Neural crest cells and their potential therapeutic applications

Neural crest (NC) is a population of cells, formed at the intersection between non-neural ectoderm and neural tube. Neural crest progenitors are multipotent, have capacity to extensive migration and self-renewal. They can be differentiated into various cells types from craniofacial skeletal tissues to components of peripheral nervous system. Influence of signaling molecules and transcription factors, which are expressed at the different stages regulate development of NC. The regulatory network of genes determines the processes of induction, specification, migration and differentiation of neural crest cells (NCC). The purpose of this article is to compare the characteristics of NCC, obtained from tissues of the embryo, fetus and adult; experimental strategies for obtaining NCC from embryonic stem cells, induced pluripotent stem cells, skin fibroblasts; comparison of the potential of different cell types for therapeutic use in a clinical setting. Embryonic stem NCC are differentiated to the trunk, cranial, cardiac, circumpharyngeal and vagal according to the area of their initial migration. Mature stem NCC can be obtained from the dorsal root ganglia, red bone marrow, hair follicle, skin, intestines, carotid body, heart, cornea, iris, dental pulp, hard palate and oral mucosa. Genetic mutations may lead to failure of regulation of NC development, which leads to many congenital human diseases such as cardiovascular defects, craniofacial abnormalities and intestinal aganglionosis, collectively known as neurocristopathies. The identification and isolation of multipotent stem NCC derived from adult tissues, embryonic stem cells, and induced pluripotent stem cells are promising source for regenerative medicine.

Morphofunctional features of proliferating cells exposed to PSMA peptide

The effect of the synthetic PSMA peptide on dividing cells of laboratory animals was studied. The experiment was carried out on male white laboratory mice of the BALB/c-line. The toxic effect of PSMA peptidi was evaluated at therapeutic (1.4 μg / kg of animal weight or 0.04 μg / animal) and subtoxic (140 μg / kg of animal weight or 4.0 μg / animal) doses. The cytotoxic effect of PSMA peptide on red bone marrow cells and cambial intestinal cells of the of laboratory mice was determined. A decrease in the proliferative activity of the colon crypt cells was revealed upon administration of a subtoxic dose of the PSMA peptide and there were no signs of toxic damage to the red bone marrow cells of animals. Key words: toxicity, proliferation, synthetic peptides, mitotic index, micronucleus test.

Estimation of radiation-induced health hazards from a “dirty bomb” attack with radiocesium under different assault and rescue conditions

In the case of a terrorist attack by a “dirty bomb”, blast injuries, external irradiation and the incorporation of radioactivity are to be expected. Departing from information about the radiological attack scenario with cesium-137 in the U.S. National Scenario Planning Guide, we estimated the radiological doses absorbed. Similar calculations were performed for a smaller plume size and a detonation in a subway. For conditions as described in the U.S. scenario, the committed effective dose amounted to a maximum of 848 mSv, even for very unfavorable conditions. Red bone marrow equivalent doses are insufficient to induce acute radiation sickness (ARS). In the case of a smaller plume size, the ARS threshold may be exceeded in some cases. In a subway bombing, doses are much higher and the occurrence of ARS should be expected. The health hazards from a dirty bomb attack will depend on the location and the explosive device. The derived Haddon matrix indicates that preparing for such an event includes education of all the medical staff about radiation effects, the time lines of radiation damages and the treatment priorities. Further determinants of the outcome include rapid evacuation even from difficult locations, the availability of a specific triage tool to rapidly identify victims at risk for ARS, the availability of an antidote stockpile and dedicated hospital beds to treat seriously irradiated victims.

Wide-Field Pixel Super-Resolution Colour Lensfree Microscope for Digital Pathology

Whole slide imaging enables scanning entire stained-glass slides with high resolution into digital images for the tissue morphology/molecular pathology assessment and analysis, which has increased in adoption for both clinical and research applications. As an alternative to conventional optical microscopy, lensfree holography imaging, which offers high resolution and a wide field of view (FOV) with digital focus, has been widely used in various types of biomedical imaging. However, accurate colour holographic imaging with pixel super-resolution reconstruction has remained a great challenge due to its coherent characteristic. In this work, we propose a wide-field pixel super-resolution colour lensfree microscopy by performing wavelength scanning pixel super-resolution and phase retrieval simultaneously on the three channels of red, green and blue (RGB), respectively. High-resolution RGB three-channel composite colour image is converted to the YUV space for separating the colour component and the brightness component, keeping the brightness component unchanged as well as enhancing the colour component through average filter, which not only eliminates the common rainbow artifacts of holographic colour reconstruction but also maintains the high-resolution details collected under different colour illuminations. We conducted experiments on the reconstruction of a USAF1951, stained lotus root and red bone marrow smear for performance evaluation of the spatial resolution and colour reconstruction with an imaging FOV >40 mm2.

