Master of Sciences, Case Western Reserve University, 2017, Clinical Research

It is unknown if long-term mortality after non-cardiac surgery differs by mechanism of myocardial injury. To assess this, 12,882 patients were assessed for cTnT sampling within 96-hours of vascular surgery. On Cox proportional hazards analysis, mortality was higher with any detectable cTnT compared to <0.01 ng/ml; cTnT 0.01-0.029 ng/ml (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.18-2.00), 0.03-0.099 ng/ml (HR 1.86, 95% CI 1.49-2.31), 0.10-0.399 ng/ml (HR 1.83, 95% CI 1.46-2.31), and >=0.40 ng/ml (HR 2.62, 95% CI 2.06-3.32). Compared to normal cTnT, baseline cTnT elevation was associated with increased mortality (HR 1.71, 95% CI 1.31-2.24), as were Type 2 myocardial infarction (MI) (HR 1.88, 95% CI 1.57-2.24), and Type 1 MI (HR 2.56, 95% CI 2.56, 1.82-3.60). Survival did not differ between mechanisms on Kaplan-Meier analysis. In conclusion, any detectable cTnT >=0.01 ng/ml is associated with long-term mortality after non-cardiac surgery, however, mortality is independent of mechanism.

Committee: Venu Menon M.D. (Committee Chair); Wilson Tang M.D. (Advisor); Rory Hachamovitch M.D., M.Sc. (Committee Member) Subjects: Health; Health Care; Medicine

Doctor of Philosophy, Case Western Reserve University, 2011, Physiology and Biophysics

In the first study, a rat model of low myocardial blood flow tested whether post-translational changes to proteins of the thin and thick muscle filaments correlate with decreased cardiac contractility. Following three days of low blood flow, cardiac trabeculae demonstrated a reduction in fractional shortening at rest and a relative decline in fractional shortening when challenged with high dose dobutamine, reflecting reduced energy reserves. Permeabilized fibers from low blood flow hearts demonstrated a decline in maximum force and Ca2+ sensitivity. An examination of sarcomeric proteins by two-dimensional gel electrophoresis, mass spectrometry, and phospho-specific antibodies showed Ser23/24 and Ser43/45 phosphorylation of troponin I (TnI). Total TnI phosphorylation was not different between the groups, but Ser23/24 phosphorylation declined with low blood flow, implying an accompanying increase in Ser43/45 phosphorylation of TnI. These findings suggest that altered TnI function, due to changes in the distribution of phosphorylated sites, is an early contributor to reduced contractility of the heart. Previous studies have reported that high fat feeding in mild to moderate heart failure (HF) results in the preservation of contractile function, suggesting that preventing the switch from fatty acid to glucose metabolism in HF may ameliorate dysfunction. Insulin resistance is one potential mechanism for regulating substrate utilization, and the second study sought to determine whether peripheral and myocardial insulin resistance exists with HF and/or high fat diet. Rats underwent coronary artery ligation (HF) or sham surgery and were randomized to normal chow (NC) or high fat diet (SAT) for eight weeks. HF+SAT showed preserved systolic and diastolic function compared to HF+NC. Glucose tolerance tests revealed peripheral insulin resistance in SHAM+SAT, HF+NC, and HF+SAT compared to SHAM+NC. Positron emission tomography imaging confirmed myocardial insulin resistance only (open full item for complete abstract)

Committee: Margaret Chandler (Advisor); Thomas Nosek (Committee Chair); Colleen Croniger (Committee Member); George Dubyak (Committee Member); Faramarz Ismail-Beigi (Committee Member); Julian Stelzer (Committee Member) Subjects: Physiology

Master of Science, The Ohio State University, 1970, Graduate School

Committee: Not Provided (Other) Subjects:

