scholarly journals Electrically Induced Calcium Handling in Cardiac Progenitor Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Joshua T. Maxwell ◽  
Mary B. Wagner ◽  
Michael E. Davis
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Systematic Approach ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Calcium Handling ◽  
Cardiac Progenitor Cells ◽  
Intracellular Ca ◽  
Mechanistic Basis ◽  
And Function

For nearly a century, the heart was viewed as a terminally differentiated organ until the discovery of a resident population of cardiac stem cells known as cardiac progenitor cells (CPCs). It has been shown that the regenerative capacity of CPCs can be enhanced byex vivomodification. Preconditioning CPCs could provide drastic improvements in cardiac structure and function; however, a systematic approach to determining a mechanistic basis for these modifications founded on the physiology of CPCs is lacking. We have identified a novel property of CPCs to respond to electrical stimulation by initiating intracellular Ca2+oscillations. We used confocal microscopy and intracellular calcium imaging to determine the spatiotemporal properties of the Ca2+signal and the key proteins involved in this process using pharmacological inhibition and confocal Ca2+imaging. Our results provide valuable insights into mechanisms to enhance the therapeutic potential in stem cells and further our understanding of human CPC physiology.

scholarly journals Neonatal Wnt-dependent Lgr5 positive stem cells are essential for uterine gland development

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Ryo Seishima ◽  
Carly Leung ◽  
Swathi Yada ◽  
Katzrin Bte Ahmed Murad ◽  
Liang Thing Tan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Reproductive Tract ◽  
Ex Vivo ◽  
Lineage Tracing ◽  
Major Advance ◽  
Uterine Gland ◽  
And Function ◽  
Gland Development

AbstractWnt signaling is critical for directing epithelial gland development within the uterine lining to ensure successful gestation in adults. Wnt-dependent, Lgr5-expressing stem/progenitor cells are essential for the development of glandular epithelia in the intestine and stomach, but their existence in the developing reproductive tract has not been investigated. Here, we employ Lgr5-2A-EGFP/CreERT2/DTR mouse models to identify Lgr5-expressing cells in the developing uterus and to evaluate their stem cell identity and function. Lgr5 is broadly expressed in the uterine epithelium during embryogenesis, but becomes largely restricted to the tips of developing glands after birth. In-vivo lineage tracing/ablation/organoid culture assays identify these gland-resident Lgr5high cells as Wnt-dependent stem cells responsible for uterine gland development. Adjacent Lgr5neg epithelial cells within the neonatal glands function as essential niche components to support the function of Lgr5high stem cells ex-vivo. These findings constitute a major advance in our understanding of uterine development and lay the foundations for investigating potential contributions of Lgr5+ stem/progenitor cells to uterine disorders.

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.

Abstract 18845: Induced Cardiac Progenitor Cells Differentiate Into Cardiac Lineage Cells in vivo and Improve Survival in Mice post Myocardial Infarction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Pratik A Lalit ◽  
Max R Salick ◽  
Daryl O Nelson ◽  
Jayne M Squirrell ◽  
Christina M Shafer ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Disease Modeling ◽  
Ex Vivo ◽  
Cardiac Progenitor Cells ◽  
Heart Tube ◽  
Whole Embryo Culture ◽  
Cardiac Actin ◽  
Cardiac Lineage

Several studies have reported reprogramming of fibroblasts (Fibs) to induced cardiomyocytes, and we have recently reprogrammed mouse Fibs to induced cardiac progenitor cells (iCPCs), which may be more favorable for cardiac repair because of their expandability and multipotency. Adult cardiac (AC), lung and tail-tip Fibs from an Nkx2.5-EYFP reporter mouse were reprogrammed using a combination of five defined factors into iCPCs. Transcriptome and immunocytochemistry analysis revealed that iCPCs were cardiac mesoderm-restricted progenitors that expressed CPC markers including Nkx2.5, Gata4, Irx4, Tbx5, Cxcr4, Flk1 etc. iCPCs could be extensively expanded (over 30 passages) while maintaining multipotency to differentiate in vitro into cardiac lineage cells including cardiomyocytes (CMs), smooth muscle cells and endothelial cells. iCPC derived CMs upon co-culture with mESC-derived CMs formed intercellular gap junctions, exhibited calcium transients, and contractions. The purpose of this study was to determine the in vivo potency of iCPCs. Given that the Nkx2.5-EYFP reporter identifies embryonic CPCs, we first tested the embryonic potency of iCPCs using an ex vivo whole embryo culture model injecting cells into the cardiac crescent (CC) of E8.5 mouse embryos and culturing for 24 to 48 hours. GFP labeled AC Fibs were first tested and live imaging revealed that after 24 hours these cells were rejected from the embryo proper and localized to the ecto-placental cone. In contrast, iCPCs reprogrammed from AC Fibs when injected into the CC localized to the developing heart tube and differentiated into MLC2v, αMHC and cardiac actin expressing CMs. Further we injected iCPCs into infarcted adult mouse hearts and determined their regenerative potential after 1-4 wks. The iCPCs significantly improved survival (p<0.01 Mantel-Cox test) in treated animals (75%) as compared to control (11%). Immunohistochemistry revealed that injected iCPCs localized to the scar area and differentiated into cardiac lineage cells including CMs (cardiac actin). These results indicate that lineage reprogramming of adult somatic cells into iCPCs provides a scalable cell source for cardiac regenerative therapy as well as drug discovery and disease modeling.

