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The conference “Cell technologies in obstetrics, gynecology, neonatology and pediatric neurology”

November 7, 2013 Institute of Cell Therapy and Coordination Centre for Transplantation of Organs, Tissues and Cells of the Ministry of Health of Ukraine held a conference «Cell Technologies in Obstetrics, Gynecology, Neonatology and Pediatric Neurology», dedicated to the 10th anniversary of the Institute of Cell Therapy.

Many internationally scientists from the U.S., Europe, Singapore, and Korea together with leading national experts in the field of obstetrics, gynecology, oncology, pediatric neurology and neurosurgery were invited by the Institute of Cell Therapy. They also presented reports at the conference. Foreign colleagues presented Ukrainian audience the latest results of clinical studies on the effectiveness of stem cells in the treatment of hypoxic-ischemic brain damage of newborn and modern trends in the treatment of this disease with the use of advanced biotechnology possibilities.

Professor James Carroll, Georgia Regents University, USA, in his report, “Stem cells for neonatal hypoxic-ischemic injury” gave a theoretical justification and presented clinical experience in the use of cord blood stem cells in the treatment of neonatal hypoxic-ischemic brain injury. He also considered the pathophysiological aspects of this disease. The professor denoted that umbilical cord blood contains precursors of all cells, including neurons. But he emphasized the importance of high-quality cord blood collection by experienced staff to ensure the quality of the cell preparation. The report presents general data of preclinical studies and 7clinical cases, indicating the effectiveness of different types of stem cells for the treatment of brain injury. However, in experimental studies neuronal recovery with stem cells is not supported by the results of histological studies. Taking into account the innovativeness of this therapeutic approach, the speaker considered the need of more extensive clinical trials before definite declaring of its effectiveness. The professor also drew attention to the umbilical cord tissue as a valuable source of stem cells.

Dr. Jiun Lee, National University Health Systems, Singapore, in the report “Autologous umbilical cord blood cells for newborn infants with hypoxic-ischemic encephalopathy – a pilot study of therapeutic options and safety” also referred to these experimental studies, according to which the nucleated cells from umbilical cord blood reduce the manifestations of brain injury. The lecturer also emphasized that cord blood is a very available source of stem cells. This increases its value and options of clinical applications. The scientist presented the results of a pilot clinical study on the possibility of using the infusion of autologous cord blood cells for the treatment of brain injury in newborns. The study included newborns with the second and third stages of hypoxic-ischemic brain injury. Umbilical cord blood samples depleted from erythrocytes, with reduced plasma volume and processed at the Singapore Cord Blood Bank, using an automated method Sepax, were used for the treatment. The final product was administered four times: the first dose of cord blood stem cells patient received at the age of 12 hours and the second – after 24, 48 and 72 hours from the birth. Development of the child was monitored for 18 months, and during this period patients underwent MRI 2 times. According to the results of this clinical trial, the authors conclude about the therapeutic possibilities and safety of application of autologous cord blood for the treatment of hypoxic-ischemic brain injury. They indicate the need for multicenter randomized clinical trials of this therapeutic approach.

Dr. Dariusz Boruczkowski, Polish Stem Cell Bank (PBKM), presented a report on the experience of transplantation of hematopoietic and mesenchymal stem cells from umbilical cord blood of FamiCord group cryobanks that unites the leading stem cell banks in Europe, in particular PBKM. Dr. Boruchkovski noted that simultaneously with the umbilical cord blood, which is a recognized and widely used source of stem cells, in recent years, stem cells of the umbilical cord tissue, or so-called Whartons jelly, present new possibilities for the treatment of congenital and acquired diseases. Dariusz Boruchkovski introduced the first Polish cases of application of stem cells from Whartons jelly, the first European experience of using of neural progenitor cells derived from umbilical cord blood, and the results of 13 transplantations of allogeneic cord blood samples from FamiCord group cryobanks. Mesenchymal stem cells, treated in PBKM, were applied in 7 patients with acute and 3 ones with steroid-refractory chronic graft-versus-host disease. Recipients of allogeneic cord blood samples were 12 children: 3 with acute lymphoblastic leukemia, 1 with relapsed neuroblastoma after autologous hematopoietic stem cell transplantation, 2 with myelodysplastic syndrome, 1 with Fanconi anemia, 1 with Langerhans cell histiocytosis, 1 with chronic granulomatous disease, 1 with aplastic anemia, and 1 with acute myeloid leukemia. The autologous hematopoietic stem cell transplantation was performed in 16 month old baby with hypoxic-ischemic encephalopathy. 10 transplantations were performed in Poland and 3 in Hungary. All grafts survived, no complications or adverse reactions were observed, and only 1 patient had a transient fever. A child with neuroblastoma after 18 months had a relapse. Disease relapses occurred in 2 children with acute lymphoblastic leukemia. All other patients are in complete remission today. Functional improvement is observed in the boy with hypoxic-ischemic brain injury. Among patients with graft-versus-host disease 2 patients died from complications of the underlying disease, the other 8 were discharged in satisfactory condition. Thus, summarizing the results of 23 transplantations and literature data Dr. Boruchkovski concluded that cord blood stem cells and stem cells from Whartons jelly can be used in clinical practice.

