Enrichment and preserved functionality of multipotential stromal cells in bone marrow concentrate processed by vertical centrifugation

The concentration of bone marrow (BM) aspirate (BMA) is increasingly valued for bone and cartilage repair, particularly with the rarity and donor-variability of BM-multipotential stromal cells (BM-MSCs). The present study aimed to assess BM-MSC yield following BM concentration using a fast and compact-sized vertical centrifugation system. BMA concentrate (BMAC) was separated in a 1 min process and collected easily after an automatic discarding of plasma and red blood cells. A significant increase in CD45low CD271high cells per BMAC volume (measured using flow-cytometry) was noted (4-fold, p = 0.0001). Additionally, the vertical centrifugation system helped to enrich colony numbers (assessed by CFU-F assays) in BMAC comparably with conventional centrifugation systems, BioCUE™ and SmartPReP-2® (4.3-fold, 4.6-fold and 3-fold, respectively). Next, a functional assessment of BM-MSCs processed by vertical centrifugation was performed, and MSC viability and proliferation were not affected. Also, these BM-MSCs showed similar alkaline phosphatase and calcium levels to those of BMA-MSCs when osteogenically induced. Furthermore, glycosaminoglycans and Nile red levels in addition to the gene expression assays confirmed that there was no significant change in chondrogenic or adipogenic abilities between BMA-MSCs and BMAC-MSCs. The expression levels of selected angiogenic and immunomodulatory mediators were also similar between the two groups. Collectively, the vertical centrifugation system helped to enrich BM-MSCs effectively, while maintaining cell viability and functions. Thus, such a vertical centrifugation system for BM concentration can be valuable for various regenerative therapies

AHTR Mechanical, Structural, and Neutronic Preconceptual Design

This report provides an overview of the mechanical, structural, and neutronic aspects of the Advanced High Temperature Reactor (AHTR) design concept. The AHTR is a design concept for a large output Fluoride salt cooled High-temperature Reactor (FHR) that is being developed to enable evaluation of the technology hurdles remaining to be overcome prior to FHRs becoming a commercial reactor class. This report documents the incremental AHTR design maturation performed over the past year and is focused on advancing the design concept to a level of a functional, self-consistent system. The AHTR employs plate type coated particle fuel assemblies with rapid, off-line refueling. Neutronic analysis of the core has confirmed the viability of a 6-month 2-batch cycle with 9 weight-percent enriched uranium fuel. Refueling is intended to be performed automatically under visual guidance using dedicated robotic manipulators. The present design intent is for used fuel to be stored inside of containment for at least 6 months and then transferred to local dry wells for intermediate term, on-site storage. The mechanical and structural concept development effort has included an emphasis on transportation and constructability to minimize construction costs and schedule. The design intent is that all components be factory fabricated into rail transportable modules that are assembled into subsystems at an on-site workshop prior to being lifted into position using a heavy-lift crane in an open-top style construction. While detailed accident identification and response sequence analysis has yet to be performed, the design concept incorporates multiple levels of radioactive material containment including fully passive responses to all identified design basis or non-very-low frequency beyond design basis accidents. Key building design elements include: 1) below grade siting to minimize vulnerability to aircraft impact, 2) multiple natural circulation decay heat rejection chimneys, 3) seismic base isolation, and 4) decay heat powered back-up electricity generation. The report provides a preconceptual design of the manipulators, the fuel transfer system, and the salt transfer loops. The mechanical handling of the fuel and how it is accomplished without instrumentation inside the salt is described within the report. All drives for the manipulators reside outside the reactor top flange. The design has also taken into account the transportability of major components and how they will be assembled on sit

Pre-Conceptual Design of a Fluoride-Salt-Cooled Small Modular Advanced High Temperature Reactor (SmAHTR)