Stable Phenotype and Function of Immortalized Lin−Sca-1+ Cardiac Progenitor Cells in Long-Term Culture: A Step Closer to Standardization

2014 ◽  
Vol 23 (9) ◽  
pp. 1012-1026 ◽  
Author(s):  
Ana G. Freire ◽  
Diana S. Nascimento ◽  
Giancarlo Forte ◽  
Mariana Valente ◽  
Tatiana P. Resende ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Cardiac Progenitor Cells ◽  
Long Term Culture ◽  
And Function

scholarly journals After the Storm: An Objective Appraisal of the Efficacy of c-kit+ Cardiac Progenitor Cells in Preclinical Models of Heart Disease

2020 ◽  
Author(s):  
Roberto Bolli ◽  
Xian-Liang Tang ◽  
Yiru Guo ◽  
Qianhong Li
Keyword(s):  
Progenitor Cells ◽  
Ischemic Cardiomyopathy ◽  
Therapeutic Potential ◽  
Clinical Work ◽  
Good Faith ◽  
Cardiac Progenitor Cells ◽  
Review Of The Literature ◽  
Preclinical Models ◽  
Beneficial Effects ◽  
Retraction Notice

The falsification of data related to c-kit+ cardiac progenitor cells (CPCs) by a Harvard laboratory has been a veritable tragedy. Does this fraud mean that CPCs are not beneficial in models of ischemic cardiomyopathy? At least 50 studies from 26 laboratories independent of the Harvard group have reported beneficial effects of CPCs in mice, rats, pigs, and cats. The mechanism of action remains unclear. Our group has shown that CPCs do not engraft in the diseased heart, do not differentiate into new cardiac myocytes, do not regenerate dead myocardium, and thus work via paracrine mechanisms. A casualty of the misconduct at Harvard has been the SCIPIO trial, a collaboration between the Harvard group and the group in Louisville. The retraction of the SCIPIO paper was caused exclusively by issues with data generated at Harvard, not those generated in Louisville. In the retraction notice, the Lancet editors stated: “Although we do not have any reservations about the clinical work in Louisville that used the preparations from Anversa's laboratory in good faith, the lack of reliability regarding the laboratory work at Harvard means that we are now retracting this paper.” We must be careful not to dismiss all work on CPCs because of one laboratory’s misconduct. An unbiased review of the literature supports the therapeutic potential of CPCs for heart failure at the preclinical level.

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.

The Placenta as an Organ and a Source of Stem Cells and Extracellular Matrix: A Review

2016 ◽  
Vol 201 (4) ◽  
pp. 239-252 ◽  
Author(s):  
Sonja E. Lobo ◽  
Luciano César P.C. Leonel ◽  
Carla M.F.C. Miranda ◽  
Talya M. Coelho ◽  
Guilherme A.S. Ferreira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Progenitor Cells ◽  
Fetal Development ◽  
Mammalian Species ◽  
Bioactive Molecules ◽  
High Yield ◽  
Temporal Dynamic ◽  
Embryonic And Fetal Development ◽  
And Function

The placenta is a temporal, dynamic and diverse organ with important immunological features that facilitate embryonic and fetal development and survival, notwithstanding the fact that several aspects of its formation and function closely resemble tumor progression. Placentation in mammals is commonly used to characterize the evolution of species, including insights into human evolution. Although most placentas are discarded after birth, they are a high-yield source for the isolation of stem/progenitor cells and are rich in extracellular matrix (ECM), representing an important resource for regenerative medicine purposes. Interactions among cells, ECM and bioactive molecules regulate tissue and organ generation and comprise the foundation of tissue engineering. In the present article, differences among several mammalian species regarding the placental types and classifications, phenotypes and potency of placenta-derived stem/progenitor cells, placental ECM components and current placental ECM applications were reviewed to highlight their potential clinical and biomedical relevance.

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