Person: Campbell, Patrick
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Campbell
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Campbell, Patrick
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Publication Angiotensin II Induced Cardiac Dysfunction on a Chip(Public Library of Science, 2016) Horton, Renita E.; Yadid, Moran; McCain, Megan L.; Sheehy, Sean Paul; Pasqualini, Francesco; Park, Sung-Jin; Cho, Alexander; Campbell, Patrick; Parker, KevinIn vitro disease models offer the ability to study specific systemic features in isolation to better understand underlying mechanisms that lead to dysfunction. Here, we present a cardiac dysfunction model using angiotensin II (ANG II) to elicit pathological responses in a heart-on-a-chip platform that recapitulates native laminar cardiac tissue structure. Our platform, composed of arrays of muscular thin films (MTF), allows for functional comparisons of healthy and diseased tissues by tracking film deflections resulting from contracting tissues. To test our model, we measured gene expression profiles, morphological remodeling, calcium transients, and contractile stress generation in response to ANG II exposure and compared against previous experimental and clinical results. We found that ANG II induced pathological gene expression profiles including over-expression of natriuretic peptide B, Rho GTPase 1, and T-type calcium channels. ANG II exposure also increased proarrhythmic early after depolarization events and significantly reduced peak systolic stresses. Although ANG II has been shown to induce structural remodeling, we control tissue architecture via microcontact printing, and show pathological genetic profiles and functional impairment precede significant morphological changes. We assert that our in vitro model is a useful tool for evaluating tissue health and can serve as a platform for studying disease mechanisms and identifying novel therapeutics.Publication Three-Dimensional Paper-Based Model for Cardiac Ischemia(Wiley-Blackwell, 2014) Mosadegh, Bobak; Dabiri, Borna; Lockett, Matthew; Derda, Ratmir; Campbell, Patrick; Parker, Kevin; Whitesides, GeorgeIn vitro models of ischemia have not historically recapitulated the cellular interactions and gradients of molecules that occur in a 3D tissue. This work demonstrates a paper-based 3D culture system that mimics some of the interactions that occur among populations of cells in the heart during ischemia. Multiple layers of paper containing cells, suspended in hydrogels, are stacked to form a layered 3D model of a tissue. Mass transport of oxygen and glucose into this 3D system can be modulated to induce an ischemic environment in the bottom layers of the stack. This ischemic stress induces cardiomyocytes at the bottom of the stack to secrete chemokines which subsequently trigger fibroblasts residing in adjacent layers to migrate toward the ischemic region. This work demonstrates the usefulness of patterned, stacked paper for performing in vitro mechanistic studies of cellular motility and viability within a model of the laminar ventricle tissue of the heart.Publication Coupling primary and stem cell–derived cardiomyocytes in an in vitro model of cardiac cell therapy(The Rockefeller University Press, 2016) Aratyn-Schaus, Yvonne; Pasqualini, Francesco; Yuan, Hongyan; McCain, Megan L.; Ye, George J.C.; Sheehy, Sean Paul; Campbell, Patrick; Parker, KevinThe efficacy of cardiac cell therapy depends on the integration of existing and newly formed cardiomyocytes. Here, we developed a minimal in vitro model of this interface by engineering two cell microtissues (μtissues) containing mouse cardiomyocytes, representing spared myocardium after injury, and cardiomyocytes generated from embryonic and induced pluripotent stem cells, to model newly formed cells. We demonstrated that weaker stem cell–derived myocytes coupled with stronger myocytes to support synchronous contraction, but this arrangement required focal adhesion-like structures near the cell–cell junction that degrade force transmission between cells. Moreover, we developed a computational model of μtissue mechanics to demonstrate that a reduction in isometric tension is sufficient to impair force transmission across the cell–cell boundary. Together, our in vitro and in silico results suggest that mechanotransductive mechanisms may contribute to the modest functional benefits observed in cell-therapy studies by regulating the amount of contractile force effectively transmitted at the junction between newly formed and spared myocytes.Publication Phototactic guidance of a tissue-engineered soft-robotic ray(American Association for the Advancement of Science (AAAS), 2016) Park, Sung-Jin; Gazzola, Mattia; Park, Kyung; Park, Shirley; Di Santo, Valentina; Blevins, Erin; Lind, Johan; Campbell, Patrick; Dauth, Stephanie; Capulli, Andrew; Pasqualini, Francesco; Ahn, Seungkuk; Cho, Alexander; Yuan, Hongyan; Maoz, Ben; Vijaykumar, Ragu; Choi, Jeong-Woo; Deisseroth, Karl; Lauder, George; Mahadevan, Lakshminarayanan; Parker, KevinInspired by the relatively simple morphological blueprint provided by batoid fish such as stingrays and skates, we create a biohybrid system that enables an artificial animal, a tissue-engineered ray, to swim and phototactically follow a light cue. By patterning dissociated rat cardiac myocytes on an elastomeric body enclosing a microfabricated gold skeleton, we replicated fish morphology at one-tenth scale and captured basic fin deflection patterns of batoid fish. Optogenetics allows for phototactic guidance, steering and turning maneuvers. Optical stimulation induced sequential muscle activation via serpentine patterned muscle circuits leading to coordinated undulatory swimming. The speed and direction of the ray was controlled by modulating light frequency and by independently eliciting right and left fins, allowing the biohybrid machine to maneuver through an obstacle course.