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Cardiac regeneration

Megumi Mathison, Vivek P Singh, Maria J Chiuchiolo, Deepthi Sanagasetti, Yun Mao, Vivekkumar B Patel, Jianchang Yang, Stephen M Kaminsky, Ronald G Crystal, Todd K Rosengart
OBJECTIVE: The reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells improves ventricular function in myocardial infarction models. Only integrating persistent expression vectors have thus far been used to induce reprogramming, potentially limiting its clinical applicability. We therefore tested the reprogramming potential of nonintegrating, acute expression adenoviral (Ad) vectors. METHODS: Ad or lentivirus vectors encoding Gata4 (G), Mef2c (M), and Tbx5 (T) were validated in vitro...
September 23, 2016: Journal of Thoracic and Cardiovascular Surgery
Jinah Jang, Hun-Jun Park, Seok-Won Kim, Heejin Kim, Ju Young Park, Soo Jin Na, Hyeon Ji Kim, Moon Nyeo Park, Seung Hyun Choi, Sun Hwa Park, Sung Won Kim, Sang-Mo Kwon, Pum-Joon Kim, Dong-Woo Cho
Stem cell therapy is a promising therapeutic method for the treatment of ischemic heart diseases; however, some challenges prohibit the efficacy after cell delivery due to hostile microenvironment of the injured myocardium. 3D printed pre-vascularized stem cell patch can enhance the therapeutic efficacy for cardiac repair through promotion of rapid vascularization after patch transplantation. In this study, stem cell-laden decellularized extracellular matrix bioinks are used in 3D printing of pre-vascularized and functional multi-material structures...
October 14, 2016: Biomaterials
Hongyu Sun, Jiajia Tang, Yongchao Mou, Jing Zhou, Linlin Qu, Kayla Duval, Zhu Huang, Ning Lin, Ruiwu Dai, Chengxiao Liang, Zi Chen, Lijun Tang, Fuzhou Tian
: Carbon nanotube (CNT)-based hydrogels have been shown to support cardiomyocyte growth and function. However, their role in cellular integrity among cardiomyocytes has not been studied in detail and the mechanisms underlying this process remain unclear. Here, single walled CNTs incorporated into gelatin with methacrylate anhydride (CNT/GelMA) hydrogels were utilized to construct cardiac tissues, which enhanced cardiomyocyte adhesion and maturation. Furthermore, through the use of immunohistochemical staining, transmission electron microscopy and intracellular calcium transient measurement, the incorporation of CNTs into the scaffolds was observed to markedly enhance the assembly and formation in the cardiac constructs...
October 18, 2016: Acta Biomaterialia
Martino Deidda, Rosalinda Madonna, Ruggiero Mango, Pasquale Pagliaro, Pier P Bassareo, Lucia Cugusi, Silvio Romano, Maria Penco, Francesco Romeo, Giuseppe Mercuro
Despite advances in supportive and protective therapy for myocardial function, heart failure caused by various clinical conditions, including cardiomyopathy due to antineoplastic therapy, remains a major cause of morbidity and mortality. Because of the limitations associated with current therapies, investigators have been searching for alternative treatments that can effectively repair the damaged heart and permanently restore its function. Damage to the heart can result from both traditional chemotherapeutic agents, such as anthracyclines, and new targeted therapies, such as trastuzumab...
May 2016: Journal of Cardiovascular Medicine
Liu Liu, Ienglam Lei, Zhong Wang
PURPOSE OF REVIEW: Cardiovascular disease is the leading cause of death in the world today, and the death rate has remained virtually unchanged in the last 20 years (American Heart Association). This severe life-threatening disease underscores a critical need for developing novel therapeutic strategies to effectively treat this devastating disease. Cell-based therapy represents an extremely promising approach. Generation of induced cardiomyocytes (iCMs) directly from fibroblasts offers an attractive novel strategy for in-situ heart regeneration...
