scholarly journals Definition of a cell surface signature for human cardiac progenitor cells after comprehensive comparative transcriptomic and proteomic characterization

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
José Luis Torán ◽  
Juan Antonio López ◽  
Patricia Gomes-Alves ◽  
Susana Aguilar ◽  
Carlos Torroja ◽  
...  
Keyword(s):  
Cell Surface ◽  
Progenitor Cells ◽  
Cardiac Progenitor Cells ◽  
A Cell ◽  
Definition Of ◽  
Surface Signature

Abstract 65: Latrophilin-2 is a Specific Cell-surface Marker for Cardiac Progenitor Cells and Specifies Cardiac Lineage Commitment and Development

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Hyun-Jai Cho ◽  
Choon-Soo Lee ◽  
Jin-Woo Lee ◽  
Jung-Kyu Han ◽  
Han-Mo Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Surface ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Cardiac Development ◽  
Cardiac Differentiation ◽  
Specific Cell ◽  
Specific Marker ◽  
Cardiac Progenitor Cells ◽  
Cardiac Lineage

Backgrounds: The identification of a lineage-specific marker plays a pivotal role in understanding developmental process and is utilized to isolate a certain cell type with high purity for the therapeutic purpose. We here report a new cardiac-specific marker, and demonstrate its functional significance in the cardiac development. Methods and Results: When mouse pluripotent stem cells (ES and iPS cells) were stimulated with BMP4, Activin A, bFGF and VEGF, they differentiated into cardiac cells. To screen cell-surface expressing molecules on cardiac progenitor cells compared to undifferentiated mouse iPS and ES cells, we isolated Flk1+/PDGFRa+ cells at differentiation day 4 and performed microarray analysis. Among candidates, we identified a new G protein-coupled receptor, Latrophilin-2 (LPHN2) whose signaling pathway and its effect on cardiac differentiation is unknown. In sorting experiments under cardiac differentiation condition, LPHN2+ cells derived from pluripotent stem cells strongly expressed cardiac-related genes (Mesp1, Nkx2.5, aMHC and cTnT) and exclusively gave rise to beating cardiomyocytes, as compared with LPHN2- cells. LPHN2-/- mice revealed embryonically lethal and huge defects in cardiac development. Interestingly, LPHN2+/- heterozygotes were alive and fertile. For the purpose of cardiac regeneration, we transplanted iPS-derived LPHN2+ cells into the infarcted heart of adult mice. LPHN2+ cells differentiated into cardiomyocytes, and systolic function of left ventricle was improved and infarct size was reduced. We confirmed LPHN2 expression on human iPS and ES cell-derived cardiac progenitor cells and human heart. Conclusions: We demonstrate that LPHN2 is a functionally significant and cell-surface expressing marker for both mouse and human cardiac progenitor and cardiomyocytes. Our findings provide a valuable tool for isolating cardiac lineage cells from pluripotent stem cells and an insight into cardiac development and regeneration.

P3479Sequential stimulation and inhibition of lysophosphatidic acid receptor 4 are critical for cardiac differentiation and repair

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H J Cho ◽  
J W Lee ◽  
C S Lee ◽  
Y R Ryu ◽  
H S Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Surface ◽  
Progenitor Cells ◽  
Lysophosphatidic Acid ◽  
Functional Significance ◽  
Early Stage ◽  
Cardiac Differentiation ◽  
Cardiac Progenitor Cells ◽  
Acid Receptor ◽  
Downstream Signaling

