Browsing by Author "Murphy, Michael"

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    Comparison of Biomaterial-Dependent and -Independent Bioprinting Methods for Cardiovascular Medicine
    (Elsevier, 2017) Moldovan, Leni; Babbey, Clifford; Murphy, Michael; Moldovan, Nicanor I.; Department of Biomedical Engineering, School of Engineering and Technology
    There is an increasing need of human organs for transplantation, of alternatives to animal experimentation, and of better in vitro tissue models for drug testing. All these needs create unique opportunities for the development of novel and powerful tissue engineering methods, among which the 3D bioprinting is one of the most promising. However, after decades of incubation, ingenuous efforts, early success and much anticipation, biomaterial-dependent 3D bioprinting, although shows steady progress, is slow to deliver the expected clinical results. For this reason, alternative ‘scaffold-free’ 3D bioprinting methods are developing in parallel at an accelerated pace. In this opinion paper we discuss comparatively the two approaches, with specific examples drawn from the cardiovascular field. Moving the emphasis away from competition, we show that the two platforms have similar goals but evolve in complementary technological niches. We conclude that the biomaterial-dependent bioprinting is better suited for tasks requiring faster, larger, anatomically-true, cell-homogenous and matrix-rich constructs, while the scaffold-free biofabrication is more adequate for cell-heterogeneous, matrix-poor, complex and smaller constructs, but requiring longer preparation time.
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    Contemporary Outcomes of Distal Lower Extremity Bypass for Chronic Limb Threatening Ischemia and a Model Based Comparison with Non-surgical Therapies
    (2021-03) Leckie, Katherin; Bakoyannis, Giorgos; Yiannoutsos, Constantin; Murphy, Michael
    Objective: Gold standard therapy for chronic limb threatening ischemia (CLTI) is revascularization but in patients in whom below-the-knee bypass is indicated autologous vein conduit may not be available. Contemporary outcomes of distal bypass with suboptimal conduits have not been well described and recent advances in non-surgical therapies raise the question of whether in some cases there is evidence that these should be considered. Methods: Data was obtained from the Vascular Quality Initiative (VQI) registry as well as from a multi-center, randomized clinical trial of cell therapy. Incidence of major amputation after distal bypass was estimated for the VQI cohort by conduit type using non-parametric survival analysis with death as a competing risk. A cox proportional hazards model was then fit to the pooled data in a stepwise fashion with death as a competing risk, including evaluations for appropriate transformation, time dependency and interactions for each included covariate, and hazard ratios were estimated for the risk of major amputation by treatment. Results: At 365 days, the estimated cumulative incidence of major amputation with death as a competing risk is 25% after distal bypass with non-autologous biologic conduit (0.2499, 95% CI 0.2242 - 0.2785), 13% for prosthetic (0.1276, 95% CI 0.1172 - 0.1389) and 9% for GSV (0.0900, 95% CI 0.0848 - 0.0956). The cox proportional hazards model found a significant interaction between age and treatment. Compared to bypass with non-autogenous biologic, the hazard ratios for bypass with GSV were 0.41 (p<0.0001), 0.41 (p<0.0001), 0.42 (p<0.0001) and 0.42 (p<0.0001) respectively at ages 55, 60, 65 and 70 and for bypass with prosthetic were 0.68 (p=0.0043), 0.67 (p=0.0004), 0.65 (p<0.0001) and 0.64 (p<0.0001) respectively and for autologous cell therapy 0.22 (p=0.0005), 0.34 (p=0.0011), 0.52 (p=0.0196) and 0.76 (p=0.3677) respectively. No significant differences were found between best medical management and distal bypass with non-autologous biologic. Conclusion: The risk of major amputation after distal bypass is lowest in patients with GSV conduit and highest following bypass with non-autologous biologic. Using a semi-parametric model, cell therapy was estimated to significantly decrease the risk of amputation compared to distal bypass with non-autologous biologic conduit in younger patients.
