51,778 research outputs found
Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches
The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or
insult, a specialised group of facultative lung progenitors become activated to replenish damaged
tissue through a reparative process called regeneration. Disruption in this process results in healing by
fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration
leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and
idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem
cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent
studies provide exciting and novel insights into postnatal lung development and post-injury lung
regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem
cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their
regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue
engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold
and stem cells is now becoming reality. In this review, we will highlight the advancement of our
understanding in lung regeneration and development of stem cell mediated therapeutic strategies in
combating incurable lung diseases
Lung Regeneration: Endogenous and Exogenous Stem Cell Mediated Therapeutic Approaches
The tissue turnover of unperturbed adult lung is remarkably slow. However, after injury or insult, a specialised group of facultative lung progenitors become activated to replenish damaged tissue through a reparative process called regeneration. Disruption in this process results in healing by fibrosis causing aberrant lung remodelling and organ dysfunction. Post-insult failure of regeneration leads to various incurable lung diseases including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. Therefore, identification of true endogenous lung progenitors/stem cells, and their regenerative pathway are crucial for next-generation therapeutic development. Recent studies provide exciting and novel insights into postnatal lung development and post-injury lung regeneration by native lung progenitors. Furthermore, exogenous application of bone marrow stem cells, embryonic stem cells and inducible pluripotent stem cells (iPSC) show evidences of their regenerative capacity in the repair of injured and diseased lungs. With the advent of modern tissue engineering techniques, whole lung regeneration in the lab using de-cellularised tissue scaffold and stem cells is now becoming reality. In this review, we will highlight the advancement of our understanding in lung regeneration and development of stem cell mediated therapeutic strategies in combating incurable lung diseases
The Feasibility of Imaging Myocardial Ischemic/Reperfusion Injury Using \u3csup\u3e99m\u3c/sup\u3eTc-labeled Duramycin in a Porcine Model
When pathologically externalized, phosphatidylethanolamine (PE) is a potential surrogate marker for detecting tissue injuries. 99mTc-labeled duramycin is a peptide-based imaging agent that binds PE with high affinity and specificity. The goal of the current study was to investigate the clearance kinetics of 99mTc-labeled duramycin in a large animal model (normal pigs) and to assess its uptake in the heart using a pig model of myocardial ischemia–reperfusion injury.
Methods
The clearance and distribution of intravenously injected 99mTc-duramycin were characterized in sham-operated animals (n = 5). In a closed chest model of myocardial ischemia, coronary occlusion was induced by balloon angioplasty (n = 9). 99mTc-duramycin (10–15 mCi) was injected intravenously at 1 hour after reperfusion. SPECT/CT was acquired at 1 and 3 hours after injection. Cardiac tissues were analyzed for changes associated with acute cellular injuries. Autoradiography and gamma counting were used to determine radioactivity uptake. For the remaining animals, 99mTc-tetrafosamin scan was performed on the second day to identify the infarct site.
Results
Intravenously injected 99mTc-duramycin cleared from circulation predominantly via the renal/urinary tract with an α-phase half-life of 3.6 ± 0.3 minutes and β-phase half-life of 179.9 ± 64.7 minutes. In control animals, the ratios between normal heart and lung were 1.76 ± 0.21, 1.66 ± 0.22, 1.50 ± 0.20 and 1.75 ± 0.31 at 0.5, 1, 2 and 3 hours post-injection, respectively. The ratios between normal heart and liver were 0.88 ± 0.13, 0.80 ± 0.13, 0.82 ± 0.19 and 0.88 ± 0.14. In vivo visualization of focal radioactivity uptake in the ischemic heart was attainable as early as 30 min post-injection. The in vivo ischemic-to-normal uptake ratios were 3.57 ± 0.74 and 3.69 ± 0.91 at 1 and 3 hours post-injection, respectively. Ischemic-to-lung ratios were 4.89 ± 0.85 and 4.93 ± 0.57; and ischemic-to-liver ratios were 2.05 ± 0.30 to 3.23 ± 0.78. The size of 99mTc-duramycin positive myocardium was qualitatively larger than the infarct size delineated by the perfusion defect in 99mTc-tetrafosmin uptake. This was consistent with findings from tissue analysis and autoradiography.
Conclusion
99mTc-duramycin was demonstrated, in a large animal model, to have suitable clearance and biodistribution profiles for imaging. The agent has an avid target uptake and a fast background clearance. It is appropriate for imaging myocardial injury induced by ischemia/reperfusion
Extracellular Matrix Aggregates from Differentiating Embryoid Bodies as a Scaffold to Support ESC Proliferation and Differentiation
Embryonic stem cells (ESCs) have emerged as potential cell sources for tissue engineering and regeneration owing to its virtually unlimited replicative capacity and the potential to differentiate into a variety of cell types. Current differentiation strategies primarily involve various growth factor/inducer/repressor concoctions with less emphasis on the substrate. Developing biomaterials to promote stem cell proliferation and differentiation could aid in the realization of this goal. Extracellular matrix (ECM) components are important physiological regulators, and can provide cues to direct ESC expansion and differentiation. ECM undergoes constant remodeling with surrounding cells to accommodate specific developmental event. In this study, using ESC derived aggregates called embryoid bodies (EB) as a model, we characterized the biological nature of ECM in EB after exposure to different treatments: spontaneously differentiated and retinoic acid treated (denoted as SPT and RA, respectively). Next, we extracted this treatment-specific ECM by detergent decellularization methods (Triton X-100, DOC and SDS are compared). The resulting EB ECM scaffolds were seeded with undifferentiated ESCs using a novel cell seeding strategy, and the behavior of ESCs was studied. Our results showed that the optimized protocol efficiently removes cells while retaining crucial ECM and biochemical components. Decellularized ECM from SPT EB gave rise to a more favorable microenvironment for promoting ESC attachment, proliferation, and early differentiation, compared to native EB and decellularized ECM from RA EB. These findings suggest that various treatment conditions allow the formulation of unique ESC-ECM derived scaffolds to enhance ESC bioactivities, including proliferation and differentiation for tissue regeneration applications. © 2013 Goh et al
A Survey on Deep Learning in Medical Image Analysis
Deep learning algorithms, in particular convolutional networks, have rapidly
become a methodology of choice for analyzing medical images. This paper reviews
the major deep learning concepts pertinent to medical image analysis and
summarizes over 300 contributions to the field, most of which appeared in the
last year. We survey the use of deep learning for image classification, object
detection, segmentation, registration, and other tasks and provide concise
overviews of studies per application area. Open challenges and directions for
future research are discussed.Comment: Revised survey includes expanded discussion section and reworked
introductory section on common deep architectures. Added missed papers from
before Feb 1st 201
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