Dose assessment for the Metlino and Muslyumovo populations who lived along the Techa river from 1949 to 1954

In the period from 1949 to 1956, liquid radioactive waste was routinely and accidentally discharged by the Mayak Production Association, Southern Urals, Russia, into the Techa river. Based on a novel approach, the contamination of the Techa river water, the bottom sediments and the adjacent flood plains was modelled, and internal and external doses were estimated for two villages located downstream of the site of liquid radioactive waste release. Altogether, 11 radionuclides that occurred in the liquid radioactive waste were included in the calculations. The results suggest significantly higher doses than previously assumed, with the major contribution in the year 1951. Radionuclides with half-lives of less than 1 year, such as ⁸⁹Sr, ¹³¹I, ⁹⁵Zr+⁹⁵Nb, ¹⁰³Ru+^103mRh, ¹⁴⁰Ba+¹⁴⁰La, and ¹⁴⁴Ce+¹⁴⁴Pr, represent the major sources and, in contrast, long-lived radionuclides, such as ⁹⁰Sr and ¹³⁷Cs that have so far been assumed to be most important, did not dominate the doses. For adults from the village Metlino, located 7 km downstream of the site of liquid radioactive waste discharge, the committed effective doses due to intake of radionuclides were calculated to be about 2.3 Sv, while the external doses were between about 1.2 Sv and 6.9 Sv. On the other hand, for adults from Muslyumovo, located 75 km downstream, the commited effective doses due to intake of radionuclides were calculated to be about 0.5 Sv, while the external doses were between 0.5 Sv and 2.0 Sv. The values for the skin doses to the Metlino and Muslyumovo populations were about 7.1 Sv and 1.3 Sv, respectively. It is concluded that the current dose estimates for the residents of the Techa river need, therefore, reevaluation.     

Method for comparative studies of the revascularisation processes in the bone tissue, using 85Sr

85SR was used for the local blood flow measurements in bones. A method for dynamic analysis of the magnitude of local blood flow based on 7-min analysis of the area under the logarithmic curve was presented. The radioactivity of the tibial diaphysis was followed by a gamma-scintillation dectector focused on the area of approximately 10 mm 0. The revascularisation process during bone repair after the osteotomy of the tibial diaphysis fixed intramarrowally was observed on 14 rabbits, two and four weeks after the osteotomy. In the first two weeks following the osteotomy the process of revascularisation was significantly enhanced in a comparison to the second two weeks.     

The relationship of bone marrow type and microvasculature to the microdistribution and local dosimetry of plutonium in the adult skeleton

Most plutonium-induced bone tumors in beagles arise in trabecular bone sites surrounded by hematopoietic tissue. The microvasculature and the relative incorporation of 241Pu (a low energy beta emitter) on trabecular bone surfaces from red and fatty marrow sites were studied in the adult beagle. The vascular volume, as determined by India ink perfusion, was about 16% in the red marrow and about 2% in the fatty marrow. The red marrow has large vascular sinusoids with a discontinuous endothelial lining whereas fatty marrow has a closed capillary bed. Plutonium concentrations on bone surfaces of red marrow sites are about 0.43 pCi/cm2/nCi/kg of injected dosage, a factor of eight greater than at fatty marrow sites (0.053 pCi/cm2/nCi/kg). The differences in the bone marrow microvasculature between red and fatty marrow help to explain differences in plutonium incorporation and local bone physiology in these skeletal sites. These observations may relate to the nonuniform distribution of plutonium-induced osteosarcomas observed in adult, long-lived mammals.     

In vivo studies on the regeneration kinetics of enriched populations of haemopoietic spleen colony-forming cells from normal bone marrow

Functional properties of mouse haemopoietic spleen colony-forming cells, enriched 40- to 80-fold, from normal bone marrow were studied. It was found that: (1) the number of partially purified CFU-s (colony forming unit-spleen) required to rescue lethally irradiated mice was similar to the number of normal unfractionated bone marrow CFU-s giving the same level of protection; (2) the homing of partially purified CFU-s was similar to that of CFU-s from unfractionated bone marrow; (3) the regeneration of CFU-s in spleen was similar for enriched and unfractionated cell populations between 4 and 11 days after transplantation. In contrast, the rate of regeneration of CFU-s in femur was slower with enriched progenitor cells than with unfractionated bone marrow. The growth rate in femur, however, could be restored to normal by injecting freshly isolated syngeneic thymocytes with the enriched CFU-s population. The results indicate that the partially purified CFU-s are by themselves functionally normal and show that the rate of CFU-s repopulation in bone marrow can be affected by cell types other than spleen colony-forming cells.     

