Improvement in gross motor function and muscle tone in children with cerebral palsy related to neonatal icterus: an open-label, uncontrolled clinical trial

Abstract

Background Although stem cell transplantation has been successfully performed for cerebral palsy (CP) related to oxygen deprivation, clinical trials involving the use of stem cell transplantation for CP related to neonatal icterus have not been reported. The aim of this study was to evaluate the effectiveness of transplantation of autologous bone marrow mononuclear cell (BMMC) for improving gross motor function and muscle tone in children with CP related to neonatal icterus. Methods This open-label, uncontrolled clinical trial, which included 25 patients with CP related to neonatal icterus who had a Gross Motor Function Classification System (GMFCS) score between level II and level V, was conducted between July 2014 and July 2017 at Vinmec International Hospital (Vietnam). BMMC were harvested from the patients’ iliac crests. Two procedures involving BMMC transplantation via the intrathecal route were performed: the first transplantation was performed at baseline, and the second transplantation was performed 6 months after the first transplantation. Gross motor function and muscle tone were measured at three time points (baseline, 6 months, and 12 months) using the Gross Motor Function Measure (GMFM) and the Modified Ashworth Scale. Results In this trial, we observed significant improvement in gross motor function and a significant decrease in muscle tone values. Total score on the 88-item GMFM (GMFM-88), scores on each GMFM-88 domain, and the 66-item GMFM (GMFM-66) percentile were significantly enhanced at 6 months and 12 months after the first transplantation compared with the corresponding baseline measurements ( p -values < 0.05). In addition, a significant reduction was observed in muscle tone score after the transplantations ( p -value < 0.05). Conclusion Autologous BMMC transplantation can improve gross motor function and muscle tone in children with CP related to neonatal icterus. Trial registration ClinicalTrials.gov identifier: NCT03123562 . Retrospectively registered on December 26, 2017. Electronic supplementary material The online version of this article (10.1186/s12887-019-1669-2) contains supplementary material, which is available to authorized users.

The density of bone marrow mononuclear cells and CD34+ cells in patients with three neurologic conditions

“…Aging, injury, and acquired diseases can significantly change BMMNC components [ 28 ]. Some of our clinical trials using autologous BMMNCs for CP have shown the safety and initial effectiveness of the therapy [ 7 , 10 , 27 , 29 , 30 ].…”

“…In recent years, stem cell therapy for different neurologic conditions has become a new hope for patients. Bone marrow mononuclear cell therapy was one of the initial cell types used in clinical trials for the treatment of cerebral palsy [4,6,10,[24][25][26][27] and TBI [8,20]. Aging, injury, and acquired diseases can significantly change BMMNC components [28].…”

Oligodendrocyte Development and Implication in Perinatal White Matter Injury

“…However, a number of studies report pulmonary embolisms and accumulation of transplanted cells in undesired peripheral organs ( Steiner et al, 2012 ; Jung et al, 2013 ; Wu Z. et al, 2017 ). Other more direct routes of transplantation are intrathecal (IT) and intra-cerebral (IC) ( Zali et al, 2015 ; Nguyen et al, 2017 ; Thanh et al, 2019 ). The complexity of brain structure and variable localizations of WMI likely influence the selection of proper transplantation route ( Henriques et al, 2019 ).…”

Outcomes of Bone Marrow-Derived Mononuclear Cell Transplantation for Patients in Persistent Vegetative State After Drowning: Report of Five Cases

“…The number of BMMNCs that we collected each time is described in Table 1, and all the collected cells were used for transplantation. Based on our previous studies showing that BMMNC transplantation led to markedly improved gross motor function in patients with neurological complications such as cerebral palsy (12,35) and neurological sequelae due to intracranial hemorrhage (36), the ability of patient to sit up was selected as satisfactory criteria to evaluate if the patient needs additional transplantation. If the patient could not show the improvement as indicated by their ability to sit up after BMMNC transplantation, additional transplantation will be implemented but not more than four times.…”