Outcomes of Bone Marrow Mononuclear Cell Transplantation for Neurological Sequelae Due to Intracranial Hemorrhage Incidence in the Neonatal Period: Report of Four Cases

Abstract

The aim of this study was to present primary outcomes of autologous bone marrow mononuclear cell (BMMNC) transplantation to improve neurological sequelae in four children with intracranial hemorrhage (ICH) incidence during the neonatal period. Methods: GMFM88 and modified Ashworth score were used to assess motor function and muscle spasticity before BMMNC transplantation and after transplantation. Brain MRI was performed to evaluate brain morphology before and after BMMNC transplantation. Bone marrow were harvested from anterior iliac crest puncture and BMMNCs were isolated using Ficoll gradient centrifugation. The microbiological testing, cell counting, and hematopoietic stem cell (hHSC CD34+ cell) analysis were performed, following which BMMNCs were infused intrathecally. Results: Improvement in motor function was observed in all patients after transplantation. In addition, muscle spasticity was reduced in all four patients. Conclusion: Autologous BMMNC transplantation may improve motor function and reduce muscle spasticity in children with ICH incidence during the neonatal period.

Mesenchymal Stem Cells Transplantation in Intracerebral Hemorrhage: Application and Challenges

“…Meanwhile, Safety evaluation results showed both doses of MSCs did not induce the serious adverse events and dose-limiting toxicity, and the mortality was zero even in grade 4 IVH, which implied this strategy was safe when the dose was controlled within 1 × 10 7 cells/kg of MSCs. As severe IVH and subsequent posthemorrhagic hydrocephalus could cause long-term neurological disorders in surviving preterm infants, children with neurological sequelae underwent a noteworthy clinical trial in which they were treated with bone marrow-derived mononuclear cells (BMMNCs) that might have the synergic effect of hematopoietic stem cells (HSCs) and MSCs ( Liem et al, 2019 ). Except for no observed any adverse side effect, BMMNC transplantation had made great progress in many aspects of neurodevelopment, such as motor function, fine motor skill, personal social, motor adaptive, and language skills, demonstrating the BMMNCs treatment effectiveness in promoting the social interaction and self-care ability of these children.…”

“…Nevertheless, this trend of cell source balance had been tilted in human research. Except for a small amount of MSCs derived from umbilical cord or cord blood ( Chang et al, 2016 ; Ahn et al, 2018 ), most of the transplanted MSCs were extracted through autologous bone marrow puncture in the clinical studies ( Liem et al, 2019 ; Zahra et al, 2020 ). Different from this, the bone marrow-MSCs in the rodent studies were mainly derived from allogeneic femur and tibia.…”

“…Although the improved prognosis of MSC treatment had been widely reported, the results of animal studies were mainly histopathological examination and neurological evaluation ( Liu et al, 2019 ), and the clinical studies were more about blood composition testing and neurological function scores ( Zhang, 2016 ; Brunet et al, 2019 ). In fact, clinical results about MSCs treated ICH were more of a case report for the patients ( Liem et al, 2019 ). The lack of control studies not only made the results occasional, but also greatly compromised the quality of clinical trials.…”

The Role of Stem Cells in the Therapy of Stroke

“…According to numerous studies, SC therapy supports neuroregeneration and neuroprotection not only in ischemic stroke but in intracerebral hemorrhage (ICH) [ 62 , 90 , 121 , 122 ], including subarachnoid hemorrhage [ 123 , 124 ].…”

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.…”