PhD, University of Cincinnati, 2024, Pharmacy: Pharmaceutical Sciences

There is increasing recognition of the pivotal role of the microbiome in addressing numerous questions about human health and disease. Exploring the role of the microbiome in the gastrointestinal tract and skin – the two largest reservoirs of the human microbiota – can provide valuable insights into the pathology and treatment of various diseases. Our first specific aim was to investigate the translocation of gut bacteria to the heart in a murine model of myocardial infarction (MI). In a novel discovery, we demonstrated that gut bacteria, which permeate into the systemic circulation after myocardial infarction, can colonize and proliferate within the heart, thus uncovering the existence of the heart microbiome. This observation was further validated through various techniques by using E. coli Nissle 1917 (EcN) as a tracer bacterium. Our second aim was directed towards developing a gut microbiome-based therapeutic construct to treat post-MI intestinal hyperpermeability. We engineered EcN to express F. prausnitzii-derived microbial anti-inflammatory molecule (MAM) and investigated its safety, efficacy, and mechanism of action in the MI model. Treatment with our recombinant construct, EcN-MAM, resulted in increased survival, enhanced cardiac function, and decreased cardiac fibrosis compared to the placebo group. As an exploratory aim, we also investigated the potential use of microbiome-based constructs for dermatological applications. We engineered EcN to express shinorine, a natural sunscreen, and evaluated its efficacy in an ex vivo human and porcine skin models of ultraviolet radiation (UVR)-induced DNA damage and a reconstructed human epidermis model of UVR-induced reactive oxygen species (ROS) damage. We found that our developed construct, EcN-SH, was effective in protecting against both UVR-induced DNA damage and ROS damage.

Committee: Nalinikanth Kotagiri Ph.D. (Committee Chair); Pankaj Desai Ph.D. (Committee Member); Zalfa Abdel-Malek Ph.D. (Committee Member); Kevin Li Ph.D. (Committee Member); Kavssery Ananthapadmanabhan ENG.SC.D. (Committee Member) Subjects: Pharmaceuticals

Doctor of Philosophy, University of Akron, 2024, Biomedical Engineering

Myocardial infarction commonly known as heart attack, is a type of cardiovascular disease which occurs when the flow of blood is restricted to a part of the heart muscle for a prolonged period, leading to tissue damage or cell death due to lack of oxygen and nutrients. Several tissue engineering strategies have been implemented to regenerate the damaged cardiac tissue and improve cardiac function post myocardial infarction. One of the most promising strategies for cardiac regeneration is using injectable hydrogels derived from decellularized myocardial tissue. Compared with other natural or synthetic biomaterials, the decellularized cardiac extracellular matrix (ECM) hydrogels provide cardiac- specific microenvironment including ECM composition and biochemical cues which supports the cell attachment, growth, migration, and differentiation. Due to these advantages, decellularized cardiac ECM hydrogels have been widely explored for various cardiac tissue engineering applications. However, as the decellularized myocardial tissue is lyophilized and milled into a powder to form hydrogel, the material properties and the ability to induce angiogenesis (formation of new blood vessels) is greatly affected. To address this issue, we developed a hybrid hydrogel (Fn-cECM) by combining decellularized cardiac ECM hydrogel (cECM) solution and fibrin (Fn) solution and investigated their material properties and evaluated their interactions with therapeutic cells. We observed that the Fn-cECM hybrid hydrogel exhibited enhanced degradation, gelation kinetics and storage modulus compared to the cECM hydrogel. Additionally, we observed significant capillary network formation and angiogenic sprouting for human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs) spheroids. Based on our promising outcomes, we evaluated the feasibility of fabricating granular hydrogels using cECM and Fn-cECM microgels produced via extrusion fragmentation to overcome the limita (open full item for complete abstract)

Committee: Ge Zhang (Advisor); Ge Zhang (Committee Chair); Qin Liu (Committee Member); Hossein Ravanbakhsh (Committee Member); Weinan Xu (Committee Member); Jiang Zhe (Committee Member) Subjects: Biomedical Engineering; Biomedical Research