This document presents the results of a study conducted at Oak Ridge National Laboratory during 2010 to explore the feasibility of small modular fluoride salt-cooled high temperature reactors (FHRs). A preliminary reactor system concept, SmATHR (for Small modular Advanced High Temperature Reactor) is described, along with an integrated high-temperature thermal energy storage or salt vault system. The SmAHTR is a 125 MWt, integral primary, liquid salt cooled, coated particle-graphite fueled, low-pressure system operating at 700 C. The system employs passive decay heat removal and two-out-of-three , 50% capacity, subsystem redundancy for critical functions. The reactor vessel is sufficiently small to be transportable on standard commercial tractor-trailer transport vehicles. Initial transient analyses indicated the transition from normal reactor operations to passive decay heat removal is accomplished in a manner that preserves robust safety margins at all times during the transient. Numerous trade studies and trade-space considerations are discussed, along with the resultant initial system concept. The current concept is not optimized. Work remains to more completely define the overall system with particular emphasis on refining the final fuel/core configuration, salt vault configuration, and integrated system dynamics and safety behavior

Bone Marrow–Harvesting Technique Influences Functional Heterogeneity of Mesenchymal Stem/Stromal Cells and Cartilage Regeneration

Background: Connective tissue progenitors (CTPs) from native bone marrow (BM) or their culture-expanded progeny, often referred to as mesenchymal stem/stromal cells, represents a promising strategy for treatment of cartilage injuries. But the cartilage regeneration capacity of these cells remains unpredictable because of cell heterogeneity. Hypothesis: The harvest technique of BM may highly influence stem cell heterogeneity and, thus, cartilage formation because these cells have distinct spatial localization within BM from the same bone. Study Design: Controlled laboratory study. Methods: CTPs obtained from the femur of patients undergoing total hip replacement by 2 harvest techniques—BM aspiration and BM collection—after bone rasping were immunophenotyped by flow cytometry and evaluated for chondrogenic ability. The spatial localization of different CTP subsets in BM was verified by immunohistochemistry. Results: Cells from the BM after rasping were significantly more chondrogenic than the donor-matched aspirate, whereas no notable difference in their osteogenic or adipogenic potential was observed. The authors then assessed whether distinct immunophenotypically defined CTP subsets were responsible for the different chondrogenic capacity. Cells directly isolated from BM after rasping contained a higher percentage (mean, 7.2-fold) of CD45–CD2711CD561 CTPs as compared with BM aspirates. The presence of this subset in the harvested BM strongly correlated with chondrogenic ability, showing that CD2711CD561 cells are enriched in chondroprogenitors. Furthermore, evaluation of these CTP subsets in BM revealed that CD2711CD561 cells were localized in the bone-lining regions whereas CD2711CD56– cells were found in the perivascular regions. Since the iliac crest remains a frequent site of BM harvest for musculoskeletal regeneration, the authors also compared the spatial distribution of these subsets in trabeculae of femoral head and iliac crest and found CD2711CD561 bone-lining cells in both tissues. Conclusion: Chondrogenically distinct CTP subsets have distinct spatial localization in BM; hence, the harvest technique of BM determines the efficiency of cartilage formation. Clinical Relevance: The harvest technique of BM may be of major importance in determining the clinical success of BM mesenchymal stem/stromal cells in cartilage repair

Pre-Conceptual Design of a Fluoride-Salt-Cooled Small Modular Advanced High Temperature Reactor (SmAHTR)

This document presents the results of a study conducted at Oak Ridge National Laboratory during 2010 to explore the feasibility of small modular fluoride salt-cooled high temperature reactors (FHRs). A preliminary reactor system concept, SmATHR (for Small modular Advanced High Temperature Reactor) is described, along with an integrated high-temperature thermal energy storage or salt vault system. The SmAHTR is a 125 MWt, integral primary, liquid salt cooled, coated particle-graphite fueled, low-pressure system operating at 700 C. The system employs passive decay heat removal and two-out-of-three , 50% capacity, subsystem redundancy for critical functions. The reactor vessel is sufficiently small to be transportable on standard commercial tractor-trailer transport vehicles. Initial transient analyses indicated the transition from normal reactor operations to passive decay heat removal is accomplished in a manner that preserves robust safety margins at all times during the transient. Numerous trade studies and trade-space considerations are discussed, along with the resultant initial system concept. The current concept is not optimized. Work remains to more completely define the overall system with particular emphasis on refining the final fuel/core configuration, salt vault configuration, and integrated system dynamics and safety behavior