Professor MinYung Kim from the Republic of Korea (CHA Bundang Medical Centre) in the report “Treatment of children with cerebral palsy with cord blood potentized by erythropoietin” emphasized that cerebral palsy is the main cause of disability in early childhood, and allogeneic cord blood has a therapeutic potential for treatment of this pathology. To study the efficacy and safety of allogeneic umbilical cord blood for the treatment of cerebral palsy a group of researchers led by Professor conducted a randomized placebo-controlled clinical trial, in which simultaneously with rehabilitation therapy patients were treated with cord blood stem cells, potentiated and not potentiated with erythropoietin. The study included 96 patients. Monitoring did not reveal any adverse effects of such therapy in a year. The authors concluded that combined treatment with infusions of allogeneic umbilical cord blood and rhEPO prevents degradation of motor and cognitive functions in children with cerebral palsy, which was accompanied by structural and metabolic changes in the brain.

Dr. Leonid Pichkur, the chief of the Department of Reconstructive Neurosurgery of the Romodanov Institute of Neurosurgery, presented an extremely interesting report on the resultsof neurotransplantation in 216 patients with cerebral palsy. Crisis of transplant rejection and other complications in the postoperative period were not observed. After 5-6 months after surgery in only 6% of children the patient’s condition remained unchanged, while in 78% treatment results were evaluated as good. In particular, there was noted a remarkable positive effect of neurotransplantation on motor recovery, improvement of basic locomotor acts, which was accompanied by a decrease in reflex activity of muscles in spastic cerebral palsy forms (in 186 patients). Thus, intrathecal transplantation of embryonic neural tissue obtained from fragments of 9-week -old embryo brain is an effective treatment of cerebral palsy. The best results are possible to achieve in children aged 3-6 years.

Professor Stanislav Yevtushenko from M. Gorky Donetsk National Medical University in his report “On the selection of the recipient with cerebral palsy for the effective application of cellular technology for medicinal purposes,” considered the effective application of stem cells in pediatric neurology. The author touched upon statistics, according to which 19,735 children with cerebral palsy are currently registered in Ukraine. Neurorehabilitation technique is mainly aimed at the adaptation of the patient to society, although the main task of medical rehabilitation is an improving of motor, speech and cognitive function in these patients. It is possible to approach the solution of the problems due to the achievements of modern biotechnology. The author recommends cell therapy for patients with cerebral palsy without signs of congenital anomalies of the brain and various heterotopias, according to MRI. The most perspective, in terms of the projected positive result, the reporter suggests children with low birth weight and only after less than 2 hours of hypoxia or the full-term children with hemiplegic cerebral palsy.

Deputy Director of the Cryobank of Institute of Cell Therapy Volodymyr Shabliy presented a report “Placental stem cells: biological characteristics and potential clinical applications”. The speaker noted that the placenta is an attractive source of mesenchymal stem cells and trophoblast stem cells for application in regenerative medicine. These cells are different origin, but have multipotent ability to differentiate into mesodermal, endodermal and ectodermal cell lines that showed a therapeutic potential in several preclinical studies. There were presented results of their own scientific researches on the cultivation of placental stem cells, conducted at the Institute of Cell Therapy.

A report on “Experimental approaches to the study of stem cells therapeutic potential in central nervous system perinatal pathology” presented PhD Oleg Tsupykov from Bogomoletz Institute of Physiology NAS Ukraine, focusing on the relevance of the search of non-drug correction methods of the damaged central nervous system functions. Numerous animal studies with different experimental models and modern instrumental methods confirm the high therapeutic potential of stem cells of different origin.

Peter Nemtinov presented an interesting report “Autologous transplantation of ovarian tissue to preserve fertility for women of reproductive age with cancer pathology”, which gave an overview of clinical births in women after transplantation of frozen ovarian tissue. 2004 Donnex J. and colleagues informed of the birth of the first child in the world after autologous transplantation of thawed cryopreserved ovarian tissue that was stored for a woman with cancer pathology, whose treatment was characterized by a high risk of infertility. Cryo-storage of ovarian tissue for cancer patients before gonadotoxic treatment is a common practice in developed countries. For example, in Denmark from 1996 to 2009 cryopreservation of ovarian tissue was conducted for 386 patients at the age from 6 months to 39.8 years. In Belgium ovarian tissue was cryopreserved for 582 patients for 15 years. In 2012 28 children were already born after autologous retransplantation of frozen ovarian tissue in the world. Currently, the service of cryopreservation of reproductive cells and tissues, including ovarian tissue, is available in Ukraine in Cryobank of Institute of Cell Therapy.

Dr. Volodymyr Klimov, Lugansk Medical University, presented report “The pathogenesis of endothelial dysfunction in fetoplacental complex in complicated pregnancy”. The reporter considered the role of activation of natural killer cells of endometrium in the development of the endothelial dysfunction in the “mother-placenta-fetus” system.

Dr. Vitaliy Kyryk, Head of Cell and tissue cultures laboratory of State Institute of Genetic and Regenerative Medicine NAMS of Ukraine in his report examined the role of endothelial progenitor cells in the development of preeclampsia, having concluded that the change in the number of circulating endothelial progenitor cells in blood of pregnant women may act as an additional marker in the early diagnosis and prevention of preeclampsia as well as testify to the risk of fetal abnormality.

Thus, data presented at the conference show that the development of new cell-based therapies and modern biotechnology opens up new possibilities for the treatment of a wide range of socially significant diseases and improve the quality of patients’ life.