Stem cell-based therapy is 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 an alternative source for cell transplantation. To evaluate the safety and efficacy of autologous M2 macrophages, we conducted a pilot clinical trial in 21 children with severe CP. The primary outcome measure was safety, which included assessment of mortality of any cause, immediate adverse reactions, and serious adverse effects and comorbidities during 5-year follow-up. The secondary outcome measure was functional improvement in Gross Motor Function Measure (66-item GMFM) test, Peabody Developmental Motor Scale-Fine Motor (PDMS-FM) test, Ashworth scale, MRC scale, and an easy-to-understand questionnaire for evaluation of cognitive functions in our modification. Intradural injection of M2 cells (in mean dose of 0.8 × 10(6)/kg) into the lumbar spinal area did not induce any serious adverse events. No cases of mortality, psychomotor worsening, exacerbation of seizures, and long-term comorbidities, including tumors, were observed during a 5-year follow-up. After 3 months, GMFM score increased from 13.7 ± 7.8 to 58.6 ± 14.6, PDMS-FM score improved from 0.76 ± 0.42 to 5.05 ± 0.97, and the Ashworth score decreased from 3.8 ± 0.21 to 3.3 ± 0.24. Along with gross and fine motor function enhancement, an improvement of cognitive activity (from 1.62 ± 0.41 to 4.05 ± 0.64, according to questionnaire assessment) and reduction of seizure syndrome were registered as well. The neurological improvements did not diminish during the 5-year follow-up period. The data obtained suggest that cell therapy based on M2 macrophages is safe, does not induce early adverse effects and long-term comorbidities, and is accompanied with a significant improvement of motor and cognitive activities in severe CP patients. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.
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.
The paper presents the results of a controlled study of cell therapy in 30 patients with severe forms of cerebral palsy. A cell suspension from immature nervous and hemopoietic tissues was injected into the subarachnoidal space of a recipient through a spinal puncture. Immune sensitization to donor antigens (detected by suppression of lymphocyte migration) was noted in few patients. In none patients laboratory and clinical signs of tissue-destructive autoimmune reactions were observed. One year after treatment activity of the major psychomotor functions in treated patients considerably surpassed the normal. No delayed complications of cell therapy were noted. These findings suggest that cell therapy is an effective, safe, and immunologically justified method of therapy for patients with cerebral palsy.
Cell suspension consisting of cells from immature nervous and hemopoietic tissues was transplanted subarachnoidally to patients with craniocerebral injury aftereffects. In some patients cell therapy led to immune sensitization to donor antigens, detected by the leukocyte migration inhibition test. No signs of tissue-destructive autoimmune reactions were detected in patients receiving cell therapy. Follow-up of 56 patients showed that cell therapy was associated with significant improvement of the neurological status. No serious complications of this treatment modality were observed. Presumably, cell therapy is a safe method which can be used in the treatment of craniocerebral injury aftereffects.
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