MS, University of Cincinnati, 2023, Engineering and Applied Science: Biomedical Engineering

Diabetes mellitus is widely acknowledged as one of the most prevalent metabolic diseases, affecting millions of people around the world. In addition to presenting the generally observed metabolic deficiencies, diabetes can also severely impact other body systems by impairing circulation, promoting neuropathy, and stalling the wound healing process. In particular, the cardiovascular system is often affected by diabetic co-pathologies; these can result from both increased inflammation and actual changes in the structure of cardiac tissue. One such cardiac co-pathology is diabetic cardiomyopathy, or DCM. DCM presents primarily as impaired contraction of cardiac muscle in conjunction with progressive fibrosis, which is characterized by increased collagen deposition, increased cardiomyocyte apoptosis, and/or left ventricular hypertrophy. These observed effects are likely due to alterations within the diabetic microenvironment. Additionally, prior studies in the field of diabetic wound healing have shown that the hyperglycemic environment can alter the behavior of vascular cells, thus stalling the healing process in the chronic inflammatory phase. Since diabetic cardiomyopathy has been linked to increased occurrences of myocardial infarction and more severe post-infarct complications, there is a need for better therapeutic options than the currently employed treatment method, which relies solely on basic glycemic control. This study explores the use of a bioengineered RAD16-II (RARADADARARADADA) peptide nanofiber scaffold as a delivery vehicle for exogenous matrix metalloprotease 2 (MMP-2). This injectable scaffold/protein combination is suggested as a potential therapy for the severely fibrotic phenotype associated with diabetic cardiomyopathy since it has been shown that MMP-2 levels are reduced in diabetic cardiac tissue. Furthermore, MMP-2 primarily functions in maintaining the composition of the extracellular matrix by degrading fibrillar collagen; th (open full item for complete abstract)

Committee: Daria Narmoneva Ph.D. (Committee Chair); Stacey Schutte Ph.D. (Committee Member); T. Douglas Mast Ph.D. (Committee Member) Subjects: Biomedical Research

Doctor of Philosophy, The Ohio State University, 2022, Biomedical Sciences

Regenerative medicine has the potential to revolutionize the field of surgical medicine. More specifically, tissue-engineered vascular grafts (TEVGs) offer a promising solution to current challenges associated with the use of synthetic conduits in cardiac diseases. Since its first use in humans back in 1999 numerous advances have been made describing the remodeling, performance, and outcomes of TEVGs; however, the barriers to its widespread adoption remain largely the same. First, there remains a tendency for the lumen of TEVGs to narrow due to excessive tissue formation. Second, an issue broadly implicated within the field of cardiothoracic surgery, is the development of adhesions following repeat operations thus hindering access and function. This dissertation seeks to overcome both issues through the application of novel therapeutic agents. The findings reported further advance mechanistic knowledge of the regenerative process that may one day improve outcomes of associated with tissue engineering.

Committee: Christopher Breuer (Advisor); Philip Binkley (Committee Member); Jeffrey Parvin (Committee Member) Subjects: Biology; Biomedical Engineering; Biomedical Research; Cellular Biology; Medicine