October 15, 2016: Current Opinion in Organ Transplantation
David Legouis, Pierre Galichon, Aurélien Bataille, Sylvie Chevret, Sophie Provenchère, Anne Boutten, Dimitrios Buklas, Jean-Luc Fellahi, Jean-Luc Hanouz, Alexandre Hertig
BACKGROUND: There is recent evidence to show that patients suffering from acute kidney injury are at increased risk of developing chronic kidney disease despite the fact that surviving tubular epithelial cells have the capacity to fully regenerate renal tubules and restore renal function within days or weeks. The aim of the study was to investigate the impact of acute kidney injury on de novo chronic kidney disease. METHODS: The authors conducted a retrospective population-based cohort study of patients initially free from chronic kidney disease who were scheduled for elective cardiac surgery with cardiopulmonary bypass and who developed an episode of acute kidney injury from which they recovered...
October 17, 2016: Anesthesiology
Nikola Dobrilovic, Peter Soukas, Immad Sadiq, Lisa Goldstein, Jaishankar Raman
BACKGROUND: The CorMatrix (CorMatrix Cardiovascular, Roswell, Ga) biologic extracellular patch derived from porcine small intestinal mucosa provides a biologic scaffold for cellular ingrowth and eventual tissue regeneration. It has been used in a variety of applications, including cardiac and vascular repair procedures. METHODS: CorMatrix was used as a patch arterioplasty for femoral artery repair in conjunction with endarterectomy for seven separate procedures in six patients (one patient underwent staged, bilateral femoral procedures)...
October 14, 2016: Journal of Vascular Surgery
Kai Zhu, Dingqian Liu, Hao Lai, Jun Li, Chunsheng Wang
MicroRNAs (miRNAs) families have been found to be powerful regulators in a wide variety of diseases, which enables the possible use of miRNAs in therapeutic strategies for cardiac repair after ischemic heart disease. This review provides some general insights into miRNAs modulation for development of current molecular and cellular therapeutics in cardiac repair, including endogenous regeneration, endogenous repair, stem cells transplantation, and reprogramming. We also review the delivery strategies for miRNAs modulation, and briefly summarize the current bench and clinical efforts that are being made to explore miRNAs as the future therapeutic target...
September 2016: Journal of Thoracic Disease
Hector A Cabrera-Fuentes, Julian Aragones, Jürgen Bernhagen, Andreas Boening, William A Boisvert, Hans E Bøtker, Heerajnarain Bulluck, Stuart Cook, Fabio Di Lisa, Felix B Engel, Bernd Engelmann, Fulvia Ferrazzi, Péter Ferdinandy, Alan Fong, Ingrid Fleming, Erich Gnaiger, Sauri Hernández-Reséndiz, Siavash Beikoghli Kalkhoran, Moo Hyun Kim, Sandrine Lecour, Elisa A Liehn, Michael S Marber, Manuel Mayr, Tetsuji Miura, Sang-Bing Ong, Karlheinz Peter, Daniel Sedding, Manvendra K Singh, M Saadeh Suleiman, Hans J Schnittler, Rainer Schulz, Winston Shim, Daniel Tello, Carl-Wilhelm Vogel, Malcolm Walker, Qilong Oscar Yang Li, Derek M Yellon, Derek J Hausenloy, Klaus T Preissner
In this meeting report, particularly addressing the topic of protection of the cardiovascular system from ischemia/reperfusion injury, highlights are presented that relate to conditioning strategies of the heart with respect to molecular mechanisms and outcome in patients' cohorts, the influence of co-morbidities and medications, as well as the contribution of innate immune reactions in cardioprotection. Moreover, developmental or systems biology approaches bear great potential in systematically uncovering unexpected components involved in ischemia-reperfusion injury or heart regeneration...
November 2016: Basic Research in Cardiology
Chiara Cencioni, Sandra Atlante, Matteo Savoia, Fabio Martelli, Antonella Farsetti, Maurizio C Capogrossi, Andreas M Zeiher, Carlo Gaetano, Francesco Spallotta
Organ-specific mesenchymal cells naturally reside in the stroma, where they are exposed to some environmental variables affecting their biology and functions. Risk factors such as diabetes or aging influence their adaptive response. In these cases, permanent epigenetic modifications may be introduced in the cells with important consequences on their local homeostatic activity and therapeutic potential. Numerous results suggest that mesenchymal cells, virtually present in every organ, may contribute to tissue regeneration mostly by paracrine mechanisms...
October 11, 2016: Pharmacology & Therapeutics
Kristin Wenzel, Rasmita Samal, Elke Hammer, Vishnu M Dhople, Stefan Gross, Uwe Völker, Stephan B Felix, Stephanie Könemann
Cardiac progenitor cells (CPCs) trigger regenerative processes via paracrine mechanisms in response to changes in their environment. In the present study we explored alterations in the secretory activity of CPCs induced by raised aldosterone levels symptomatic for heart failure. The cytokine profile of the supernatant of CPCs that were treated with the mineralocorticoid showed an induction of interleukin-6 secretion. Mass spectrometric analyses revealed an increase in the abundance of secreted proteins associated with regeneration and cell migration like gelsolin and galectin-1...
October 11, 2016: Molecular and Cellular Endocrinology
J Patrick Gonzalez, Sergii Kyrychenko, Victoria Kyrychenko, Joel S Schneider, Celine J Granier, Eric Himelman, Kevin Lahey, Qingshi Zhao, Ghassan Yehia, Yuan-Xiang Tao, Mantu Bhaumik, Natalia Shirokova, Diego Fraidenraich
Duchenne muscular dystrophy (DMD) is characterized by the loss of the protein dystrophin, leading to muscle fragility, progressive weakening, and susceptibility to mechanical stress. Although dystrophin-negative mdx mouse models have classically been used to study DMD, phenotypes appear mild compared to patients. As a result, characterization of muscle pathology, especially in the heart, has proven difficult. We report that injection of mdx embryonic stem cells (ESCs) into Wild Type (WT) blastocysts produces adult mouse chimeras with severe DMD phenotypes in the heart and skeletal muscle...
October 13, 2016: Stem Cells
Bin Yang, Ping Yan, Hui Gong, Lin Zuo, Ying Shi, Jian Guo, Rui Guo, Jun Xie, Bao Li
Myocyte apoptosis is a key determinant of cardiac recovery and prognosis of patients with acute myocardial infarction (AMI). Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), a member of TNF superfamily, is a pro-inflammatory and pro-angiogenic cytokine implicated in physiological tissue regeneration and wound repair and is closely related to cardiac remodeling, dysfunction and fibrosis. However, the role of TWEAK and its receptor Fn14 in the cardiomyocyte apoptosis is still poorly understood...
2016: American Journal of Translational Research
Yuji Shiba, Toshihito Gomibuchi, Tatsuichiro Seto, Yuko Wada, Hajime Ichimura, Yuki Tanaka, Tatsuki Ogasawara, Kenji Okada, Naoko Shiba, Kengo Sakamoto, Daisuke Ido, Takashi Shiina, Masamichi Ohkura, Junichi Nakai, Narumi Uno, Yasuhiro Kazuki, Mitsuo Oshimura, Itsunari Minami, Uichi Ikeda
Induced pluripotent stem cells (iPSCs) constitute a potential source of autologous patient-specific cardiomyocytes for cardiac repair, providing a major benefit over other sources of cells in terms of immune rejection. However, autologous transplantation has substantial challenges related to manufacturing and regulation. Although major histocompatibility complex (MHC)-matched allogeneic transplantation is a promising alternative strategy, few immunological studies have been carried out with iPSCs. Here we describe an allogeneic transplantation model established using the cynomolgus monkey (Macaca fascicularis), the MHC structure of which is identical to that of humans...
