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Cao, Guohua

Publications and source records attributed to Cao, Guohua.

Polymer microfiber meshes facilitate cardiac differentiation of c-kit{sup +} human cardiac stem cells

Electrospun microfiber meshes have been shown to support the proliferation and differentiation of many types of stem cells, but the phenotypic fate of c-kit{sup +} human cardiac stem cells (hCSCs) have not been explored. To this end, we utilized thin (~5 µm) elastomeric meshes consisting of aligned 1.7 µm diameter poly (ester-urethane urea) microfibers as substrates to examine their effect on hCSC viability, morphology, proliferation, and differentiation relative to cells cultured on tissue culture polystyrene (TCPS). The results showed that cells on microfiber meshes displayed an elongated morphology aligned in the direction of fiber orientation, lower proliferation rates, but increased expressions of genes and proteins majorly associated with cardiomyocyte phenotype. The early (NK2 homeobox 5, Nkx2.5) and late (cardiac troponin I, cTnI) cardiomyocyte genes were significantly increased on meshes (Nkx=2.5 56.2±13.0, cTnl=2.9±0.56,) over TCPS (Nkx2.5=4.2±0.9, cTnl=1.6±0.5, n=9, p<0.05 for both groups) after differentiation. In contrast, expressions of smooth muscle markers, Gata6 and myosin heavy chain (SM-MHC), were decreased on meshes. Immunocytochemical analysis with cardiac antibody exhibited the similar pattern of above cardiac differentiation. We conclude that aligned microfiber meshes are suitable for guiding cardiac differentiation of hCSCs and may facilitate stem cell-based therapies for treatment of cardiac diseases. - Highlights: • First study to characterize c-kit{sup +} human cardiac stem cells on microfiber meshes. • Microfiber meshes seem reducing cell proliferation, but no effect on cell viability. • Microfiber meshes facilitate the elongation of human cardiac stem cells in culture. • Cardiac but not smooth muscle differentiation were enhanced on microfiber meshes. • Microfiber meshes may be used as cardiac patches in cell-based cardiac therapy.

60 APPLIED LIFE SCIENCES↗

Pilot study for compact microbeam radiation therapy using a carbon nanotube field emission micro-CT scanner

Purpose: Microbeam radiation therapy (MRT) is defined as the use of parallel, microplanar x-ray beams with an energy spectrum between 50 and 300 keV for cancer treatment and brain radiosurgery. Up until now, the possibilities of MRT have mainly been studied using synchrotron sources due to their high flux (100s Gy/s) and approximately parallel x-ray paths. The authors have proposed a compact x-ray based MRT system capable of delivering MRT dose distributions at a high dose rate. This system would employ carbon nanotube (CNT) field emission technology to create an x-ray source array that surrounds the target of irradiation. Using such a geometry, multiple collimators would shape the irradiation from this array into multiple microbeams that would then overlap or interlace in the target region. This pilot study demonstrates the feasibility of attaining a high dose rate and parallel microbeam beams using such a system. Methods: The microbeam dose distribution was generated by our CNT micro-CT scanner (100μm focal spot) and a custom-made microbeam collimator. An alignment assembly was fabricated and attached to the scanner in order to collimate and superimpose beams coming from different gantry positions. The MRT dose distribution was measured using two orthogonal radiochromic films embedded inside a cylindrical phantom. This target was irradiated with microbeams incident from 44 different gantry angles to simulate an array of x-ray sources as in the proposed compact CNT-based MRT system. Finally, phantom translation in a direction perpendicular to the microplanar beams was used to simulate the use of multiple parallel microbeams. Results: Microbeams delivered from 44 gantry angles were superimposed to form a single microbeam dose distribution in the phantom with a FWHM of 300μm (calculated value was 290 μm). Also, during the multiple beam simulation, a peak to valley dose ratio of ∼10 was found when the phantom translation distance was roughly 4x the beam width. The first prototype CNT-based x-ray tube dedicated to the development of compact MRT technology development was proposed and planned based on the preliminary experimental results presented here and the previous corresponding Monte Carlo simulations. Conclusions: The authors have demonstrated the feasibility of creating microbeam dose distributions at a high dose rate using a proposed compact MRT system. The flexibility of CNT field emission x-ray sources could possibly bring compact and low cost MRT devices to the larger research community and assist in the translational research of this promising new approach to radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Interior micro-CT with an offset detector

Purpose: The size of field-of-view (FOV) of a microcomputed tomography (CT) system can be increased by offsetting the detector. The increased FOV is beneficial in many applications. All prior investigations, however, have been focused to the case in which the increased FOV after offset-detector acquisition can cover the transaxial extent of an object fully. Here, the authors studied a new problem where the FOV of a micro-CT system, although increased after offset-detector acquisition, still covers an interior region-of-interest (ROI) within the object. Methods: An interior-ROI-oriented micro-CT scan with an offset detector poses a difficult reconstruction problem, which is caused by both detector offset and projection truncation. Using the projection completion techniques, the authors first extended three previous reconstruction methods from offset-detector micro-CT to offset-detector interior micro-CT. The authors then proposed a novel method which combines two of the extended methods using a frequency split technique. The authors tested the four methods with phantom simulations at 9.4%, 18.8%, 28.2%, and 37.6% detector offset. The authors also applied these methods to physical phantom datasets acquired at the same amounts of detector offset from a customized micro-CT system. Results: When the detector offset was small, all reconstruction methods showed good image quality. At large detector offset, the three extended methods gave either visible shading artifacts or high deviation of pixel value, while the authors’ proposed method demonstrated no visible artifacts and minimal deviation of pixel value in both the numerical simulations and physical experiments. Conclusions: For an interior micro-CT with an offset detector, the three extended reconstruction methods can perform well at a small detector offset but show strong artifacts at a large detector offset. When the detector offset is large, the authors’ proposed reconstruction method can outperform the three extended reconstruction methods by suppressing artifacts and maintaining pixel values.

62 RADIOLOGY AND NUCLEAR MEDICINE↗