6 results on '"Ardehali R"'
Search Results
2. Heart Regeneration by Endogenous Stem Cells and Cardiomyocyte Proliferation: Controversy, Fallacy, and Progress.
- Author
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He L, Nguyen NB, Ardehali R, and Zhou B
- Subjects
- Animals, Cell Culture Techniques, Cell Differentiation, Cell Proliferation genetics, Humans, Proto-Oncogene Proteins c-kit genetics, Proto-Oncogene Proteins c-kit metabolism, Regenerative Medicine, Heart, Myocytes, Cardiac metabolism, Regeneration, Stem Cells cytology, Stem Cells metabolism
- Abstract
Ischemic heart disease is the leading cause of death worldwide. Myocardial infarction results in an irreversible loss of cardiomyocytes with subsequent adverse remodeling and heart failure. Identifying new sources for cardiomyocytes and promoting their formation represents a goal of cardiac biology and regenerative medicine. Within the past decade, many types of putative cardiac stem cells (CSCs) have been reported to regenerate the injured myocardium by differentiating into new cardiomyocytes. Some of these CSCs have been translated from bench to bed with reported therapeutic effectiveness. However, recent basic research studies on stem cell tracing have begun to question their fundamental biology and mechanisms of action, raising serious concerns over the myogenic potential of CSCs. We review the history of different types of CSCs within the past decade and provide an update of recent cell tracing studies that have challenged the origin and existence of CSCs. In addition to the potential role of CSCs in heart regeneration, proliferation of preexisting cardiomyocytes has recently gained more attention. This review will also evaluate the methodologic and technical aspects of past and current studies on CSCs and cardiomyocyte proliferation, with emphasis on technical strengths, advantages, and potential limitations of research approaches. While our understanding of cardiomyocyte generation and regeneration continues to evolve, it is important to address the shortcomings and inaccuracies in this field. This is best achieved by embracing technological advancements and improved methods to label single cardiomyocytes/progenitors and accurately investigate their developmental potential and fate/lineage commitment.
- Published
- 2020
- Full Text
- View/download PDF
3. Multiscale light-sheet for rapid imaging of cardiopulmonary system.
- Author
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Ding Y, Ma J, Langenbacher AD, Baek KI, Lee J, Chang CC, Hsu JJ, Kulkarni RP, Belperio J, Shi W, Ranjbarvaziri S, Ardehali R, Tintut Y, Demer LL, Chen JN, Fei P, Packard RRS, and Hsiai TK
- Subjects
- Animals, Animals, Newborn, Embryo, Nonmammalian, Heart embryology, Heart growth & development, Imaging, Three-Dimensional instrumentation, Intravital Microscopy instrumentation, Light, Microscopy, Fluorescence instrumentation, Microscopy, Fluorescence methods, Models, Animal, Morphogenesis, Respiratory System embryology, Respiratory System growth & development, Time-Lapse Imaging instrumentation, Time-Lapse Imaging methods, Heart diagnostic imaging, Imaging, Three-Dimensional methods, Intravital Microscopy methods, Respiratory System diagnostic imaging
- Abstract
The ability to image tissue morphogenesis in real-time and in 3-dimensions (3-D) remains an optical challenge. The advent of light-sheet fluorescence microscopy (LSFM) has advanced developmental biology and tissue regeneration research. In this review, we introduce a LSFM system in which the illumination lens reshapes a thin light-sheet to rapidly scan across a sample of interest while the detection lens orthogonally collects the imaging data. This multiscale strategy provides deep-tissue penetration, high-spatiotemporal resolution, and minimal photobleaching and phototoxicity, allowing in vivo visualization of a variety of tissues and processes, ranging from developing hearts in live zebrafish embryos to ex vivo interrogation of the microarchitecture of optically cleared neonatal hearts. Here, we highlight multiple applications of LSFM and discuss several studies that have allowed better characterization of developmental and pathological processes in multiple models and tissues. These findings demonstrate the capacity of multiscale light-sheet imaging to uncover cardiovascular developmental and regenerative phenomena.
- Published
- 2018
- Full Text
- View/download PDF
4. Analysis of cardiomyocyte clonal expansion during mouse heart development and injury.
- Author
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Sereti KI, Nguyen NB, Kamran P, Zhao P, Ranjbarvaziri S, Park S, Sabri S, Engel JL, Sung K, Kulkarni RP, Ding Y, Hsiai TK, Plath K, Ernst J, Sahoo D, Mikkola HKA, Iruela-Arispe ML, and Ardehali R
- Subjects
- Animals, Animals, Newborn, Cell Differentiation, Cell Lineage, Cell Proliferation, Embryonic Stem Cells cytology, Female, Fetal Heart cytology, Fetal Heart growth & development, Heart Injuries genetics, Male, Mice, Mice, Transgenic, Myoblasts, Cardiac cytology, Myocardial Infarction genetics, Myocardial Infarction pathology, Myocytes, Cardiac metabolism, Pericardium cytology, Pericardium embryology, Pericardium growth & development, Pregnancy, Sequence Analysis, RNA, Heart growth & development, Heart Injuries pathology, Myocytes, Cardiac cytology
- Abstract
The cellular mechanisms driving cardiac tissue formation remain poorly understood, largely due to the structural and functional complexity of the heart. It is unclear whether newly generated myocytes originate from cardiac stem/progenitor cells or from pre-existing cardiomyocytes that re-enter the cell cycle. Here, we identify the source of new cardiomyocytes during mouse development and after injury. Our findings suggest that cardiac progenitors maintain proliferative potential and are the main source of cardiomyocytes during development; however, the onset of αMHC expression leads to reduced cycling capacity. Single-cell RNA sequencing reveals a proliferative, "progenitor-like" population abundant in early embryonic stages that decreases to minimal levels postnatally. Furthermore, cardiac injury by ligation of the left anterior descending artery was found to activate cardiomyocyte proliferation in neonatal but not adult mice. Our data suggest that clonal dominance of differentiating progenitors mediates cardiac development, while a distinct subpopulation of cardiomyocytes may have the potential for limited proliferation during late embryonic development and shortly after birth.