AUTOMATED FUEL DESIGN OPTIMIZATION FOR HIGH FLUX ISOTOPE REACTOR LOW ENRICHED URANIUM CORE DESIGN

The low enriched uranium (LEU) conversion project for the High Flux Isotope Reactor (HFIR) requires that the converted core design perform as well as or better than the current high enriched uranium core design with respect to key performance metrics, such as isotope production, while maintaining sufficient safety margins. Various designs and fuel shapes have been explored in previous optimization studies. A suite of scripts has been developed for HFIR LEU design and analysis to simplify the reactor physics and thermal hydraulics (TH) analyses. The scripts include generating a high-fidelity 3D HFIR model to perform core depletion simulations with the SHIFT Monte Carlo code, performing an essential rod criticality search during depletion, parsing SHIFT output to determine HFIR key metrics, and performing TH analysis with the HFIR Steady-State Heat Transfer Code. Previously, these scripts were separated and required human interaction between simulation stages. These scripts have been modernized and integrated into a single Python package (the Python HFIR Analysis and Measurement Engine or PHAME) to streamline execution and avoid potential human error. After modernizing the suite of scripts into a single, automated workflow, the tool set was wrapped into an in-house metaheuristic optimization driver that enables different optimization methods, such as simulated annealing and particle swarm. The optimization driver samples a fuel shape, runs PHAME, calculates the cost function with the metrics returned from PHAME, and repeats those steps until it finds an optimal fuel shape. This work demonstrates the workflow of a comprehensive, automated reactor design study and how metaheuristic optimization methods can be leveraged to fine-tune a design parameter like fuel shape. This workflow of wrapping an optimization driver on a full-scale reactor analysis suite increases design and analysis efficiency

AUTOMATED FUEL DESIGN OPTIMIZATION FOR HIGH FLUX ISOTOPE REACTOR LOW ENRICHED URANIUM CORE DESIGN

The low enriched uranium (LEU) conversion project for the High Flux Isotope Reactor (HFIR) requires that the converted core design perform as well as or better than the current high enriched uranium core design with respect to key performance metrics, such as isotope production, while maintaining sufficient safety margins. Various designs and fuel shapes have been explored in previous optimization studies. A suite of scripts has been developed for HFIR LEU design and analysis to simplify the reactor physics and thermal hydraulics (TH) analyses. The scripts include generating a high-fidelity 3D HFIR model to perform core depletion simulations with the SHIFT Monte Carlo code, performing an essential rod criticality search during depletion, parsing SHIFT output to determine HFIR key metrics, and performing TH analysis with the HFIR Steady-State Heat Transfer Code. Previously, these scripts were separated and required human interaction between simulation stages. These scripts have been modernized and integrated into a single Python package (the Python HFIR Analysis and Measurement Engine or PHAME) to streamline execution and avoid potential human error. After modernizing the suite of scripts into a single, automated workflow, the tool set was wrapped into an in-house metaheuristic optimization driver that enables different optimization methods, such as simulated annealing and particle swarm. The optimization driver samples a fuel shape, runs PHAME, calculates the cost function with the metrics returned from PHAME, and repeats those steps until it finds an optimal fuel shape. This work demonstrates the workflow of a comprehensive, automated reactor design study and how metaheuristic optimization methods can be leveraged to fine-tune a design parameter like fuel shape. This workflow of wrapping an optimization driver on a full-scale reactor analysis suite increases design and analysis efficiency

Progress Towards a Molten Salt Reactor Experiment Benchmark Evaluation

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