A5005649537- Tissue Engineering and Regenerative Medicine
- Congenital heart defects research
- Electrospun Nanofibers in Biomedical Applications
- Cardiac Fibrosis and Remodeling
- Pluripotent Stem Cells Research
- RNA Research and Splicing
- Cancer Mechanisms and Therapy
- Signaling Pathways in Disease
- RNA modifications and cancer
- Mesenchymal stem cell research
- Molecular Biology Techniques and Applications
- Mechanical Circulatory Support Devices
- Peptidase Inhibition and Analysis
- Mechanisms of cancer metastasis
- Fuel Cells and Related Materials
- Telomeres, Telomerase, and Senescence
- CRISPR and Genetic Engineering
- Pancreatic function and diabetes
- Nuts composition and effects
- MicroRNA in disease regulation
- Transplantation: Methods and Outcomes
- Hippo pathway signaling and YAP/TAZ
- Cardiovascular Function and Risk Factors
- Electrohydrodynamics and Fluid Dynamics
- Virus-based gene therapy research
San Diego State University
2012-2022
Monsanto (United States)
2015-2021
Regenerative Medicine Institute
2019
Sharp Memorial Hospital
2013-2017
Myocardial function is enhanced by adoptive transfer of human cardiac progenitor cells (hCPCs) into a pathologically challenged heart. However, advanced age, comorbidities, and myocardial injury in patients with heart failure constrain the proliferation, survival, regenerative capacity hCPCs. Rejuvenation senescent hCPCs will improve outcome therapy for substantial patient population possessing functionally impaired stem cells.Reverse phenotypic functional senescence ex vivo modification...
The relative actions and synergism between distinct myocardial-derived stem cell populations remain obscure. Ongoing debates on optimal population(s) for treatment of heart failure prompted implementation a protocol isolation multiple from single myocardial tissue sample to develop new insights achieving regeneration.Establish robust cardiac culture consistently generate 3 human biopsy.Isolation endogenous was performed samples routinely discarded during implantation left ventricular assist...
Senescence-associated dysfunction deleteriously affects biological activities of human c-Kit+ cardiac progenitor cells (hCPCs), particularly under conditions in vitro culture. In comparison, preservation self-renewal and decreases mitochondrial reactive oxygen species (ROS) are characteristics murine CPCs vivo that reside within hypoxic niches. Recapitulating niche tension ∼1% O2 for expansion hCPCs rather than typical normoxic cell culture (21% ) could provide significant improvement...
Biological significance of c-Kit as a cardiac stem cell marker and role(s) c-Kit+ cells in myocardial development or response to pathological injury remain unresolved because varied discrepant findings. Alternative experimental models are required contextualize reconcile discordant published observations biology provide meaningful insights regarding clinical relevance signaling for translational therapy.The main objectives this study follows: demonstrating through combined studies both human...
Abstract Cellular therapy to treat heart failure is an ongoing focus of intense research, but progress toward structural and functional recovery remains modest. Engineered augmentation established cellular effectors overcomes impediments enhance reparative activity. Such ‘next generation’ implementation includes delivery combinatorial cell populations exerting synergistic effects. Concurrent isolation expansion three distinct cardiac-derived interstitial types from human tissue, previously...
Autologous stem cell therapy using human c-Kit+ cardiac progenitor cells (hCPCs) is a promising therapeutic approach for treatment of heart failure (HF). However, hCPCs derived from aged patients with HF genetic predispositions and comorbidities chronic diseases exhibit poor proliferative migratory capabilities, which impair overall reparative potential injured myocardium. Therefore, empowering functionally compromised proregenerative molecules ex vivo crucial improving the outcome in HF.To...
Three Chinese chestnut bacterial artificial chromosome (BAC) libraries were developed and used for physical map construction. Specifically, high information content fingerprinting was to assemble 126,445 BAC clones into 1,377 contigs 12,919 singletons. Integration of the dense genetic with achieved via high-throughput hybridization using overgo probes derived from sequence-based markers. A total 1,026 anchored including 831 corresponding 878 expressed sequence tag-based Within map, three...