Abstract Background The clinical application of cell therapy to repair the damaged heart needs to understand the precise differentiation process of stem cells and the characteristics of cardiac progenitor cells. Purpose We examined the cardiac-specific markers that expressed on the cell surface and determined their functional significance during cardiac differentiation. Methods and results We screened cell-surface expressing proteins on cardiac progenitor cells at differentiation day 3 compared to undifferentiated pluripotent stem cells (PSCs). Among candidates, we identified lysophosphatidic acid receptor 4 (LPAR4) that is a G protein-coupled receptor. During in vitro differentiation of mouse PSCs toward cardiac cells, LPAR4 expression peaked for 3–5 days and then and declined immediately. Also in vivo, LPAR4 was specifically expressed in the early stage of heart development in embryos and disappeared completely in adults, suggesting that stimulatory signal of LPAR4 at an early stage should be shut off for further progression of differentiation. We next have identified the LPAR4 downstream signaling molecule, p38MAPK, by comparing PSCs and LPAR4 knockdown PSCs. In both mouse and human PSCs, ODP (LPAR4 specific agonist) followed by p38MAPK blocker (SB203580) treatment significantly increased cardiac differentiation efficiency. Furthermore, we investigated whether LPAR4 is the maker for adult cardiac progenitor cells. We found that LPAR4-positive cells were rarely present in normal adult mouse hearts, but LPAR4-positive cells were increased when the heart was damaged. LPAR4-positive cells from adult hearts differentiated into cardiomyocytes. After myocardial infarction (MI), the sequential stimulation and inhibition of LPAR4 with ODP and p38MAPK blocker resulted in the reduction of infarct size and improvement of left ventricular dysfunction. Conclusion We demonstrated that LPAR4 is a cardiac progenitor-specific marker and its functional significance during cardiac differentiation and regeneration. Our findings provide a new insight in cell-free cardiac repair by the modulation of progenitor-specific downstream signaling. Acknowledgement/Funding Grants from “Strategic Center of Cell and Bio Therapy” (grant number: HI17C2085) and “Korea Research-Driven Hospital” (HI14C1277)

scholarly journals Cardiac Progenitor Cells from Stem Cells: Learning from Genetics and Biomaterials

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1536 ◽  
Author(s):  
Sara Barreto ◽  
Leonie Hamel ◽  
Teresa Schiatti ◽  
Ying Yang ◽  
Vinoj George
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Genetic Factors ◽  
Induced Pluripotent Stem Cell ◽  
Significant Shift ◽  
Cardiac Progenitor Cells ◽  
Recent Developments ◽  
A Cell ◽  
Induced Pluripotent

Cardiac Progenitor Cells (CPCs) show great potential as a cell resource for restoring cardiac function in patients affected by heart disease or heart failure. CPCs are proliferative and committed to cardiac fate, capable of generating cells of all the cardiac lineages. These cells offer a significant shift in paradigm over the use of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes owing to the latter’s inability to recapitulate mature features of a native myocardium, limiting their translational applications. The iPSCs and direct reprogramming of somatic cells have been attempted to produce CPCs and, in this process, a variety of chemical and/or genetic factors have been evaluated for their ability to generate, expand, and maintain CPCs in vitro. However, the precise stoichiometry and spatiotemporal activity of these factors and the genetic interplay during embryonic CPC development remain challenging to reproduce in culture, in terms of efficiency, numbers, and translational potential. Recent advances in biomaterials to mimic the native cardiac microenvironment have shown promise to influence CPC regenerative functions, while being capable of integrating with host tissue. This review highlights recent developments and limitations in the generation and use of CPCs from stem cells, and the trends that influence the direction of research to promote better application of CPCs.

CD34+AC133+VEGFR-2+ Cells Are Primitive Hematopoietic Progenitors, Not Functional Endothelial Progenitor Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1796-1796
Author(s):  
Jamie Case ◽  
Laura E. Mead ◽  
Hilary A. White ◽  
Mohammad R. Saadatzadeh ◽  
Mervin C. Yoder ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cell Surface ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Disease Risk ◽  
Hematopoietic Cell ◽  
Proliferative Potential ◽  
Human Umbilical Cord ◽  
Endothelial Progenitor ◽  
Definition Of

Abstract Endothelial progenitor cells (EPCs) are currently used for angiogenic therapies or as biomarkers to assess cardiovascular disease risk and progression. However, there is no uniform definition of an EPC, which complicates interpretation of prior EPC studies. EPCs are primarily defined by expression of cell surface antigens. The most widely cited definition of an EPC is a cell which co-expresses CD34, AC133 and VEGFR-2. Importantly, these antigens are also expressed on the most primitive population of hematopoietic progenitor cells (HPCs), including high proliferative potential- (HPP-) and low proliferative potential-colony forming cells (LPP-CFCs). Remarkably, CD34+AC133+VEGFR-2+ cells have never been isolated and plated in endothelial cell (EC) or hematopoietic cell clonogenic assays to determine what cell progeny can be derived from a CD34+AC133+VEGFR-2+ cell. Utilizing human umbilical cord blood (CB), an enriched source of both EPCs and HPCs, we isolated and purified CD34+AC133+VEGFR-2+ cells by FACS and assayed for the presence of clonogenic endothelial CFCs (ECFCs) plus HPP- and LPP-CFCs. Surprisingly, CD34+AC133+VEGFR-2+ cells do not form ECFCs under any culture conditions previously described for outgrowth of EPCs. However, consistent with a HPC phenotype, CD34+AC133+VEGFR-2+ cells formed both HPP- and LPP-CFCs in multiple independent assays. In addition, all CD34+AC133+VEGFR-2+ cells were shown to co-express the specific hematopoietic cell surface antigen, CD45, which is not present on ECs. Based on this information, we plated CD34+CD45+ or CD34+CD45− cells to determine if EPCs could be separated from HPCs on the basis of CD45 expression. In multiple independent assays, CD34+CD45+ cells consistently formed both HPP- and LPP-CFCs but not EC colonies. In contrast, CD34+CD45− cells form EC colonies but not hematopoietic cell colonies. Taken together, these data demonstrate that circulating CD34+AC133+VEGFR-2+ cells are HPCs and the biologic mechanism for their correlation with cardiovascular disease needs to be re-examined. Furthermore, studies focused on determining the angiogenic potential of CD34+CD45− cells are needed given that this cell population harbors ECFCs.