Prospects for the future of bone marrow transplantation from the experimental studies on cells and animals

Despite accumulated extensive clinical experience bone marrow transplantation (BMT) remains a largely experimental procedure with high risk and numerous limitations. Part of the progress has to come from improvements in clinical care, but still as in former years there is a need of implementation of results of experiments on cells and animals. In the area of better engineering of posttransplant haemopoietic and immune cell production, this include variable pretransplant modifications of composition of inoculated cells as well as utilization of new drugs and growth factors. In the area of BM donor selection this includes identification of minor histocompatibility antigens. In the area of applications except for being a replacement therapy of haematologic disorders BMT may be considered as an adjunct therapy for transplantation of various organs. Finally, combination of cellular engineering of BM inoculum with genetic modifications of cells may offer therapy for some patients.     

Comparison of mesenchymal stem cells from adipose tissue and bone marrow for ischemic stroke therapy

Background aimsTransplantation of mesenchymal stromal cells (MSC) derived from bone marrow (BM) or adipose tissue is expected to become a cell therapy for stroke. The present study compared the therapeutic potential of adipose-derived stem cells (ASC) with that of BM-derived stem cells (BMSC) in a murine stroke model.MethodsASC and BMSC were isolated from age-matched C57BL/6J mice. These MSC were analyzed for growth kinetics and their capacity to secrete trophic factors and differentiate toward neural and vascular cell lineages in vitro. For in vivo study, ASC or BMSC were administrated intravenously into recipient mice (1 × 10⁵ cells/mouse) soon after reperfusion following a 90-min middle cerebral artery occlusion. Neurologic deficits, the degree of infarction, expression of factors in the brain, and the fate of the injected cells were observed.ResultsASC showed higher proliferative activity with greater production of vascular endothelial cell growth factor (VEGF) and hepatocyte growth factor (HGF) than BMSC. Furthermore, in vitro conditions allowed ASC to differentiate into neural, glial and vascular endothelial cells. ASC administration showed remarkable attenuation of ischemic damage, although the ASC were not yet fully incorporated into the infarct area. Nonetheless, the expression of HGF and angiopoietin-1 in ischemic brain tissue was significantly increased in ASC-treated mice compared with the BMSC group.ConclusionsCompared with BMSC, ASC have great advantages for cell preparation because of easier and safer access to adipose tissue. Taken together, our findings suggest that ASC would be a more preferable source for cell therapy for brain ischemia than BMSC.     

The content of 90Sr in the bone tissue of the population of the Soviet Union (1959 - 1971). (The basic laws of its accumulation and distribution).

On the basis of the results of long-term observations, general laws have been identified determining the dynamics of 90Sr concentration in the bone tissue of the population of the USSR in 1959-71, the peculiarities of 90Sr accumulation in different age groups and the connection and dependences between the intake and the contect of the isotope in human organism. It has been found that maximum 90Sr concentration occur in children born in the year when nuclear tests were carried out. The type of distribution of the frequency of occurrence of cases showing different levels of 90Sr content in uniform population groups was determined. Characteristic features of 90Sr distribution in different bones of the skeleton and its changes in the course of time were de monstrated.     

Comparison of mesenchymal stromal cells from human bone marrow and adipose tissue for the treatment of spinal cord injury

Background aimsBone marrow and subcutaneous adipose tissue are both considered prospective sources of mesenchymal stromal cells (MSCs), which can be used in cell therapy for spinal cord injury (SCI). The present study investigated whether human adipose tissue-derived mesenchymal stromal cells (hADSCs) transplanted into a rat model of SCI would lead to similar or improved neurologic effects compared with human bone marrow-derived mesenchymal stromal cells (hBMSCs).MethodshADSCs and hBMSCs were isolated from five adult donors. These MSCs were characterized using flow cytometry, immunocytochemistry, real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Immediately after SCI, 2 × 10⁵ hBMSCs or hADSCs were injected into the injured spinal cord. Locomotor function, cell survival and differentiation, spinal cord tissue morphology and brain-derived neurotrophic factor (BDNF) expression were compared between groups.ResultshADSCs and hBMSCs showed similar surface protein expression, and hADSCs showed higher proliferative activity with higher expression of vascular endothelial cell growth factor, hepatocyte growth factor and BDNF than hBMSCs. After transplant, both hADSCs and hBMSCs migrated within the injured spinal cord without differentiating into glial or neuronal elements. Administration of hADSCs was associated with marked changes in the SCI environment, with significant increases in BDNF levels. This was simultaneously associated with increased angiogenesis, preserved axons, decreased numbers of ED1-positive macrophages and reduced lesion cavity formation. These changes were accompanied by improved functional recovery.ConclusionsThe present results suggest that hADSCs would be more appropriate for transplant to treat SCI than hBMSCs.     

