title: Involvement of Immune Responses in the Efficacy of Cord Blood Cell Therapy for Cerebral Palsy.
abstract: This study evaluated the efficacy of umbilical cord blood (UCB) cell for patients with cerebral palsy (CP) in a randomized, placebo-controlled, double-blind trial and also assessed factors and mechanisms related to the efficacy. Thirty-six children (ages 6 months to 20 years old) with CP were enrolled and treated with UCB or a placebo. Muscle strength and gross motor function were evaluated at baseline and 1, 3, and 6 months after treatment. Along with function measurements, each subject underwent (18)F-fluorodeoxyglucose positron emission tomography at baseline and 2 weeks after treatment. Cytokine and receptor levels were quantitated in serial blood samples. The UCB group showed greater improvements in muscle strength than the controls at 1 (0.94 vs. -0.35, respectively) and 3 months (2.71 vs. 0.65) after treatment (Ps<0.05). The UCB group also showed greater improvements in gross motor performance than the control group at 6 months (8.54 vs. 2.60) after treatment (P<0.01). Additionally, positron emission tomography scans revealed decreased periventricular inflammation in patients administered UCB, compared with those treated with a placebo. Correlating with enhanced gross motor function, elevations in plasma pentraxin 3 and interleukin-8 levels were observed for up to 12 days after treatment in the UCB group. Meanwhile, increases in blood cells expressing Toll-like receptor 4 were noted at 1 day after treatment in the UCB group, and they were correlated with increased muscle strength at 3 months post-treatment. In this trial, treatment with UCB alone improved motor outcomes and induced systemic immune reactions and anti-inflammatory changes in the brain. Generally, motor outcomes were positively correlated with the number of UCB cells administered: a higher number of cells resulted in better outcomes. Nevertheless, future trials are needed to confirm the long-term efficacy of UCB therapy, as the follow-up duration of the present trial was short.
authors.affiliation: 1 Department of Bionanotechnology, Gachon Medical Research Institute, Gachon University , Seongnam, Republic of Korea.
authors.forename: Mino
authors.initials: M
authors.lastname: Kang
authors.affiliation: 2 Department of Rehabilitation Medicine, CHA Bundang Medical Center, CHA University , Seongnam, Republic of Korea.
authors.forename: Kyunghoon
authors.initials: K
authors.lastname: Min
authors.affiliation: 2 Department of Rehabilitation Medicine, CHA Bundang Medical Center, CHA University , Seongnam, Republic of Korea.
authors.forename: Joonyoung
authors.initials: J
authors.lastname: Jang
authors.affiliation: 1 Department of Bionanotechnology, Gachon Medical Research Institute, Gachon University , Seongnam, Republic of Korea.
authors.forename: Seung Chan
authors.initials: SC
authors.lastname: Kim
authors.affiliation: 3 Department of Laboratory Medicine, CHA Bundang Medical Center, CHA University and CHA Medical Center Cord Blood Bank , Seongnam, Republic of Korea.
authors.forename: Myung Seo
authors.initials: MS
authors.lastname: Kang
authors.affiliation: 4 Department of Nuclear Medicine, CHA Bundang Medical Center, CHA University , Seongnam, Republic of Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Jang
authors.affiliation: 4 Department of Nuclear Medicine, CHA Bundang Medical Center, CHA University , Seongnam, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: 5 Department of Radiology, CHA Bundang Medical Center, CHA University , Seongnam, Republic of Korea.
authors.forename: Sang Heum
authors.initials: SH
authors.lastname: Kim
authors.affiliation: 6 Division of Hematology-Oncology, Department of Pediatrics, CHA Bundang Medical Center, CHA University , Seongnam, Republic of Korea.
authors.forename: Moon Kyu
authors.initials: MK
authors.lastname: Kim
authors.affiliation: 1 Department of Bionanotechnology, Gachon Medical Research Institute, Gachon University , Seongnam, Republic of Korea.
authors.forename: SeongSoo A
authors.initials: SA
authors.lastname: An
authors.affiliation: 2 Department of Rehabilitation Medicine, CHA Bundang Medical Center, CHA University , Seongnam, Republic of Korea.
authors.forename: MinYoung
authors.initials: M
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D002547:Cerebral Palsy / Q000097:blood / Q000503:physiopathology* / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007223:Infant; D008297:Male; D053580:Muscle Strength / Q000502:physiology; D049268:Positron-Emission Tomography / Q000379:methods; D018121:Receptors, Cytokine / Q000097:blood; D058570:TOR Serine-Threonine Kinases / Q000097:blood; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000097:blood; D051197:Toll-Like Receptor 4 / Q000097:blood; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D018121:Receptors, Cytokine; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D019788:Fluorodeoxyglucose F18; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases