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Cardiomyocyte renewal

Amritha Yellamilli, Jop H van Berlo
The heart has a limited ability to regenerate. It is important to identify therapeutic strategies that enhance cardiac regeneration in order to replace cardiomyocytes lost during the progression of heart failure. Cardiac progenitor cells are interesting targets for new regenerative therapies because they are self-renewing, multipotent cells located in the heart. Cardiac side population cells (cSPCs), the first cardiac progenitor cells identified in the adult heart, have the ability to differentiate into cardiomyocytes, endothelial cells, smooth muscle cells, and fibroblasts...
2016: Frontiers in Cell and Developmental Biology
Thomas Eschenhagen
No abstract text is available yet for this article.
September 16, 2016: Circulation Research
Shoubao Wang, Lincai Ye, Minghui Li, Jinfen Liu, Chuan Jiang, Haifa Hong, Hongbin Zhu, Yanjun Sun
BACKGROUND: The renewal capacity of neonate human cardiomyocytes provides an opportunity to manipulate endogenous cardiogenic mechanisms for supplementing the loss of cardiomyocytes caused by myocardial infarction or other cardiac diseases. GSK-3β inhibitors have been recently shown to promote cardiomyocyte proliferation in rats and mice, thus may be ideal candidates for inducing human cardiomyocyte proliferation. METHODS: Human cardiomyocytes were isolated from right atrial specimens obtained during routine surgery for ventricle septal defect (VSD) and cultured with either GSK-3β inhibitor (CHIR-99021) or β-catenin inhibitor (IWR-1)...
August 19, 2016: Journal of Cardiovascular Pharmacology
Charles A C Williams, Rosalia Fernandez-Alonso, Jinhua Wang, Rachel Toth, Nathanael S Gray, Greg M Findlay
Embryonic stem cells (ESCs) can self-renew or differentiate into any cell type, a phenomenon known as pluripotency. Distinct pluripotent states, termed naive and primed pluripotency, have been described. However, the mechanisms that control naive-primed pluripotent transition are poorly understood. Here, we perform a targeted screen for kinase inhibitors, which modulate the naive-primed pluripotent transition. We find that XMD compounds, which selectively inhibit Erk5 kinase and BET bromodomain family proteins, drive ESCs toward primed pluripotency...
August 16, 2016: Cell Reports
Iñigo Valiente-Alandi, Carmen Albo-Castellanos, Diego Herrero, Iria Sanchez, Antonio Bernad
BACKGROUND: The inability of the adult mammalian heart to replace cells lost after severe cardiac injury compromises organ function. Although the heart is one of the least regenerative organs in the body, evidence accumulated in recent decades indicates a certain degree of renewal after injury. We have evaluated the role of cardiac Bmi1 (+) progenitor cells (Bmi1-CPC) following acute myocardial infarction (AMI). METHODS: Bmi1 (Cre/+);Rosa26 (YFP/+) (Bmi1-YFP) mice were used for lineage tracing strategy...
2016: Stem Cell Research & Therapy
S Safari, F Malekvandfard, S Babashah, A Alizadehasl, M Sadeghizadeh, M Motavaf
Coronary artery diseases (CADs) represent a significant cause of death worldwide. During recent decades the rate of cardiovascular mortality has been declined as a result of modern medicine and surgery. However, despite the fact that cardiac cells, including cardiomyocytes (CMCs), vascular smooth muscle cells (VSMC) and vascular endothelial cells (VEC), can be regenerated by cardiac adult stem cell, the regenerative capacity of these cells are limited and inadequate to functionally regenerate heart damaged tissue...
2016: Cellular and Molecular Biology
Sheetal Kashinath Medhekar, Vikas Suresh Shende, Anjali Baburao Chincholkar
Stem cells are primitive self renewing undifferentiated cell that can be differentiated into various types of specialized cells like nerve cell, skin cells, muscle cells, intestinal tissue, and blood cells. Stem cells live in bone marrow where they divide to make new blood cells and produces peripheral stem cells in circulation. Under proper environment and in presence of signaling molecules stem cells begin to develop into specialized tissues and organs. These unique characteristics make them very promising entities for regeneration of damaged tissue...
May 30, 2016: International Journal of Stem Cells
Ashley H Fong, Mónica Romero-López, Christopher M Heylman, Mark Keating, David Tran, Agua Sobrino, Anh Q Tran, Hiep H Pham, Cristhian Fimbres, Paul D Gershon, Elliot L Botvinick, Steven C George, Christopher C W Hughes
Pluripotent stem cell-derived cardiomyocytes (CMs) have great potential in the development of new therapies for cardiovascular disease. In particular, human induced pluripotent stem cells (iPSCs) may prove especially advantageous due to their pluripotency, their self-renewal potential, and their ability to create patient-specific cell lines. Unfortunately, pluripotent stem cell-derived CMs are immature, with characteristics more closely resembling fetal CMs than adult CMs, and this immaturity has limited their use in drug screening and cell-based therapies...