October 10, 2016: Nature
Arianna Mauretti, Noortje A M Bax, Mieke H van Marion, Marie José Goumans, Cecilia Sahlgren, Carlijn V C Bouten
For emerging cardiac regeneration strategies, it is essential to know if and how cardiac stem cells sense and respond to the mechanical stimuli provided by their environment in the beating heart. Here, we study the response to cyclic strain of undifferentiated and predifferentiated human cardiomyocyte progenitor cells (CMPCs), as well as the formation and activation of the cellular structures involved in mechanosensing, that we termed 'mechanosome'. Once verified that the applied uniaxial cyclic strain (10%, 0...
September 12, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
Elena Cambria, Julia Steiger, Julia Günter, Annina Bopp, Petra Wolint, Simon P Hoerstrup, Maximilian Y Emmert
Cardiac stem cell therapy holds great potential to prompt myocardial regeneration in patients with ischemic heart disease. The selection of the most suitable cell type is pivotal for its successful application. Various cell types, including crude bone marrow mononuclear cells, skeletal myoblast, and hematopoietic and endothelial progenitors, have already advanced into the clinical arena based on promising results from different experimental and preclinical studies. However, most of these so-called first-generation cell types have failed to fully emulate the promising preclinical data in clinical trials, resulting in heterogeneous outcomes and a critical lack of translation...
July 2016: Transfusion Medicine and Hemotherapy
Zhiqiang Lin, Haidong Guo, Yuan Cao, Sylvia Zohrabian, Pingzhu Zhou, Qing Ma, Nathan VanDusen, Yuxuan Guo, Jin Zhang, Sean M Stevens, Feng Liang, Qimin Quan, Pim R van Gorp, Amy Li, Cristobal Dos Remedios, Aibin He, Vassilios J Bezzerides, William T Pu
Binding of the transcriptional co-activator YAP with the transcription factor TEAD stimulates growth of the heart and other organs. YAP overexpression potently stimulates fetal cardiomyocyte (CM) proliferation, but YAP's mitogenic potency declines postnatally. While investigating factors that limit YAP's postnatal mitogenic activity, we found that the CM-enriched TEAD1 binding protein VGLL4 inhibits CM proliferation by inhibiting TEAD1-YAP interaction and by targeting TEAD1 for degradation. Importantly, VGLL4 acetylation at lysine 225 negatively regulated its binding to TEAD1...
October 4, 2016: Developmental Cell
Parvin Abraham, Tessy Thomas Maliekal
Research of the past two decades has proved the relevance of single cell biology in basic research and translational medicine. Successful detection and isolation of specific subsets is the key to understand their functional heterogeneity. Antibodies are conventionally used for this purpose, but their relevance in certain contexts is limited. In this review, we discuss some of these contexts, posing bottle neck for different fields of biology including biomedical research. With the advancement of chemistry, several methods have been introduced to overcome these problems...
October 6, 2016: Cellular and Molecular Life Sciences: CMLS
M Tavafoghi, M Cerruti
Polar and charged amino acids (AAs) are heavily expressed in non-collagenous proteins (NCPs), and are involved in hydroxyapatite (HA) mineralization in bone. Here, we review what is known on the effect of single AAs on HA precipitation. Negatively charged AAs, such as aspartic acid, glutamic acid (Glu) and phosphoserine are largely expressed in NCPs and play a critical role in controlling HA nucleation and growth. Positively charged ones such as arginine (Arg) or lysine (Lys) are heavily involved in HA nucleation within extracellular matrix proteins such as collagen...
October 2016: Journal of the Royal Society, Interface
Gordana Vunjak-Novakovic
Tissue-engineered regeneration of a failing human heart remains a major challenge, while cardiovascular disease continues to take more lives than all cancers combined. Much has been learned from the basic and clinical studies, with the most interesting developments happening at the interfaces of disciplines. This seems to be the right time to step back and rethink the evolving paradigm of tissue engineering, and to reflect about the most promising directions to take. We clearly need new therapeutic modalities that are effective and yet simple enough to be practical, and the field is looking into the therapeutic potential of stem-progenitor cells, cardiac and vascular, that are enabled by bioactive factors and functionalized biomaterials...
September 6, 2016: Journal of Thoracic and Cardiovascular Surgery
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