Vol 7, No 2 (2012)

Development of the fundamental and clinical «regenerative medicine» is based on the progress of gene, stem cell and gene-cell biotechnologies. However, the reliable preclinical investigations on animal models and more over clinical trials stay far away from the available nowadays gene and cell constructions. Neuroscience is one of the fast growing fields of knowledge in biology and medicine. Pioneer experiments in neuroscience promises breakthrough in the innovative methods for treatment of neurodegenerative diseases in near future. This review addresses strategies for gene-cell therapy of neurodegenerative diseases by the example of amyotrophic lateral sclerosis. Precisely gene modification of mononuclear fraction of umbilical cord blood cells (UCBC) by dual cassette plasmid vectors is observed. Based on our own results of transplantation of genetically modified UCBC overexpressing recombinant neural cell adhesion molecule L1, vascular endothelial growth factor, fibroblast growth factor 2, and glial derived neurotrophic factor in different combinations we provide the experimental data for usefulness of transplantation of gene modified UCBC for treating neurodegenerative diseases. In the review we discuss the efficacy of gene modification of UCBC not only for secretion of recombinant proteins, but in increasing of transplanted cells survivability, their migration possibilities and capability to differentiate in endothelial, microglial and macroglial cell types.

At present, novel osteoinductive materials containing recombinant bone morphogenetic proteins (rhBMPs) are actively being developed for «regenerative medicine», traumatology and orthopedics. To evaluate the effect of rhBMPs in materials, the great interest is to study osteoinductive properties of the materials in experimental models in vivo. In this paper we show that application of bone morphogenetic protein rhBMP-2 in demineralized cancellous bone blocks provides great improving osteoinductivity of the material in the ectopic model subcutaneous implantation in rats. This improvement was reflected in multifold acceleration of mineralization and in active forming a new structured collagen matrix in the material. The model of ectopic subcutaneous implantation to rats is very convenience test system to detect increase in osteoinductivity of materials caused by application of rhBMP-2, and to identify features of ectopic bone formation in these materials.

In the model of adult rat spinal cord contusion on the Th9 level effect of the immediate transplantation of the human olfactory mucosa cell into the damaged area were studied. No immunosuppression was used. It was shown that transplanted cells were survived as long as 7 days after transplantation and located in rostral and caudal directions in white matter on the 2 mm distance from points of injections. It was shown also that transplanted cells migrated into peripheral zone of the damaged area. The size of damaged area in white and especially in gray matters were decreased after 30 and 60 days after transplantation. The same time after 30 days after transplantation the size of pathological cavities mostly in anterior column were obviously diminished and that number of undamaged myelinated nerve fibers were increased in number around the area of transplantation

Fetal cells enter into mother`s body during pregnancy and remain there for many years. In female body accumulate genetically foreign cells of all pregnancies, regardless of what they have ended (a miscarriage, an abortion or a childbirth). It is shown that fetal cells are found in various maternal tissues and organs including blood, bone marrow, liver, lungs and skin. The interaction nature of foreign cells entering the mothers body in a natural way with her own cells and immune system of mother can be extrapolated to the study of chimerism in the iatrogenic effects on the body, such as hematopoietic stem cell transplantation or blood transfusion. Natural fetomaternal microchimerism has important effect on the immune status of women contributing to development of autoimmune conditions and tolerance to transplants. Understanding the fact that fetal cells able to pass through the placental and blood brain barrier, to migrate in various tissues and to differentiate in multiple cell types can be used for development of cell therapy. The studies of long-term effects feto- maternal microchimerism can get more favorable and unfavorable prognostic criteria for womens health, but also able to fundamentally change the understanding of current principles of clinical genetics. This paper presents an overview of knowledge about microchimerism appeared during pregnancy and current views on the implications of this unique biological phenomenon.