Doctor of Philosophy, Case Western Reserve University, 0, Nursing

Acute myocardial infarction (AMI) remains one of the most common causes of death in the United States and allocates a tremendous amount of healthcare expenditures that go beyond $12 billion annually. Machine learning (ML), a subset of artificial intelligence, has emerged as valuable methodological tool to advance nursing and biomedical research. The ML has shown to build predictive models that allow detection of risk factors, assist in diagnosis, and propose personalized treatments plans that may lead to enhanced patients' outcomes. From this perspective, the purpose of this study was to develop and evaluate the predictive performance of a random forest machine-learning model with a conventional multivariate logistic regression model established to examine the influence of individuals predisposing, enabling, and need factors on health service use outcomes (in-hospital mortality, 30-day readmission) of AMI patients guided by the Andersen Model (2008). The cross-sectional retrospective study utilized the Medical Information Mart for Intensive Care which comprises patients admitted to a large tertiary-level academic center of the Harvard Medical School in Boston, MA. The variables of interest include age, gender, ethnicity, type of insurance, body mass index, existing comorbidities, in-hospital mortality, 30-day readmission. Patients with a primary diagnosis of ST-segment elevation MI and non-ST-segment elevation MI cared for at emergency department or critical care units were included in the study. Predictive models for each health service use outcomes were built using RStudio. There were a total of 1171 AMI patients included in the study, 255 (21.8%) patients with STEMI and 916 (78.2%) patients with NSTEMI. Predictors of in-hospital mortality and 30-day readmission included age and existing comorbidities. The accuracy rate, sensitivity, specificity, and AUC for the random forest models were 68-75%, 72-81%, 41-50%, and 0.58-0.59, respectively. On the other hand, the a (open full item for complete abstract)

Committee: Ronald Hickman Jr., PhD, RN, ACNP-BC, FNAP, FAAN (Committee Chair); Mary Dolansky PhD, RN, FAAN (Committee Member); Nicholas Schiltz PhD (Committee Member); Richard Josephson MD, MS, FACC, FAHA, FACP, FAACVPR (Committee Member) Subjects: Nursing

Master of Science (MS), Wright State University, 2021, Microbiology and Immunology

Cardiomyocytes and macrophages have been found to interact via connexin-43 hemichannels. The role of connexin-43, however, is not fully understood. This study shows that these interactions aid in increasing the membrane potential of cardiomyocytes allowing contraction of the cells. HL-1 cardiomyocytes and RAW 264.7 macrophages in coculture increased expression of connexin-43 compared to cardiomyocytes alone. Co-cultures also increased the fluorescence of Di-8-ANEPPS potentiometric dye indicating an increase in cardiomyocyte membrane potential. Treatment with IL-10 and TGF-beta further increased connexin-43 expression and membrane potential. Treatment with SOCS3 inhibited the effects of TGF-beta and IL-10 while having no effect on its own. Confocal imaging can provide visual evidence of these interactions with image layering, 3D imaging and enhanced color.

Committee: Nancy J. Bigley Ph.D. (Committee Chair); Dawn P. Wooley Ph.D. (Committee Member); Marjorie M. Markopoulos Ph.D. (Committee Member) Subjects: Immunology; Microbiology

Doctor of Philosophy, University of Akron, 2019, Biomedical Engineering

Decellularized myocardial tissue has shown great promise as a biological scaffold for cardiac repair and regeneration. Compared with other natural or synthetic biomaterials, decellularized myocardial tissue provides many benefits including the preservation of cardiac-specific microstructure, ECM composition, and perfusable hierarchical vascular bed, which supports the cell attachment, growth, migration, and differentiation. Because of these advantages, decellularized myocardium has been used to construct engineered myocardial tissue (EMT) at various complexities. However, current EMTs fabricated using decellularized myocardium have not been able to precisely mimic native cardiac tissue in terms of cell density, cell distribution, vasculature, and communications among cells. One of the main technical barriers that researchers are facing is the lack of the effective approaches to recellularize acellular myocardium. To address this issue, we aim to develop an innovative recellularization strategy to facilitate the fabrication of EMT using decellularized porcine myocardial slice (dPMS). In this dissertation, we examined the key variables affecting the interaction between dPMS and reseeded stem cells. We focused on investigating three major recellularization parameters during our strategy development: optimal scaffold thickness, cell source, and seeding method. Based on our results, human mesenchymal stem cells (hMSCs) were chosen to be used as one of the cell sources to promote vascularization. Cardiomyocyte sheet derived from the human induced pluripotent stem cells (hiPSCs) was used to improve cell density and cell-to-cell communications. Bilateral cell seeding method was used to enhance uniform cell distribution throughout the dPMS. The influence of types of stem cells, seeding strategy, and scaffold thickness on cell attachment, infiltration, proliferation, cardiovascular differentiation, and scaffold degradation were thoroughly investigated. Additionally, two innov (open full item for complete abstract)