- Published
- 2018
- Full Text
- View/download PDF
5. Generation of Nkx2-5/CreER transgenic mice for inducible Cre expression in developing hearts.
- Author
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Ranjbarvaziri S, Park S, Nguyen NB, Gilmore WB, Zhao P, and Ardehali R
- Subjects
- Animals, Cell Lineage, Homeobox Protein Nkx-2.5 metabolism, Integrases genetics, Integrases metabolism, Luminescent Proteins genetics, Luminescent Proteins metabolism, Mice, Myocytes, Cardiac cytology, Transgenes, Gene Targeting methods, Genetic Engineering methods, Heart embryology, Homeobox Protein Nkx-2.5 genetics, Myocytes, Cardiac metabolism
- Abstract
Nkx2-5 is a homeobox-containing transcriptional regulator that serves as one of the earliest markers of cardiac lineage commitment. To study the role of Nkx2-5-expressing progenitors at specific time points in cardiac development, we have generated a novel and inducible NKX2-5 mouse line by knocking in a CreER cassette into the Nkx2-5 genomic locus, while preserving the endogenous Nkx2-5 gene to avoid haploinsufficiency. We evaluated the specificity and efficiency of CreER activity after 4-OHT injection by crossing Nkx2-5
CreER/+ mice with a Rosa26tdT/+ reporter strain. Our immunohistochemistry results confirmed Cre-induced tdTomato expression specifically in cells expressing Nkx2-5. These cells were mainly cardiomyocytes and were observed in the embryonic heart as early as day 9.5. Additionally, quantitative polymerase chain reaction on postnatal hearts showed enriched expression of Nkx2-5 in isolated tdTomato-expressing cells. No tdTomato expression was observed in Nkx2-5CreER/+ ;Rosa26tdT/+ mice in the absence of 4-OHT, confirming the inducible nature of CreER activity. The Nkx2-5/CreER mouse model described in this article will serve as an invaluable tool to trace myocardial lineage and to temporally induce genetic manipulation in a selective population of cardiac progenitors during embryonic development and in the adult heart., (© 2017 Wiley Periodicals, Inc.)- Published
- 2017
- Full Text
- View/download PDF
6. Prospective isolation of human embryonic stem cell-derived cardiovascular progenitors that integrate into human fetal heart tissue.
- Author
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Ardehali R, Ali SR, Inlay MA, Abilez OJ, Chen MQ, Blauwkamp TA, Yazawa M, Gong Y, Nusse R, Drukker M, and Weissman IL
- Subjects
- Animals, Biomarkers metabolism, Cell Culture Techniques, Cell Differentiation, Cell Lineage, Cell Separation, Cells, Cultured, Embryonic Stem Cells metabolism, Endothelium, Vascular cytology, Fetus metabolism, Gene Expression Profiling, Gene Expression Regulation, Developmental, Humans, Mesoderm cytology, Mice, Multipotent Stem Cells cytology, Multipotent Stem Cells metabolism, Myocardium cytology, Myocytes, Cardiac metabolism, Myocytes, Smooth Muscle cytology, Myocytes, Smooth Muscle metabolism, Primitive Streak cytology, Receptor Tyrosine Kinase-like Orphan Receptors genetics, Receptor Tyrosine Kinase-like Orphan Receptors metabolism, Receptor, Platelet-Derived Growth Factor alpha genetics, Receptor, Platelet-Derived Growth Factor alpha metabolism, Tissue Survival, Vascular Endothelial Growth Factor Receptor-2 genetics, Vascular Endothelial Growth Factor Receptor-2 metabolism, Embryonic Stem Cells cytology, Fetus cytology, Heart embryology, Myocytes, Cardiac cytology, Myocytes, Cardiac transplantation, Stem Cell Transplantation
- Abstract
A goal of regenerative medicine is to identify cardiovascular progenitors from human ES cells (hESCs) that can functionally integrate into the human heart. Previous studies to evaluate the developmental potential of candidate hESC-derived progenitors have delivered these cells into murine and porcine cardiac tissue, with inconclusive evidence regarding the capacity of these human cells to physiologically engraft in xenotransplantation assays. Further, the potential of hESC-derived cardiovascular lineage cells to functionally couple to human myocardium remains untested and unknown. Here, we have prospectively identified a population of hESC-derived ROR2(+)/CD13(+)/KDR(+)/PDGFRα(+) cells that give rise to cardiomyocytes, endothelial cells, and vascular smooth muscle cells in vitro at a clonal level. We observed rare clusters of ROR2(+) cells and diffuse expression of KDR and PDGFRα in first-trimester human fetal hearts. We then developed an in vivo transplantation model by transplanting second-trimester human fetal heart tissues s.c. into the ear pinna of a SCID mouse. ROR2(+)/CD13(+)/KDR(+)/PDGFRα(+) cells were delivered into these functioning fetal heart tissues: in contrast to traditional murine heart models for cell transplantation, we show structural and functional integration of hESC-derived cardiovascular progenitors into human heart.
- Published
- 2013
- Full Text
- View/download PDF
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