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Myocardial 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
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
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
Gen Suzuki, Rebeccah F Young, Merced M Leiker, Takayuki Suzuki
A major problem in translating stem cell therapeutics is the difficulty of producing stable, long-term severe left ventricular (LV) dysfunction in a large animal model. For that purpose, extensive infarction was created in sinclair miniswine by injecting microspheres (1.5 × 10(6) microspheres, 45 μm diameter) in LAD. At 2 months after embolization, animals (n = 11) were randomized to receive allogeneic cardiosphere-derived cells derived from atrium (CDCs: 20 × 10(6), n = 5) or saline (untreated, n = 6)...
2016: Stem Cells International
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
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
Lucian Beer, Michael Mildner, Mariann Gyöngyösi, Hendrik Jan Ankersmit
For almost two decades, cell-based therapies have been tested in modern regenerative medicine to either replace or regenerate human cells, tissues, or organs and restore normal function. Secreted paracrine factors are increasingly accepted to exert beneficial biological effects that promote tissue regeneration. These factors are called the cell secretome and include a variety of proteins, lipids, microRNAs, and extracellular vesicles, such as exosomes and microparticles. The stem cell secretome has most commonly been investigated in pre-clinical settings...
October 1, 2016: Apoptosis: An International Journal on Programmed Cell Death
Murugavel Ponnusamy, Pei-Feng Li, Kun Wang
Cardiomyocyte proliferation and regeneration are key to the functional recovery of myocardial tissue from injury. In the recent years, studies on cardiomyocyte proliferation overturned the traditional belief that adult cardiomyocytes permanently withdraw from the cell cycle activity. Hence, targeting cardiomyocyte proliferation is one of the potential therapeutic strategies for myocardial regeneration and repair. To achieve this, a deep understanding of the fundamental mechanisms involved in cardiomyocyte cell cycle as well as differences between neonatal and adult cardiomyocytes' cell cycle activity is required...
September 30, 2016: Cellular and Molecular Life Sciences: CMLS
Ljubica Mandic, Denise Traxler, Alfred Gugerell, Katrin Zlabinger, Dominika Lukovic, Noemi Pavo, Georg Goliasch, Andreas Spannbauer, Johannes Winkler, Mariann Gyöngyösi
PURPOSE OF REVIEW: Myocardial infarction (MI) leading to heart failure displays an important cause of death worldwide. Adequate restoration of blood flow to prevent this transition is a crucial factor to improve long-term morbidity and mortality. Novel regenerative therapies have been thoroughly investigated within the past decades. RECENT FINDINGS: Increased angiogenesis in infarcted myocardium has shown beneficial effects on the prognosis of MI; therefore, the proangiogenic capacity of currently tested treatments is of specific interest...
2016: Current Cardiovascular Imaging Reports
Wenduo Gu, Xuechong Hong, Claire Potter, Aijuan Qu, Qingbo Xu
In recent years mesenchymal stem cells (MSCs) have emerged as a promising therapeutic cell type in regenerative medicine. They hold great promise for treating cardiovascular diseases, such as myocardial infarction and limb ischemia. MSCs may be utilized in both cell-based therapy and vascular graft engineering to restore vascular function, thereby providing therapeutic benefits to patients. The efficacy of MSCs lies in their multipotent differentiation ability towards vascular smooth muscle cells, endothelial cells and other cell types, as well as their capacity to secrete various trophic factors, which are potent in promoting angiogenesis, inhibiting apoptosis and modulating immunoreaction...
September 28, 2016: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
Anwarul Hasan, Ahmad Khattab, Mohammad Ariful Islam, Khaled Abou Hweij, Joya Zeitouny, Renae Waters, Malek Sayegh, Md Monowar Hossain, Arghya Paul
Cardiac tissue damage due to myocardial infarction (MI) is one of the leading causes of mortality worldwide. The available treatments of MI include pharmaceutical therapy, medical device implants, and organ transplants, all of which have severe limitations including high invasiveness, scarcity of donor organs, thrombosis or stenosis of devices, immune rejection, and prolonged hospitalization time. Injectable hydrogels have emerged as a promising solution for in situ cardiac tissue repair in infarcted hearts after MI...
November 2015: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Bernhard J Haubner, Thomas Schuetz, Josef M Penninger
Cardiac regeneration is one of the prime visions in cardiovascular research. The mouse neonatal apical resection and left anterior descending artery (LAD) ligation model introduced novel in vivo mammalian assays to study cardiac regeneration. However, recent reports and editorials discussed and critically questioned the value and technical reproducibility of the mouse neonatal myocardial infarction approach, making it paramount to develop and use a reproducible model system. We established a mouse neonatal myocardial infarction model by visually confirmed ligation of the LAD using microsurgery...