The protocol for the isolation and cryopreservation of osteoclast precursors from mouse bone marrow and spleen

Osteoclasts are responsible for physiological bone remodeling as well as pathological bone destruction in osteoporosis, periodontitis and rheumatoid arthritis, and thus represent a pharmacological target for drug development. We aimed to characterize and compare the cytokine-induced osteoclastogenesis of bone marrow and spleen precursors. Established protocols used to generate osteoclasts from bone marrow were modified to examine osteoclastogenesis of the spleen cells of healthy mice. Osteoclast formation was successfully induced from spleen precursors using receptor activator of nuclear factor κB ligand (50 ng/ml) and macrophage colony stimulating factor (50 ng/ml). Compared to bone marrow cultures, differentiation from spleen required a longer cultivation time (9 days for spleen, as compared to 5 days for marrow cultures) and a higher plating density of non-adherent cells (75,000/cm² for spleen, as compared to 50,000/cm² for bone marrow). Osteoclasts generated from spleen precursors expressed osteoclast marker genes calcitonin receptor, cathepsin K and matrix metalloproteinase 9 and were capable of resorbing hydroxyapatite. The differentiation capacity of spleen and bone marrow precursors was comparable for BALB/c, C57BL/6 and FVB mice. We also developed and tested a cryopreservation protocol for the osteoclast precursors. While 70–80 % of cells were lost during the first week of freezing, during the subsequent 5 weeks the losses were within 2–5 % per week. Osteoclastogenesis from the recovered bone marrow precursors was successful up to 5 weeks after freezing. Spleen precursors retained their osteoclastogenic capacity for 1 week after freezing, but not thereafter. The described protocol is useful for the studies of genetically modified animals as well as for screening new osteoclast-targeting therapeutics.     

The efficiency of in vitro isolation and myogenic differentiation of MSCs derived from adipose connective tissue,bone marrow,and skeletal muscle tissue

The objective of the study is to evaluate efficiency of in vitro isolation and myogenic differentiation of mesenchymal stem cells (MSCs) derived from adipose connective tissue (AD-MSCs), bone marrow (BM-MSCs), and skeletal muscle tissue (MC-MSCs). MSCs were isolated from adipose connective tissue, bone marrow, and skeletal muscle tissue of two adult 6-wk-old rats. Cultured MSCs were treated with 5-azacytidine (AZA) to induce myogenic differentiation. Isolated MSCs and differentiated cells were evaluated by immunocytochemistry (ICC), fluorescence-activated cell sorting (FACS), PCR, and RT-PCR. AD-MSCs showed the highest proliferation rate while BM-MSCs had the lowest one. In ICC, isolated MSCs had strong CD90- and CD44-positive expression and negative expression of CD45, CD31, and CD34, while AZA-treated MSCs had strong positive desmin expression. In FACS analysis, AD-MSCs had the highest percentage of CD90- and CD44-positive-expressing cells (99% and 96%) followed by BM-MSCs (97% and 94%) and MC-MSCs (92% and 91%).At 1 wk after incubation with AZA treatment, the peak of myogenin expression reached 93% in differentiated MC-MSCs, 83.3% in BM-MSCs, and 77% in AD-MSCs. MSCs isolated from adipose connective tissue, bone marrow, and skeletal muscle tissue have the same morphology and phenotype, but AD-MSCs were the most easily accessible and had the highest rate of growth on cultivation and the highest percentage of stem cell marker expression. Moreover, although MC-MSCs showed the highest rate of myogenic differentiation potential and expression of myoblast markers, AD-MSCs and BM-MSCs still can be valuable alternatives. The differentiated myoblastic cells could be an available new choice for myoblastic auto-transplantation in regeneration medicine.