studies on how to reduce brain injury and to increase regeneration and brain repair in preterm infants. There is strong supporting evidence for the use of umbilical cord blood (UCB)‐derived stem cell therapy for treating preterm brain injury and neurological sequelae. UCB‐derived stem cell therapy is effective in many animal models and has been shown to be feasible in clinical trials. Most of these therapies are still experimental, however. In this review, we focus on recent advances on the efficacy of UCB‐derived stem cell therapy in preterm infants with brain injury, and discuss the potential mechanisms behind their therapeutic effects as well as application strategies for future preclinical and clinical trials.

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“…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.…”

Section: Stem Cell Therapiesmentioning

confidence: 99%

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

et al. 2017

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Chorioamnionitis is a major cause of preterm birth and brain injury. Bacterial invasion of the chorion and amnion, and/or the placenta, can lead to a fetal inflammatory response, which in turn has significant adverse consequences for the developing fetal brain. Accordingly, there is a strong causal link between chorioamnionitis, preterm brain injury and the pathogenesis of severe postnatal neurological deficits and cerebral palsy. Currently there are no treatments to protect or repair against brain injury in preterm infants born after pregnancy compromised by intrauterine infection. This review describes the injurious cascade of events in the preterm brain in response to a severe fetal inflammatory event. We will highlight specific periods of increased vulnerability, and the potential effects of therapeutic intervention with cell-based therapies. Many clinical trials are underway to investigate the efficacy of stem cells to treat patients with cerebral palsy. Stem cells, obtained from umbilical cord tissue and cord blood, normally discarded after birth, are emerging as a safe and potentially effective therapy. It is not yet known, however, which stem cell type(s) are the most efficacious for administration to preterm infants to treat brain injury-mediated inflammation. Individual stem cell populations found in cord blood and tissue, such as mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs), have a number of potential benefits that may specifically target preterm inflammatory-induced brain injury. MSCs have strong immunomodulatory potential, protecting against global and local neuroinflammatory cascades triggered during infection to the fetus. EPCs have angiogenic and vascular reparative qualities that make them ideal for neurovascular repair. A combined therapy using both MSCs and EPCs to target inflammation and promote angiogenesis for re-establishment of vital vessel networks is a treatment concept that warrants further investigation.

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Safety of Allogeneic Umbilical Cord Blood Stem Cells Therapy in Patients with Severe Cerebral Palsy: A Retrospective Study

Cited by 52 publications

References 25 publications

Report of a workshop on research gaps in the treatment of cerebral palsy

Report of a workshop on research gaps in the treatment of cerebral palsy

Umbilical cord blood stem cell therapy in premature brain injury: Opportunities and challenges

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

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