November 2016: Basic Research in Cardiology
Jie Ma, Yuanyuan Zhao, Li Sun, Xiaochun Sun, Xiaosu Zhao, Xiaoxian Sun, Hui Qian, Wenrong Xu, Wei Zhu
: : We have previously demonstrated the cardioprotective effects of exosomes derived from mesenchymal stem cells (MSCs). It is well-known that the activation of Akt is involved in stem cell-induced cardioprotection. In the present study, we investigated whether exosomes released from Akt-overexpressing MSCs showed a beneficial effect on cardioprotection and angiogenesis. MSCs were collected from human umbilical cord (hucMSCs), and Akt was transfected into hucMSCs (Akt-hucMSCs) by using an adenovirus transfection system...
September 22, 2016: Stem Cells Translational Medicine
Megan P O'Brien, Meagan E Carnes, Raymond L Page, Glenn R Gaudette, George D Pins
Native tissue structures possess elaborate extracellular matrix (ECM) architectures that inspire the design of fibrous structures in the field of regenerative medicine. We review the literature with respect to the successes and failures, as well as the future promise of biopolymer microthreads as scaffolds to promote endogenous and exogenous tissue regeneration. Biomimetic microthread tissue constructs have been proposed for the functional regeneration of tendon, ligament, skeletal muscle, and ventricular myocardial tissues...
June 2016: Current Stem Cell Reports
Hidetoshi Masumoto, Jun K Yamashita
Stem cell therapy is a promising therapeutic option for severe cardiac diseases that are resistant to conventional therapies. To overcome the unsatisfactory results of most clinical researches on stem cell injections to an injured heart, we are developing bioengineered cardiac tissue grafts using pluripotent stem cell-derived cardiomyocytes and vascular cells. We have validated the functional benefits of mouse embryonic stem cell-derived and human induced pluripotent stem cell-derived cardiac tissue sheets (CTSs) in a rat myocardial infarction model...
November 2016: Current Treatment Options in Cardiovascular Medicine
Akiko Tanaka, Keigo Kawaji, Amit R Patel, Takeyoshi Ota
OBJECTIVES: An extracellular matrix patch was implanted in the porcine right ventricle for in situ myocardial regeneration. A newly developed cardiovascular magnetic resonance protocol was utilized to investigate the regional physio-mechanical function of the patch. METHODS: Cardiovascular magnetic resonance was performed at 60-day after the porcine right ventricular wall full thickness substitution with an extracellular matrix cardiac patch (n = 5). Dacron patches and remote normal right ventricle served as control (n = 5/each)...
September 13, 2016: Interactive Cardiovascular and Thoracic Surgery
Jonathan Rodness, Anton Mihic, Yasuo Miyagi, Jun Wu, Richard D Weisel, Ren-Ke Li
BACKGROUND: Revascularization of the heart after myocardial infarction (MI) using growth factors delivered by hydrogel-based microspheres represents a promising therapeutic approach for cardiac regeneration. Microspheres have tuneable degradation properties and support the prolonged release of soluble factors. Cardiac patches provide mechanical restraint, preventing dilatation associated with ventricular remodelling. METHODS: We combined these approaches and produced a compacted calcium-alginate microsphere patch, restrained by a chitosan sheet, to deliver vascular endothelial growth factor (VEGF) to the heart after myocardial injury in rats...
November 2016: Acta Biomaterialia
Zahra Barabadi, Mahmoud Azami, Esmaeel Sharifi, Roya Karimi, Nasrin Lotfibakhshaiesh, Reza Roozafzoon, Mohammad Taghi Joghataei, Jafar Ai
Selecting suitable cell sources and angiogenesis induction are two important issues in myocardial tissue engineering. Human endometrial stromal cells (EnSCs) have been introduced as an abundant and easily available resource in regenerative medicine. Bioactive glass is an agent that induces angiogenesis and has been studied in some experiments. The aim of this study was to investigate in vitro differentiation capacity of endometrial stem cells into cardiomyocyte lineage and to evaluate capability of bioactive glass nanoparticles toward EnSCs differentiation into endothelial lineage and angiogenesis on hydrogel scaffold...
December 1, 2016: Materials Science & Engineering. C, Materials for Biological Applications
Yaowen Liu, Jinfu Lu, Guisen Xu, Jiaojun Wei, Zhibin Zhang, Xiaohong Li
The key to addressing the challenges facing cardiac tissue engineering is the integration of physical, chemical, and electrical cues into scaffolds. Aligned and conductive scaffolds have been fabricated as synthetic microenvironments to improve the function of cardiomyocytes. However, up to now, the influence of conductive capability and inner structure of fibrous scaffolds have not been determined on the cardiomyocyte morphologies and beating patterns. In the current study, highly aligned fibers were fabricated with loaded up to 6% of carbon nanotubes (CNTs) to modulate the electrical conductivity, while blend and coaxial electrospinning were utilized to create a bulk distribution of CNTs in fiber matrices and a spatial embedment in fiber cores, respectively...
December 1, 2016: Materials Science & Engineering. C, Materials for Biological Applications
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