Committee: Ge Zhang (Advisor); Jiang Zhe (Committee Member); Rebecca Willits (Committee Member); Rouzbeh Amini (Committee Member); Yi Pang (Committee Member) Subjects: Biomedical Engineering

Doctor of Philosophy, Case Western Reserve University, 2019, Clinical Research

Precision medicine, a cutting-edge approach aimed to optimize patient outcomes is considered the future of medicine. A substantial gap towards its widespread use is created by scattered, heterogeneous datasets and lack of standardized methodology to extract data from the electronic health record (EHR). Herein, psoriasis, a chronic inflammatory disease with numerous comorbidities and significant impact on quality of life, is used as a prototypical disease to demonstrate one way of overcoming these barriers. The U.S. healthcare system is changing towards emphasizing quality of care. The American Academy of Dermatology (AAD) is constructing various dermatology-specific quality of care measures. These measures were applied to Encite, a dermatology-specific EHR. While there were several challenges to extracting data from the EHR, arguably the largest challenge faced is the provider adherence to recording these proposed quality of care measures. Psoriasis is associated with an increased risk for major adverse cardiac events (MACE; i.e., myocardial infarction (MI), atrial fibrillation (AF), and chronic heart failure (CHF)). Red cell distribution width (RDW) and mean platelet volume (MPV) are readily available clinical tests, and postulated markers for MACE. To examine the association between psoriasis and RDW, MPV and MACE, the aggregate electronic database Explorys was used. The prevalence of MI, AF, and CHF was highest among patients with both elevated RDW and MPV, followed by patients with high RDW and normal MPV. RDW elevation among psoriatic arthritis (PsA) patients was associated with greater odds of MI, AF, and CHF. Potentially, RDW and MPV testing is a cost-effective measure for identifying psoriasis and PsA patients at increased risk of MACE. Furthermore, in a local cohort, the majority of patients with high RDW also had elevated circulating resistin. Among a small patient subset with elevated RDW at baseline, who were followed for a year, response to therap (open full item for complete abstract)

Committee: Douglas Einstadter (Committee Chair); Kevin Cooper (Advisor); Wilma Bergfeld (Committee Member); Dana Crawford (Committee Member); Siran Koroukian (Committee Member) Subjects: Bioinformatics; Biostatistics; Epidemiology; Health Care; Medicine

Doctor of Engineering, Cleveland State University, 2018, Washkewicz College of Engineering

The intrinsic repair mechanism of human heart is not sufficient to overcome the impact placed by adverse pathological conditions, such as myocardial infarction (MI). Current clinical approaches have played significant role in reducing the mortality rate; however, these approaches do not replace the lost cells and tissues of the myocardium. Human bone marrow-derived mesenchymal stem cells (BM-MSCs) are gaining attention in cardiac therapy due to their ability to differentiate into cardiomyocyte like cells and release a wide repertoire of paracrine factors. However, clinical trials of longer duration have shown mixed results in improving cardiac functions. In addition, in-depth studies on the secretome profile of MSCs/ differentiated MSCs and optimal approaches to modulate their outcomes are still lacking. Hence, in the first project of this study, we investigated the role of cell-cell interactions (MSC spheroids), cell-matrix interactions (collagen concentration, topography) and cell-signaling cues [5-azacytidine (aza)] on the cardiac differentiation of BM-MSCs. We found that collagen hydrogel (2 mg/ml), in the presence of 10 µM of aza, offered higher cell survival and caused time-dependent cardiomyogenic evolution of MSC spheroids. We also identified that canonical Wnt/ß-catenin signaling pathway primarily mediated the observed benefits of aza on cardiac differentiation of MSC spheroids. In the second project, we quantified the secretome profile and matrix synthesis by collagen gel-laden BM-MSC spheroids, under optimized culture conditions from the first project, and extended our investigation to MSC spheroids within human fibroblasts-derived collagen. Human collagen promoted higher matrix synthesis over time but severely impacted cell proliferation. The release of inflammatory cytokines was drastically reduced with spheroid formation and collagen cultures, specifically within human collagen. In the last project, we examined the influence of adult human cardiomyocyt (open full item for complete abstract)