August 2016: Tissue Engineering. Part A
Li Nie, Shi-Jun Gao, Ya-Nan Zhao, Jacob Masika, Hong-Yan Luo, Xin-Wu Hu, Liang-Pin Zhang, Ying Zeng, Jürgen Hescheler, Hua-Min Liang
Thymosin β4 (Tβ4) is a key factor in cardiac development, growth, disease, epicardial integrity, blood vessel formation and has cardio-protective properties. However, its role in murine embryonic stem cells (mESCs) proliferation and cardiovascular differentiation remains unclear. Thus we aimed to elucidate the influence of Tβ4 on mESCs. Target genes during mESCs proliferation and differentiation were detected by real-time PCR or Western blotting, and patch clamp was applied to characterize the mESCs-derived cardiomyocytes...
June 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
Chia-I Ko, Yunxia Fan, Matthew de Gannes, Qin Wang, Ying Xia, Alvaro Puga
Lack of cell cycle checkpoints and uninterrupted passage through S-phase continuously renew the embryonic stem (ES) cell population and maintain pluripotency. Here we show that to regulate mitotic progression and pluripotency ES cells must keep the aryl hydrocarbon receptor (AHR), an environmental sensor and transcriptional regulator, in a persistent state of repression. This repression, however, is not always absolute, causing the AHR to fluctuate between reversible states of expression and repression, with a fraction of the cells escaping repression at any one time...
July 4, 2016: Stem Cells
Hidemasa Oh, Hiroshi Ito, Shunji Sano
Heart failure remains the leading cause of death worldwide, and is a burgeoning problem in public health due to the limited capacity of postnatal hearts to self-renew. The pathophysiological changes in injured hearts can sometimes be manifested as scar formation or myocardial degradation, rather than supplemental muscle regeneration to replenish lost tissue during the healing processes. Stem cell therapies have been investigated as a possible treatment approach for children and adults with potentially fatal cardiovascular disease that does not respond to current medical therapies...
June 21, 2016: Journal of Cardiology
Samuel Golpanian, Ariel Wolf, Konstantinos E Hatzistergos, Joshua M Hare
Mesenchymal stem cells (MSCs) are broadly distributed cells that retain postnatal capacity for self-renewal and multilineage differentiation. MSCs evade immune detection, secrete an array of anti-inflammatory and anti-fibrotic mediators, and very importantly activate resident precursors. These properties form the basis for the strategy of clinical application of cell-based therapeutics for inflammatory and fibrotic conditions. In cardiovascular medicine, administration of autologous or allogeneic MSCs in patients with ischemic and nonischemic cardiomyopathy holds significant promise...
July 2016: Physiological Reviews
Erhong Meng, Lalita A Shevde, Rajeev S Samant
DNAJB6 also known as mammalian relative of DnaJ (MRJ) encodes a highly conserved member of the DnaJ/Hsp40 family of co-chaperone proteins that function with Hsp70 chaperones. DNAJB6 is widely expressed in all tissues, with higher expression levels detected in the brain. DNAJB6 is involved in diverse cellular functions ranging from murine placental development, reducing the formation and toxicity of mis-folded protein aggregates, to self-renewal of neural stem cells. Involvement of DNAJB6 is implicated in multiple pathologies such as Huntington's disease, Parkinson's diseases, limb-girdle muscular dystrophy, cardiomyocyte hypertrophy and cancer...
June 2, 2016: Oncotarget
Matthew C White, Li Pang, Xi Yang
Human pluripotent stem cell-derived cardiomyocytes (PSC-CMs) are a promising human cardiac model system for drug development and toxicity screening, along with cell therapy and mechanistic research. The scalable differentiation of human PSCs into CMs provides a renewable cell source that overcomes species differences present in rodent primary CMs. In addition, induced pluripotent stem cell (iPSC) technology allows for development of patient-specific CMs, representing a valuable tool that may lead to better prediction, prevention, and treatment of cardiovascular diseases in this new era of precision medicine...