Dosimetric Comparison of Exposure Pathways to Human Organs and Tissues in Radon Therapy

Three therapeutic applications are presently prescribed in the radon spas in Gastein, Austria: exposure to radon in a thermal bath, exposure to radon vapor in an exposure chamber (vapor bath), and exposure to radon in the thermal gallery, a former mine. The radiological exposure pathways to human organs and tissues in these therapeutic radon applications are inhalation of radon and radon progeny via the lungs, radon transfer from water or air through the skin, and radon-progeny deposition on the skin in water or air. The objectives of the present study were to calculate radon and radon-progeny doses for selected organs and tissues for the different exposure pathways and therapeutic applications. Doses incurred in red bone marrow, liver, kidneys, and Langerhans cells in the skin may be correlated with potential therapeutic benefits, while doses to the lungs and the basal cells of the skin indicate potential carcinogenic effects. The highest organ doses among the three therapeutic applications were produced in the thermal gallery by radon progeny via inhalation, with lung doses of 5.0 mSv, and attachment to the skin, with skin doses of 4.4 mSv, while the radon contribution was less significant. For comparison, the primary exposure pathways in the thermal bath are the radon uptake through the skin, with lung doses of 334 μSv, and the radon-progeny attachment to the skin, with skin doses of 216 μSv, while the inhalation route can safely be neglected.

Estimation of lymphocyte radiation doses after the ingestion of radionuclides of different tropicity

Assessment of the lymphocyte doses is relevant for solving a number of radiobiological problems, including the risk assessment of hemoblastosis (leukemia, multiple myeloma, lymphoma etc.), as well as the use of circulating lymphocytes as “natural biodosimeters”. The latter is because the frequency of chromosomal aberrations occurring in lymphocytes following radiation exposure is proportional to the accumulated dose. Assessment of doses to the circulating lymphocytes requires due account of: first, the dose accumulated by the lymphocyte progenitors in the red bone marrow; and second, the dose accumulated during lymphocyte circulation through lymphoid organs. The models presented by International Commission on Radiological Protection (ICRP-67, ICRP-100) allow calculating the dose for specific lymphoid organs based on known level of radionuclide intakes. A recently developed model of circulating T-lymphocyte irradiation takes into account all sources of exposure and age-related dynamics of T-lymphocytes: (1) exposure of lymphocyte progenitors in red bone marrow: (2) exposure of T-lymphocytes in the lymphoid organs, taking into account the proportion of resident lymphocytes and the residence time of circulating lymphocytes in the specific lymphoid organs. The objective of the study is to assess the dose coefficients allowing for the transition from the ingestion of 141,144Ce, 95Zr, 103,106Ru, 95Nb to the doses accumulated in circulating T-lymphocytes. For calculations, we used the dose coefficients from ICRP publications for specific lymphoid organs, as well as published data on the residence time of circulating lymphocytes in lymphoid organs and tissues. As a result, it was shown that the doses in circulating T-lymphocytes are higher than those in the red bone marrow, but lower than the doses to the colon wall. The dose coefficients were age dependent; the maximum values were typical for newborns. The obtained dose coefficients for 141,144Ce, 95Zr, 95Nb and 103,106Ru can be used to estimate the tissue and organ doses based on data on the frequency of chromosomal aberrations in peripheral blood lymphocytes.

Subacute Course of Chronic Radiation Syndrome Caused External Non-Uniform Radiation Exposure of Lost Source