Committee: Chandra Kothapalli (Committee Chair); Moo-Yeal Lee (Committee Member); Nolan B. Holland (Committee Member); Mekki Bayachou (Committee Member); Anand Ramamurthi (Committee Member) Subjects: Biomedical Engineering

PHD, Kent State University, 2018, College of Arts and Sciences / School of Biomedical Sciences

ABSTRACT Ischemic heart disease (IHD) is the major underlying cause of myocardial infarction (MI), scarring, and hypertrophy leading to heart failure which is one of the leading causes of death. Cardiac remodeling following induced pressure overload/myocardial infarction is a multiphase reparative process which involves replacement of damaged tissue with physiological (reparative) fibrosis to form scar that limit the expansion of the left ventricle/infarct of the heart. Although therapeutic approaches targeting soluble factor (ex: ACE inhibitors, ARBs, TGF-ß inhibitors: Pirfenidone, Halofuginone) signaling is available for the treatment of cardiac fibrosis and hypertrophy, they showed modest efficacy in clinics. Hence, it is indispensable to identify and develop an alternate and novel therapeutics to treat the heart failure. Mechanical cues are indeed necessary to integrate with soluble factor associated signaling to maintain cardiac physiological functions. Of late, TRPV4 has been shown to be mechanosensor and our lab has established that TRPV4 is a key mechanosensor in endothelial cells and cardiac fibroblasts (CF) and plays an important role in cardiovascular pathophysiology. We have recently demonstrated that TRPV4 mediates cardiac fibroblast differentiation into myofibroblasts in vitro. However, the physiological significance of TRPV4 in cardiac remodeling in vivo is not known. Based on our previous findings, we hypothesized that targeting TRPV4 may offer cardioprotection following pressure overload-induced hypertrophy and myocardial infarction. The first aim of the dissertation was to determine whether TRPV4 mediated mechanotransduction preserves the heart integrity and reduce fibrosis in vivo following pressure overload-induced hypertrophy. By inducing pressure overload hypertrophy (TAC), we found that TRPV4 knockout (KO) mice exhibited improved cardia function, decreased myocardial cross sectional area and left ventricular mass when compared with WT. Furt (open full item for complete abstract)

Committee: CHARLES THODETI PH.D. (Advisor); WILLIAM CHILIAN PH.D (Committee Member); LIYA YIN PH.D (Committee Member); MOSES OYEWUMI PH.D (Committee Member); GARY KOSKI PH.D (Committee Member) Subjects: Biology; Biomedical Research

Doctor of Philosophy, The Ohio State University, 1986, Graduate School

Committee: Not Provided (Other) Subjects: Education

Doctor of Philosophy, The Ohio State University, 1984, Graduate School

Committee: Not Provided (Other) Subjects: Biology

Doctor of Philosophy, The Ohio State University, 1983, Graduate School

Committee: Not Provided (Other) Subjects: Biology

Doctor of Philosophy, The Ohio State University, 1972, Graduate School

Committee: Not Provided (Other) Subjects: Education

Doctor of Philosophy, The Ohio State University, 1971, Graduate School

Committee: Not Provided (Other) Subjects: Health Sciences

MS, University of Cincinnati, 2016, Engineering and Applied Science: Biomedical Engineering