Application of high-resolution field-emission LVSEM, backscatter imaging, immunogold staining to definition of the spatial distributions of two human neutrophil adherence receptors

1993 ◽  
Vol 51 ◽  
pp. 36-37
Author(s):  
Robert D. Nelson ◽  
Sharon R. Hasslen ◽  
Stanley L. Erlandsen
Keyword(s):  
Cell Surface ◽  
Surface Membrane ◽  
Three Dimensional ◽  
Human Neutrophils ◽  
Spatial Distributions ◽  
Immunogold Staining ◽  
Functional Control ◽  
Neutrophil Adherence ◽  
Definition Of ◽  
Mode Of Attachment

Receptors are commonly defined in terms of number per cell, affinity for ligand, chemical structure, mode of attachment to the cell surface, and mechanism of signal transduction. We propose to show that knowledge of spatial distribution of receptors on the cell surface can provide additional clues to their function and components of functional control.L-selectin and Mac-1 denote two receptor populations on the neutrophil surface that mediate neutrophil-endothelial cell adherence interactions and provide for targeting of neutrophil recruitment to sites of inflammation. We have studied the spatial distributions of these receptors using LVSEM and backscatter imaging of isolated human neutrophils stained with mouse anti-receptor (primary) antibody and goat anti-mouse (secondary) antibody conjugated to 12 nm colloidal gold. This combination of techniques provides for three-dimensional analysis of the expression of these receptors on different surface membrane domains of the neutrophil: the ruffles and microvilli that project from the cell surface, and the cell body between these projecting structures.

Cardiac progenitor cells in terminally failing hearts: Immunohistological observations in human myocardium

2007 ◽  
Vol 55 (S 1) ◽  
Author(s):  
M Arnold ◽  
V Kufer ◽  
A Schütz ◽  
B Reiter ◽  
M Fittkau ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Human Myocardium ◽  
Cardiac Progenitor Cells

Breakthrough Regenerative Cardiopoietic Stem Cells and Related Technologies in the Field of Cardiovascular Medicine – From Bench to Bedside

2012 ◽  
Vol 7 (1) ◽  
pp. 14
Author(s):  
Christian Homsy ◽  
Keyword(s):  
Stem Cells ◽  
Cell Therapy ◽  
Progenitor Cells ◽  
Cardiac Disease ◽  
Cardiac Tissue ◽  
Cardiac Repair ◽  
Cardiac Diseases ◽  
Cardiac Progenitor Cells ◽  
Biotechnology Company ◽  
Cardiovascular Medicine

The scale of cardiac diseases, and in particular heart failure and acute myocardial infarction, emphasises the need for radically new approaches, such as cell therapy, to address the underlying cause of the disease, the loss of functional myocardium. Stem cell-based therapies, whether through transplanted cells or directing innate repair, may provide regenerative approaches to cardiac diseases by halting, or even reversing, the events responsible for progression of organ failure. Cardio3 BioSciences, a leading Belgian biotechnology company focused on the discovery and development of regenerative and protective therapies for the treatment of cardiac disease, was founded in this context in 2004. The company is developing a highly innovative cell therapy approach based on a platform designed to reprogramme the patient’s own stem cells into cardiac progenitor cells. The underlying rationale behind this approach is that, in order to reconstruct cardiac tissue, stem cells need to be specific to cardiac tissue. The key is therefore to provide cardiac-specific progenitor cells to the failing heart to induce cardiac repair.

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