Oleg P. Tarakanov, Yury A. Romanov, Sergey M. Radaev, Tamara N. Dugina, Svetlana S. Ryaskina, Anna N. Darevskaya, Yana V. Morozova, Irina N. Proshkina, William A. Kchachatryan, Konstantin E. Lebedev, Nelly S. Zotova, Anna S. Burkova, Gennady T. Sukhikh and Vladimir N. Smirnov

National Cardiology Research Center, Moscow

Abstract:

In the course of clinical investigation the safety and efficacy of intravenous infusion of allogeneic HLA-mismatched umbilical cord blood (UCB) cells were studied in children with cerebral palsy and associated neurological complications. The “cell therapy” group was composed of 32 patients (1-11 years old, 23 male, 9 female) with confirmed clinical diagnosis “cerebral palsy” including 9 with spastic diplegia, 5 with hemi- and 12 with quadriplegia. In the majority of patients cerebral palsy was associated with other pathological conditions such as epilepsy (n=9), hydrocephalus (n=3), and optic nerve degeneration (n=6). Almost all children had a delay of physical and mental development. Control group included 16 patients with similar manifestations of disease undergoing conservative treatment. Cord blood was collected after informed consent during full-term normal deliveries from healthy women at the National Center of Obstetrics, Gynecology and Perinatology. Red blood cell-depleted/plasma-reduced nucleated cells were aseptically isolated by sedimentation, aliquoted in cryovials and cryopreserved. All samples were tested for HIV-1/2, hepatitis B and C, HTLV-1/2, HSV-1 and -2, CMV, syphilis (sero- and/or PCR-positive samples were discarded), characterized by AB0/Rh, CD34/CD45-positive cells content and sterility. Units approved for clinical application were subsequently transferred into liquid nitrogen and stored until use. For therapeutic application, UCB cells were thawed, washed from cryoprotectant, re-suspended in physiological saline containing 2.5 % human serum albumin/5% Dextran-40 and used within 1-2 hours. Signed by parents Informed consent forms were obtained for each patient before initiation of treatment and for each UCB cell infusion. Cells were introduced via peripheral vein using transfusion system with nylon filter (“dropper”); the time of procedure typically did not exceed 30 minutes. Vital signs were monitored during the infusion and for 2-3 hours after the procedure. According to treatment plan, patients received 2–4 intravenous infusions of AB0/Rh-identical UCB cells at the average dose of 250x106 viable cells per infusion with 2-3 week interval. Patients’ follow-up for 3-12 months demonstrated that multiple UCB cell infusions did not cause any adverse effects. On the contrary, in 80% of cases we observed positive dynamics related to statistically significant improvement of neurological status, motor functions and intellectual development. The decrease of pathological muscular tone, reduction of epileptic paroxysm frequency and amelioration in mental state were detected in 42, 33 and 57 percents of patients, respectively. Obtained results suggest that intravenous infusion of allogenic HLA-mismatched AB0/Rh-identical UCB cells may be considered as safe and effective procedure and could be included into programs of treatment and rehabilitation of juvenile patients with cerebral palsy. Furthermore, comparing to the use of autologous UCB cells, this approach allows  significantly expand the recruitment of infantile as well as adult patients suffering from various neurological conditions in which cell therapy approach could be applied.