Diabetes mellitus is widely acknowledged as one of the most prevalent metabolic diseases, affecting millions of people around the world. In addition to presenting the generally observed metabolic deficiencies, diabetes can also severely impact other body systems by impairing circulation, promoting neuropathy, and stalling the wound healing process. In particular, the cardiovascular system is often affected by diabetic co-pathologies; these can result from both impaired circulation and actual changes in the structure of cardiac tissue. One such cardiac co-pathology is diabetic cardiomyopathy, or DCM. DCM presents primarily as impaired contraction of cardiac muscle in conjunction with progressive fibrosis, which is characterized by increased collagen deposition, increased cardiomyocyte apoptosis, and/or left ventricular hypertrophy. These observed effects are likely due to alterations within the diabetic microenvironment. Additionally, prior studies in the field of diabetic wound healing have shown that the hyperglycemic environment can alter the behavior of vascular cells, thus stalling the healing process in the chronic inflammatory phase. Since diabetic cardiomyopathy has been linked to increased occurrences of myocardial infarction and more severe post-infarct complications, there is a need for better therapeutic options than the currently employed treatment method, which relies solely on basic glycemic control. This study explores the use of a bioengineered RAD16-II peptide nanofiber scaffold as a delivery vehicle for exogenous matrix metalloprotease 2 (MMP-2). This injectable scaffold/protein combination is suggested as a potential therapy for the severely fibrotic phenotype associated with diabetic cardiomyopathy since it has been shown that MMP-2 levels are reduced in diabetic cardiac tissue. Furthermore, MMP-2 primarily functions in maintaining the composition of the extracellular matrix by degrading fibrillar collagen; thus, decreased MMP-2 levels co (open full item for complete abstract)

Committee: Daria Narmoneva Ph.D. (Committee Chair); Christy Holland Ph.D. (Committee Member); Jo El Schultz Ph.D. (Committee Member) Subjects: Biomedical Research

MS, Kent State University, 2015, College of Arts and Sciences / School of Biomedical Sciences

Ischemic heart disease (IHD) is the leading cause of death worldwide accounting for approximately 7,249,000 deaths representing 12.7% of the total global mortality in a given year. The condition arises when the cardiac muscle's demand for oxygen and nutrients becomes greater than the supply resulting in an ischemic episode. This event is most commonly described as a Myocardial Infarction (MI) or heart attack. The imbalance of supply and demand leads to an area of injury in which the contractile unit of the heart loses proper function leading to a decrease in left ventricular output, pulmonary edema, systemic edema and ultimately heart failure. In the absence of effective endogenous repair mechanisms, stem cell therapy has become an attractive method for regenerating this damaged tissue and improving cardiac function post-MI. Large portions of stem cells do not survive transplantation, but for those that do and successfully reach the area of infarct, there is a clear increase in cardiac function. What remains unclear is exactly how these stem cells are aiding in cardiac regeneration. The stem cells may be creating a microenvironment conducive to regeneration. However, it is also possible that the stem cells are taking cues from the hostile, ischemic microenvironment and differentiating and replacing the damaged cell types resulting in tissue regeneration. In an in vitro model, we aim to examine whether or not an induced pluripotent stem cell (iPSC) will respond to cues within its environment and differentiate into the cell that has supplied that cue. By doing so, we hope to say something about the interaction between stem cells and the hostile microenvironment of an infarct zone. In aim 1, we demonstrate the ability of secretome derived from rat aortic endothelial cells to differentiate iPS cells into endothelial cells. Conditioned media (CM) was collected from EC (EC-CM) over a 24 hr. time period under normoxic conditions. iPS cells were then treated wi (open full item for complete abstract)

Committee: William Chilian Ph.D. (Advisor); Liya Yin M.D., Ph.D. (Committee Member); Feng Dong M.D., Ph.D. (Committee Member); Charles Thodeti Ph.D. (Committee Member) Subjects: Biology; Biomedical Research