Genetically modified human umbilical cord blood mononuclear cells as potential stimulators of neuroregeneration in degenerative disorders of central nervous system

Gene-cell therapy is a new step for the treatment of different human disorders including central nervous system degenerative diseases. In this review we focused on the last challenges in the field of human umbilical cord blood mononuclear cells transplantation - An attempt to support neuronal cells survival and to stimulate the neuroregeneration. As a potential therapy for the treatment of neurodegenerative diseases we reviewed the latest advances in gene modification of human umbilical cord blood mononuclear cells as a novel tool for the effective delivery of neuroprotective factors and growth factors in the injured or degenerative areas of the central nervous system under pathological conditions. The main topic of this review is the potential therapy of the amyotrophic lateral sclerosis - The progressive neurodegenerative disorder affecting primarily upper and lower motoneurons - by using genetically modified human umbilical cord blood mononuclear cells. The results from the up-to-date experiments indicated the opportunity to obtain differentiated macrophages, endothelial cells, or astrocytes from the genetically modified human umbilical cord blood mononuclear cells after their transplantation in the mouse model of the amyotrophic lateral sclerosis. Taken together, these data build the high-capacity platform for the supporting of degenerating neurons, structural and functional recovery of the brain and spinal cord after trauma, ischemia and other neurodegenerative disorders. © Human stem cells institute, 2013

Synaptosome-associated protein 25 (SNAP25) synthesis in terminal buttons of mouse motor neuron

© 2015, Pleiades Publishing, Ltd. Previously, we formulated the hypothesis of compartmentalized protein synthesis in axons of motor neurons. In the axon hillock, along the entire length of the axon and in its ending, specific proteins are locally synthesized, which ensure the function of each compartment. In support of this hypothesis, in this work we studied the local protein synthesis in mouse motor nerve ending

2,4-Diorganyl 1,3,2,4-dithiadiphosphetane-2,4-disulfides, their structure and S-silyl dithiophosphonic derivatives

© 2016 Taylor & Francis Group, LLC.Novel 2,4-diorganyl 1,3,2,4-dithiadiphosphetane-2,4-disulfideswere prepared by the reactions of tetraphosphorus decasulfide with butylphenyl ether or 3-brominephenyl-1-isoamyl ether in 1,2-dichlorobenzene. Their structures were established by X-ray single crystal diffraction. Chiral S-trimethylsilyl dithiophosphonates were prepared by the reactions of 2,4-diorganyl 1,3,2,4-dithiadiphosphetane-2,4-disulfides with trimethyl silyl ethers of monoterpenols. Unsaturated S-trimethylsilyl dithiophosphonates were synthesized by the reactions of 2,4-diorganyl 1,3,2,4-dithiadiphosphetane-2,4-disulfides with O-trimethylsilyl ethers of geraniol, nerol, and (R,S)-linalool. S-Esters of dithiophosphonic acids, which possessed antimicrobial activity, were prepared by the reactions of chiral S-trimethylsilyl dithiophosphonateswith orthoformiates, acetals and thioacetals

Synthesis of new lipophilic phosphine oxide derivatives of natural amino acids and their membrane transport properties toward carboxylic acids

© 2015 Pleiades Publishing, Ltd. One-pot procedures were developed for the synthesis of lipophilic N-(dialkylphosphorylmethyl) derivatives of natural amino acids with high yields from dioctyl- or didecylphosphine oxide, formaldehyde, and amino acid in the presence of amino acid hydrochloride. The reactions with some amino acids were also effective under catalysis by crown ether. The structure of the isolated N-(dialkylphosphorylmethyl) and N,N-bis(dialkylphosphorylmethyl)amino acids was determined on the basis of 1H, 13C, and 31P NMR and mass spectra; the structure of (S)-N-[(dicyclohexylphosphoryl)methyl]-α-alanine was proved by X-ray analysis, and intermolecular association of its molecules in crystal was characterized. Membrane transport properties of the new phosphorylated amino acids with respect to polyfunctional carboxylic acids were studied, and factors responsible for the efficiency and selectivity of membrane transport of acid substrates were estimated. Selective extraction of glutaric acid through a liquid membrane containing N,N-bis[(dioctylphosphoryl)methyl]-β-alanine was revealed

Treatment of the amyotrophic lateral sclerosis using of genetically modified umbilical cord blood mononuclear cells in the preclinical studies

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

Over-expression of Oct4 and Sox2 transcription factors enhances differentiation of human umbilical cord blood cells in vivo

Gene and cell-based therapies comprise innovative aspects of regenerative medicine. Even though stem cells represent a highly potential therapeutic strategy, their wide-spread exploitation is marred by ethical concerns, potential for malignant transformation and a plethora of other technical issues, largely restricting their use to experimental studies. Utilizing genetically modified human umbilical cord blood mono-nuclear cells (hUCB-MCs), this communication reports enhanced differentiation of transplants in a mouse model of amyotrophic lateral sclerosis (ALS). Over-expressing Oct4 and Sox2 induced production of neural marker PGP9.5, as well as transformation of hUCB-MCs into micro-glial and endothelial lines in ALS spinal cords. In addition to producing new nerve cells, providing degenerated areas with trophic factors and neo-vascularisation might prevent and even reverse progressive loss of moto-neurons and skeletal muscle paralysis. © 2014 Elsevier Inc. All rights reserved

Over-expression of Oct4 and Sox2 transcription factors enhances differentiation of human umbilical cord blood cells in vivo

© 2014 Elsevier Inc. All rights reserved. Gene and cell-based therapies comprise innovative aspects of regenerative medicine. Even though stem cells represent a highly potential therapeutic strategy, their wide-spread exploitation is marred by ethical concerns, potential for malignant transformation and a plethora of other technical issues, largely restricting their use to experimental studies. Utilizing genetically modified human umbilical cord blood mono-nuclear cells (hUCB-MCs), this communication reports enhanced differentiation of transplants in a mouse model of amyotrophic lateral sclerosis (ALS). Over-expressing Oct4 and Sox2 induced production of neural marker PGP9.5, as well as transformation of hUCB-MCs into micro-glial and endothelial lines in ALS spinal cords. In addition to producing new nerve cells, providing degenerated areas with trophic factors and neo-vascularisation might prevent and even reverse progressive loss of moto-neurons and skeletal muscle paralysis