scholarly journals P6218Identification of Latrophilin-2, a novel receptor that specifies cardiac progenitor cells from pluripotent stem cells and is essential for heart development

2018 ◽  
Vol 39 (suppl_1) ◽  
Author(s):  
H J Cho ◽  
C S Lee ◽  
J W Lee ◽  
J W Kwon ◽  
H S Kim
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Heart Development ◽  
Cardiac Progenitor Cells

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.

Abstract 940: C-kit Positive Cardiac Progenitor Cells Contribute to the Embryonic Development of the Heart

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Grazia Iaffaldano ◽  
Yu Misao ◽  
Nicole LeCapitaine ◽  
Claudia Bearzi ◽  
Arantxa Gonzalez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Heart Development ◽  
Troponin T ◽  
Asymmetric Division ◽  
Rapid Expansion ◽  
Mouse Heart ◽  
Cardiac Progenitor Cells ◽  
Hematopoietic Stem ◽  
Simultaneous Generation

Recently, a compartment of c-kit positive cardiac progenitor cells (CPCs) has been identified in the adult mouse heart. Whether CPCs are restricted to the adult myocardium or are present throughout ontogenesis and contribute to heart development is unknown. For this purpose, a transgenic mouse in which EGFP was driven by the c-kit promoter was employed. C-kit-EGFP positive cells were present in the heart at all stages of embryonic and fetal development, and their number increased with time reaching 400 cells at E17. Symmetric and asymmetric division of c-kit-positive cells was identified respectively by the uniform and non-uniform localization of the endocytic proteins, Numb and α-adaptin. The presence of symmetric and asymmetric division was consistent with the rapid expansion of the pool of c-kit positive cells and the simultaneous generation of a committed progeny. A fraction of c-kit-EGFP positive cells expressed the myocyte transcription factors Nkx2.5 and MEF2C or specific sarcomeric proteins, α-sarcomeric actin, β-cardiac actinin, β-myosin heavy chain and troponin T. These findings demonstrated a linear relationship between CPCs and myocyte formation. Importantly, observations by two-photon microscopy showed that c-kit-EGFP positive cells in the forming heart exhibited morphogenic movements. Conversely, c-kit-EGFP positive cells from extracardiac regions or from the yolk sac did not translocate to the developing heart. Importantly, cardiac c-kit positive cells were negative for markers of hematopoietic stem cells CD34 and CD45. When c-kit-EGFP-positive cells were isolated from the embryonic heart and plated in vitro at limiting dilution, they formed single-cell derived clones. Almost all cells in the clones continued to express c-kit and EGFP. However, few cells located at the periphery of the clones were no longer positive for c-kit and EGFP and began to express sarcoplasmic proteins. In conclusion, c-kit positive cells in the developing myocardium exhibit the properties of stem cells; they are clonogenic and self-renewing and participate in the growth of the embryonic and fetal heart.

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.

scholarly journals A selective cytotoxic adenovirus vector for concentration of pluripotent stem cells in human pluripotent stem cell-derived neural progenitor cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takamasa Hirai ◽  
Ken Kono ◽  
Rumi Sawada ◽  
Takuya Kuroda ◽  
Satoshi Yasuda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Sensitive Detection ◽  
Quality And Safety

AbstractHighly sensitive detection of residual undifferentiated pluripotent stem cells is essential for the quality and safety of cell-processed therapeutic products derived from human induced pluripotent stem cells (hiPSCs). We previously reported the generation of an adenovirus (Ad) vector and adeno-associated virus vectors that possess a suicide gene, inducible Caspase 9 (iCasp9), which makes it possible to sensitively detect undifferentiated hiPSCs in cultures of hiPSC-derived cardiomyocytes. In this study, we investigated whether these vectors also allow for detection of undifferentiated hiPSCs in preparations of hiPSC-derived neural progenitor cells (hiPSC-NPCs), which have been expected to treat neurological disorders. To detect undifferentiated hiPSCs, the expression of pluripotent stem cell markers was determined by immunostaining and flow cytometry. Using immortalized NPCs as a model, the Ad vector was identified to be the most efficient among the vectors tested in detecting undifferentiated hiPSCs. Moreover, we found that the Ad vector killed most hiPSC-NPCs in an iCasp9-dependent manner, enabling flow cytometry to detect undifferentiated hiPSCs intermingled at a lower concentration (0.002%) than reported previously (0.1%). These data indicate that the Ad vector selectively eliminates hiPSC-NPCs, thus allowing for sensitive detection of hiPSCs. This cytotoxic viral vector could contribute to ensuring the quality and safety of hiPSCs-NPCs for therapeutic use.

Sign in / Sign up

Export Citation Format

Share Document