Monocyte-derived macrophages for treatment of cerebral palsy: a study of 57 cases

Abstract

Objective: Cell-based technologies are considered to be a new approach for the treatment of cerebral palsy (CP). Given the potent anti-inflammatory activity and high regenerative potential of M2 macrophages, these cells may be a promising source for cell transplantation. To evaluate the safety and efficacy of autologous M2 macrophages, we performed an open-label, Phase I/ II, non-controlled clinical trial in children with severe CP. Patients and methods: Fifty-seven children with severe CP, including 33 boys and 24 girls, with a median age of 4 years were enrolled in the study. The patients were treated with intrathecal administration of autologous M2 macrophages. The primary outcome measure was safety, and the secondary outcome measure was functional improvement in neurologic scales, including the 66-item Gross Motor Function Measure test, Peabody Developmental Motor Scale-Fine Motor test, Ashworth scale, Medical Resarch Council scale, and an easy-to-understand unified questionnaire for evaluation of cognitive functions in our modification. Results: Intrathecal introduction of M2 cells in a median dose of 11.2×10 6 did not induce any serious adverse events either related with cell injection or during 5 years of follow-up. After 3 months, the Gross Motor Function Measure score increased from 19±4.5 to 77±7.8, the Peabody Developmental Motor Scale-Fine Motor test score improved from 0.9±0.23 to 4.4±0.51, and the Ashworth score decreased from 3.5±0.11 to 2.5±0.16. The assessment of cognitive functions revealed an increase from 1.22±0.24 to 3.98±0.95, and a reduction of seizure syndrome was registered. In addition, M2 injection was accompanied by an increased production of brainderived neurotrophic factor (p U =0.015). Conclusion: The data obtained suggest that cell therapy based on M2 macrophages is safe, does not induce any severe cell-related reactions or long-term side effects and comorbidities, and is accompanied by significant neurologic improvements in severe CP patients.

Role of the Monocyte–Macrophage System in Normal Pregnancy and Preeclampsia

“…Injection of the autologous monocyte-derived M2-polarized macrophages at a certain time of gestation (or at the stage of its planning by taking into account the risks of PE) may evolve into a new strategy for PE treatment. Such therapy seems to be promising due to reports about the absence of adverse reactions and long-term side effects after macrophages transplantation in other diseases [120,121]. A possible side effect of the proposed therapy may be the phenomenon of maternal–fetal cellular trafficking—the ability of mother and fetus cells pass the placental barrier [122].…”

Inhibition of NLRP3 inflammasome attenuates spinal cord injury‐induced lung injury in mice

“…Macrophage differentiate into two subsets with distinct expression profile, exerting different features and effects on their phenotypes (L. Chen, Sha et al, 2017;Chiu et al, 2016). M1 subset, is normally correlated with overwhelming inflammatory reaction, resulting in the release of proinflammatory cytokines, which potentially have detrimental effects on injured spinal cord (L. Chen, Sha et al, 2017); whereas the activation of M2 subset produces antiinflammatory mediators in injured spinal cord, exhibiting homeostasis, axonal regeneration, and neuroprotection (Chernykh et al, 2018;Chiu et al, 2016). Accordingly, the balance between M1 and M2 microglia subset is considered to play essential roles in pulmonary inflammation (Ying et al, 2015).…”

Traditional Chinese medicine-based neurorestorative therapy for Alzheimer’s and Parkinson’s disease

“…Moreover, G. biloba extract EGb 761 shifted proinflammatory to anti-inflammatory activation in the AD model of the P301S Tau mutant transgenic mice [54]. This suggested that EGb 761 may be used in the monocytes/macrophages cell-based technologies through the activation of anti-inflammatory cells in vitro because anti-inflammatory M2 macrophages successfully improved neurological functioning of patients with severe cerebral palsy (CP) [85]. The effects of TCM on immunomodulation and neuroinflammation observed in the in vivo study are similarto theeffects of different TCMs demonstrated in vitro, which are summarized in Table 4.…”