Purpose: To analyze the features of the clinical course of chronic radiation syndrome (CRS) due to external non-uniform chronic exposure to prolonged household contact with a lost source of ionizing radiation. Material and methods: Analysis of 2 clinical observations of patients who developed subacutecourse of CRS and chronic radiation dermatitis due to external non-uniform exposure of the lost sources of ionizing radiation are presented. Results: Boy A. K. from the age of 1 year for 7 years was external radiation exposed (for 1.5 years non-uniform exposure ) to the total dose according EPR tooth enamel about 6.3 Gy, according to the data of retrospective dose recovery on red bone marrow using voxel modeling – 26 (19–37) Gy. F. V. V., male, 38 years, was external non-uniform radiation exposed for 5 months, the total dose according cytogenetic studies of 7.9 Gy (dose rate about 0.035 Gy/h). During the examination in the hospital, the patients were diagnosed with CRS. Within the framework of the bone marrow syndrome, deep thrombocytopenia, moderate leuko- and neutropenia, and moderate anemic syndrome were observed. The latter is not typical for the typical course of CRS and is a criterion indicating a subacute course of the disease. In addition, signs of chronic radiation dermatitis were found in the projection of the action of the ionizing radiation beam. After stopping the radiation exposure, the patients did not recover their hematopoietic function, and in the period of immediate consequences, they developed myelodysplastic syndrome (MDS) with further transformation into acute leukemia. Conclusion: 1. Accidental prolonged household or criminal contact with a source of ionizing radiation can lead to the formation of CRS with an atypical subacute course and the formation of MDS with transformation to acute leukemia in the outcome of the disease or in the period of its consequences. 2. It can be assumed that with external non-uniform radiation exposure, leading to the development of CRS and chronic radiation damage to the skin, agranulocytosis in the subacute course of CRS may be absent. 3. Adverse prognostic signs for the development of MDS and leukemia in the outcome or in the period of the consequences of subacute CRS with non-uniform exposure are long-lasting deep thrombocytopenia and anemic syndrome after the end of radiation exposure.

Peripheral blood hematopoietic stem cell pool in individuals chronically exposed to radiation over a long-term period

Changes in the peripheral blood cellular composition were observed in the long term period in the residents of the Techa riverside villages chronically exposed to radiation, which may be the consequence of structural and functional disorders in the pool of hematopoietic stem cells (HSC) and progenitor cells. Therefore, the study was aimed to quantify peripheral blood CD34+ cell pool in individuals chronically exposed to radiation over a long-term period. Sixty years after the onset of exposure, a total of 153 individuals were examined, who were divided into four groups: individuals exposed in utero and postnatally (the average postnatal absorbed dose was 570 mGy); individuals exposed only postnatally (the average postnatal absorbed dose was 790 mGy), and two comparison groups, in which the average postnatal absorbed dose to red bone marrow did not exceed 70 mGy. Absolute and relative peripheral blood CD34+ cell counts in chronically exposed individuals were assessed by flow cytometry. No changes in CD34+ cell counts compared to comparison group were revealed in the group of individuals exposed in utero and postnatally; no age-related changes were registered as well. However, a significant decline in absolute HSC and progenitor cell counts with increased absorbed dose to red bone marrow was observed. In the group of individuals exposed only postnatally, there was a significant increase in peripheral blood CD34+ cell counts compared to comparison group (p = 0.004 for absolute cell count; p = 0.009 for relative cell count), dose-dependent increase in peripheral blood HSC and precursor cell counts (p = 0.02 for absolute cell count; p = 0.03 for relative cell count), along with age-related decline in these cells’ counts (р = 0.02 for absolute cell count; p = 0.04 for relative cell count).

BCL-2, CDKN1A and ATM gene methylation in chronically exposed individuals

DNA methylation is the most common epigenetic modification, caused by ionizing radiation. There may be both hypermethylation, which suppresses transcription of gene promoter regions, and hypomethylation, resulting in gene activation. Both mechanisms may be involved in carcinogenesis. The study was aimed to assess methylation status of CpG islands in the protective system BCL-2, CDKN1A and ATM gene promoters in the peripheral blood cells of the chronically exposed individuals, living in the villages, located along the Techa River, over a long-term period. Methylation of BCL-2, CDKN1A and ATM gene promoter regions in 68 residents of the villages, located along the Techa River (Chelyabinsk region), was assessed by the real-time methylation-specific PCR. The group of exposed individuals included 54 people with accumulated dose to red bone marrow within the range of 0.09–3.51 Gy. The comparison group included 14 people, living in similar economic and social environment, with the dose to red bone marrow, accumulated during the whole life, not exceeding 70 mGy. The pilot study of exposed individuals over a long period of time after chronic low-dose radiation exposure revealed no significant changes in methylation levels of CpG islands in the CDKN1A, BCL-2, ATM gene promoter regions compared to the comparison group. None were revealed in the dose subgroups “87–994 mGy” and “over 1000 mGy”.