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    Vascular and Cardiac Adult Stem Cell Therapy Center
    (Office of the Vice Chancellor for Research, 2010-04-09) March, Keith; Murphy, Michael; Petrache, Irina; Evans-Molina, Carmella; Farag, Sherif; Traktuev, Dmitry; Saadatzadeh, Reza; Johnstone, Brian; Schweitzer, Kelly; Rosen, Elliot; Chen, Peng-Sheng
    The mission of the Vascular and Cardiac Adult Stem Cell Therapy Center (VC-CAST) is the discovery and clinical translation of therapies involving transplantation of adult stem cells into patients with debilitating diseases. To accomplish this, VC-CAST fosters multidisciplinary research collaborations that address both biology of adult stem cells that are readily available, and the translation of their study from the laboratory into clinical trials. The use of such cells is highly feasible, and not ethically controversial, as they are derived from readily-available tissues such as fat and bone marrow. Since its inception, VC-CAST projects have been multidisciplinary, involving multiple clinical as well as basic departments of the School of Medicine. VC-CAST projects are also collaborative, with most of the projects having one or more industrial partners. A key partnership has also been established by the creation of the Veterans Affairs Center for Regenerative Medicine (VACRM) at the Roudebush VA Medical Center in Indianapolis, which will provide a unique referral site focusing on research and implementation of first-in-human trials in the fields of poor circulation, arthritis, wound healing, diabetes, and emphysema. Given the focus of VC-CAST researchers on translation, the center is active in pursuit of intellectual property that is critical to building corporate engagement and thus the enablement of translation to clinical trials. Signature center funding has allowed IUPUI investigators to try high-risk, high-reward ideas, which could not otherwise be funded readily, via either NIH or venture-capital methods. Most of these experiments are still ongoing, but have already led to discoveries of potentially critical significance to patients. The novelty of some of these discoveries promises to attract new funding, as well as to provide bases for potential licensing revenues and startup opportunities. This poster will highlight several of these projects, representative of center activities in their collaborative, multidisciplinary and translational and potentially commercializable aspects. Some key projects are as follows: • Based on recent completion of the Phase I/II clinical trial, “Stem cell Angiogenesis to promote limb salVagE (SAVE), a new randomized Phase III clinical trial testing the use of one’s own bone marrow-derived stem cells to save legs from amputation has been initiated, with Dr. Murphy as the national PI. • Adipose Stem Cells for Peripheral Arterial Disease. • Endometrial Regenerative Cells for Peripheral Arterial Disease. • Adipose Stem Cells for treatment of Heart Attack and prevention of Heart Failure. • Adipose Stem Cells for Emphysema and other Lung Diseases • Adipose Stem Cells for Prevention and Treatment of Diabetes • Isolation and Characterization of Endothelial and Mesenchymal Stem Cells from Term Human Placenta. • Isolation and Characterization of Endothelial Colony Forming Cells (ECFCs) from Human Adult Blood Vessels
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    Vascular and Cardiac Adult Stem Cell Therapy Center (VC-CAST)
    (Office of the Vice Chancellor for Research, 2011-04-08) March, Keith; Murphy, Michael; Petrache, Irina; Evans-Molina, Carmella; Traktuev, Dmitry; Johnstone, Brian; Clauss, Matthias; Hong, Soonjun; Gangaraju, Rajashekhar; Saadatzadeh, M. Reza; Schweitzer, Kelly; Rosen, Elliot; Farag, Sherif; Du, Yansheng; Chen, Peng-Sheng
    The mission of the Vascular and Cardiac Adult Stem Cell Therapy Center (VC-CAST) is the discovery and clinical translation of therapies involving transplantation of adult stem cells into patients with debilitating diseases. VC-CAST fosters multidisciplinary research collaborations that address the biology of adult stem cells that are readily available, as well as the translation of their study from the laboratory into clinical trials. The use of such cells is highly feasible, and not ethically controversial, as they are derived from readily-available tissues such as fat and bone marrow. VC-CAST projects involve partners from multiple clinical and basic departments of the School of Medicine. VC-CAST projects are also collaborative externally, with most projects having one or more industrial or academic external partners. A key partnership has also been established at the Roudebush VA Medical Center in Indianapolis by creation of the Veterans Affairs Center for Regenerative Medicine (VACRM), which will provide a unique referral site focusing on research and implementation of first-in-human trials in the fields of poor circulation, stroke, arthritis, wound healing, diabetes, and emphysema. Given the focus on translation, the center is active in pursuit of intellectual property that is critical to building corporate engagement and thus the enablement of translation to clinical trials. Signature Center funding has allowed IUPUI investigators to try high-risk, high-reward ideas, which could not otherwise be funded readily, via either NIH or venture-capital methods. Most of these experiments have already led to discoveries of potentially critical significance to patients. The novelty of some of these discoveries has attracted new funding, as well as provided bases for potential licensing revenues and startup opportunities. This poster will highlight several such projects, representative of center activities in their multidisciplinary, translational, and potentially commercializable aspects. Several key projects are as follows: • Saving Legs from Amputation o Bone Marrow Stem Cells: Based on our completion of the Phase I/II clinical trial, “Stem cell Angiogenesis to promote limb salVagE (SAVE), we have initiated a randomized Phase III clinical trial testing one’s own bone marrow-derived stem cells to save legs from amputation, with Dr. Murphy as national PI. o Fat-derived (Adipose) Stem Cells– we are testing the hypothesis that these are more potent than Bone Marrow-derived stem cells with new funding from a corporate partner as well as the Department of Defense. o Endometrial Regenerative Cells– further extending above efforts, with new NIH funding to study this allogeneic (non-self, “off-the-shelf”) cell type. • Treatment of Heart Attack and prevention of Heart Failure. New data this year shows Adipose Stem Cells protect from heart damage when given systemically. • Treatment of Emphysema and other Lung Diseases. Adipose Stem Cells markedly protect from cigarette smoke-induced emphysema, a generally untreatable condition. • Prevention and Treatment of Diabetes– Adipose Stem Cells can ameliorate diabetes. This work has attracted new Veterans Affairs funding this past year. • Treatment of Parkinson’s Disease by rescue of dopaminergic neurons from death. New funding attracted in the past year by the Signature Center led to preclinical data that extended prior work in stroke models to models of Parkinson’s Disease. These data suggest that the conditioned medium from ASCs can be useful in this debilitating condition, and form the basis for a new NIH application. • Treatment of Diabetic Retinopathy by vascular stabilization using adipose stem cells. This is a new project in the past year, and has generated encouraging early data which is being used in seeking further (external) funding. • Human Placenta as a stem cell source: Isolation and Characterization of Endothelial and Mesenchymal Stem Cells from Term Placenta. • Human Saphenous Vein as a cell source: Isolation and Characterization of Endothelial Colony Forming Cells (ECFCs) from Human Saphenous Vein can form the basis for vascular network formation.