III all-Russian Conference on pediatric neurosurgery
Clinical testing of M2-like macrophages in the treatment of cerebral palsy.
Kafanova M. Y., Adonina E. I., Shevela E. Ya., Sakhno L. V., Tikhonova M. A., Ostanin A. A., Chernykh E. R
MBUZ "Children's city clinical hospital №1", Institute of clinical immunology RAMS, Novosibirsk, Russia.
It is known that macrophages play a key role in tissue repair, but their role in CNS pathology remains controversial. On the one hand, macrophage-produced proinflammatory mediators can have a toxic effect on neurons and glial cells. On the other hand, recent studies have shown that macrophages can have a neuroprotective effect and stimulate the growth and myelination of axons.
The positive effect of macrophages is associated with clearance of cellular detritus and inhibitory molecules, restriction of glutamate-mediated cytotoxicity, production of growth and neurotrophic factors, as well as recruitment of neural precursors and T-cells. Opposite effects of macrophages are associated with their functional heterogeneity. Thus, classical Pro-inflammatory macrophages (M1) cause tissue destruction, while anti-inflammatory (M2) macrophages are involved in tissue repair. Using growth-deficient cultivation conditions, we have developed a method for generating M2 macrophages with low proinflammatory activity and significant regenerative potential ( in particular, producing high levels of IGF-1 and VEGF).
The aim of this work was to assess the safety and efficacy of these cells in the treatment of children with cerebral palsy (cerebral palsy). The study selected sixteen children (2 to 8 years) with IV and V levels of motor disorders. Endolumbal administration of M2-like cells was accompanied by fever in 10 (62.5%) people. No local / systemic allergic reactions, hematomas, or infected complications were observed. After 3 months after treatment, the Eshworth mean score ( spasticity) decreased from 3.9± 0.2 to 3.1± 0.2 ( Pu<0.01), the motor function score ( GMFM) improved from 12.1± 9.0 to 60± 19 (Pu<0.01).
Positive dynamics was manifested in the ability to hold the head ( 83% of children) , sit ( 53% of cases), crawl ( 43%) and even in some cases ( 12.5%) walk. Three out of six children with convulsive syndrome had cessation of seizures, and four had improved mental functions. Positive effects did not regress during the whole follow-up period ( more than a year in some children).
The introduction of M2-macrophages was not accompanied by an increase in IFN-gamma and IL-17 in serum, but led to an increase in BDNF and VEGF.These data indicate that the use of M2-macrophages is safe and according to preliminary data improves the neurological status in children with cerebral palsy. However, further clinical studies in the design of randomized prospective trials with long-term effects analysis are required to finally evaluate the effects of these cells.