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.

Mesenchymal stromal cells’ role in tumor microenvironment: involvement of signaling pathways

“…Failure or poor results following attempts of MSC-based therapy observed in a significant number of patients raised at least three concerns. First is their overall viability following infusion via the route used (local versus systemic 43 ); moreover, despite clinical evidence and reports from experimental models supporting the assumption that MSC homing may be governed by damaged tissues, MSCs can still be found in unwanted sites, thereby raising safety concerns for the long-term effects of MSC-based therapy 59,60 , particularly in pediatric patients 61-63 . Second is the engraftment degree of MSCs in targeted tissues, and the third, as a consequence, is the fate of these cells if improperly engrafted.…”

The First Decade of Advanced Cell Therapy Clinical Trials Using Perinatal Cells (2005–2015)

“…By comparison, in South Korea all advanced cell therapy for cerebral palsy has always been with allogeneic cord blood since the first registered trial in 2010 (NCT01193660). The ability to use allogeneic cells has enabled trials in South Korea to accrue patients much faster than the autologous trials in the USA, and the first publications that demonstrate the efficacy of perinatal cell therapy for cerebral palsy against control groups are from the South-Korea research pipeline [51][52][53]. This history illustrates that even the most thorough compilation of registered trials will still miss important emerging research that has not been registered, either because the trial is Phase I, or the host country does not require international trial registration, or the patients are treated under a compassionate exemption.…”

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

“…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.…”