Abstract Cardiomyocyte ploidy has been described but remains obscure in cardiac interstitial cells. Ploidy of c-kit+ cells was assessed using confocal, karyotypic, and flow cytometric technique. Notable differences were found between rodent (rat, mouse) possessing mononuclear tetraploid (4n) content, compared to large mammals (human, swine) with diploid (2n) content. In-situ analysis, confirmed fresh isolates, revealed content human a mixture mouse. Downregulation the p53 signaling pathway...
Telomere attrition in cardiomyocytes is associated with decreased contractility, cellular senescence, and up-regulation of proapoptotic transcription factors. Pim1 a cardioprotective kinase that antagonizes the aging phenotype delays senescence by maintaining telomere length, but mechanism remains unknown. Another pathway responsible for regulating length transforming growth factor beta (TGFβ) signalling where inhibiting TGFβ maintains length. The relationship between has not been explored....
Autologous cardiac progenitor cell (CPC) therapy is a promising approach for treatment of heart failure (HF). There an unmet need to identify inherent deficits in aged/diseased human CPCs (hCPCs) derived from HF patients the attempts augment their regenerative capacity prior use clinical setting. Here we report significant functional correlations between phenotypic properties hCPCs isolated biopsies patients, parameters and expression P2Y14 purinergic receptor (P2Y14 R), crucial detector...
Abstract Cardiac interstitial cells (CICs) perform essential roles in myocardial biology through preservation of homeostasis as well response to injury or stress. Studies murine CIC reveal remarkable plasticity terms transcriptional reprogramming and ploidy state with important implications for function. Despite over a decade characterization vivo utilization adult c-Kit+ (cCIC), adaptability functional responses upon delivery mammalian hearts remain poorly understood. Limitations...
Existing approaches to modify stem cells for myocardial regeneration desperately need innovative solutions that enhance cell engraftment and persistence. Although this deficiency has been attacked through combinatorial delivery, there is no evidence these injections provide direct cellular crosstalk promote survival proliferation. Therefore, we created a CardioCluster, 3D microenvironment consisting of three defined populations from the human heart: c-kit + cardiac progenitor (CPCs), CD90...
Abstract Cellular therapy to treat heart failure is an ongoing focus of intense research, but with limited progress. Engineered augmentation established cellular effectors overcomes impediments, enhancing reparative activity. Such ‘next generation’ implementation includes delivery combinatorial cell populations working together synergistically. Concurrent isolation and expansion three distinct cardiac-derived interstitial types from human tissue prompted design a 3D structure that maximizes...
Ex vivo expansion of cells is necessary in regenerative medicine to generate large populations for therapeutic use. Adaptation culture conditions prompt an increase transcriptome diversity and decreased population heterogeneity cKit+ cardiac interstitial (cCICs). The "transcriptional memory" influenced by cellular origin remained unexplored likely differ between neonatal versus senescent input undergoing expansion. Transcriptional profiles derived from single cell RNASEQ platforms...
Cellular therapy is an emerging interventional strategy to treat heart failure and has demonstrated tremendous potential in recent years. Use of endogenous stem cells found within the heart, cardiac progenitor (CPC), prompted intense basic research multiple experimental animal models as well clinical trials patients. Scientifically, field continues unravel mechanisms CPC involvement remodeling repair under both normal pathologic conditions. Research been primarily performed mouse models,...
Discovery of endogenous stem cells found within the heart, cardiac progenitor (CPC), has prompted intense basic discovery in multiple experimental animal models and clinical trials heart failure patients. A survey literature reveals or cellular exhibiting regenerative properties are also characterized by genome duplication polyploidization. Our lab recently discovered a fundamental difference between large small mammalian CPCs through karyotype analysis: rodent (rat, mouse) possess...