June 2, 2016: Food and Chemical Toxicology
Ge Tao, Peter C Kahr, Yuka Morikawa, Min Zhang, Mahdis Rahmani, Todd R Heallen, Lele Li, Zhao Sun, Eric N Olson, Brad A Amendt, James F Martin
Myocardial infarction results in compromised myocardial function and heart failure owing to insufficient cardiomyocyte self-renewal. Unlike many vertebrates, mammalian hearts have only a transient neonatal renewal capacity. Reactivating primitive reparative ability in the mature mammalian heart requires knowledge of the mechanisms that promote early heart repair. By testing an established Hippo-deficient heart regeneration mouse model for factors that promote renewal, here we show that the expression of Pitx2 is induced in injured, Hippo-deficient ventricles...
May 25, 2016: Nature
Charly Jehanno, Gilles Flouriot, Floriane Nicol-Benoît, Yann Le Page, Pascale Le Goff, Denis Michel
Cancer is generally conceived as a dedifferentiation process in which quiescent post-mitotic differentiated cells acquire stem-like properties and the capacity to proliferate. This view holds for the initial stages of carcinogenesis but is more questionable for advanced stages when the cells can transdifferentiate into the contractile phenotype associated to migration and metastasis. Singularly from this perspective, the hallmark of the most aggressive cancers would correspond to a genuine differentiation status, even if it is different from the original one...
February 17, 2016: Breast Disease
Junjie Xiao, Ping Chen, Yi Qu, Pujiao Yu, Jianhua Yao, Hongbao Wang, Siyi Fu, Yihua Bei, Yan Chen, Lin Che, Jiahong Xu
Exercise can induce physiological cardiac growth, which is featured by enlarged cardiomyocyte cell size and formation of new cardiomyocytes. Telocytes (TCs) are a recently identified distinct interstitial cell type, existing in many tissues and organs including heart. TCs have been shown to form a tandem with cardiac stem/progenitor cells in cardiac stem cell niches, participating in cardiac regeneration and repair. Although exercise-induced cardiac growth has been confirmed as an important way to promote cardiac regeneration and repair, the response of cardiac TCs to exercise is still unclear...
May 2016: Journal of Cellular and Molecular Medicine
Ping Zhou, Fujian Wu, Tiancheng Zhou, Xiujuan Cai, Siqi Zhang, Xiaohong Zhang, Qiuhong Li, Yongliang Li, Yunfei Zheng, Mengke Wang, Feng Lan, Guangjin Pan, Duanqing Pei, Shicheng Wei
Human pluripotent stem cells (hPSCs) possess great value in the aspect of cellular therapies due to its self-renewal and potential to differentiate into all somatic cell types. A few defined synthetic surfaces such as polymers and adhesive biological materials conjugated substrata were established for the self-renewal of hPSCs. However, none of them was effective in the generation of human induced pluripotent stem cells (hiPSCs) and long-term maintenance of multiple hPSCs, and most of them required complicated manufacturing processes...
May 2016: Biomaterials
Guang-yan Yu, Tong Cao, Xiao-hui Zou, Xue-hui Zhang, Xin Fu, Shuang-qing Peng, Xu-liang Deng, Sheng-lin Li, He Liu, Ran Xiao, Hong-wei Ouyang, Hui Peng, Xiao Chen, Zeng-ming Zhao, Xiao-ying Wang, Hai-qin Fang, Lu Lu, Yu-lan Ren, Ming-ming Xu
The human embryonic stem cells (hESCs) serve as a self-renewable, genetically-healthy, pluripotent and single source of all body cells, tissues and organs. Therefore, it is considered as the good standard for all human stem cells by US, Europe and international authorities. In this study, the standard and healthy human mesenchymal progenitors, ligament tissues, cardiomyocytes, keratinocytes, primary neurons, fibroblasts, and salivary serous cells were differentiated from hESCs. The human cellular health-safety of NaF, retinoic acid, 5-fluorouracil, dexamethasone, penicillin G, adriamycin, lead acetate PbAc, bisphenol A-biglycidyl methacrylate (Bis-GMA) were evaluated selectively on the standardized platforms of hESCs, hESCs-derived cardiomyocytes, keratinocytes, primary neurons, and fibroblasts...
February 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
Adriana Adameova, Eva Goncalvesova, Adrian Szobi, Naranjan S Dhalla
As cardiomyocytes have a limited capability for proliferation, renewal, and repair, the loss of heart cells followed by replacement with fibrous tissue is considered to result in the development of ventricular dysfunction and progression to heart failure (HF). The loss of cardiac myocytes in HF has been traditionally believed to occur mainly due to programmed apoptosis or unregulated necrosis. While extensive research work is being carried out to define the exact significance and contribution of both these cell death modalities in the development of HF, recent knowledge has indicated the existence and importance of a different form of cell death called necroptosis in the failing heart...
March 2016: Heart Failure Reviews
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