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Resident myocardial stem cells

Lucio Barile, Elisabetta Cervio, Vincenzo Lionetti, Giuseppina Milano, Alessandra Ciullo, Vanessa Biemmi, Sara Bolis, Claudia Altomare, Marco Matteucci, Dario Disilvestre, Tudor Emanuel Fertig, Tiziano Torre, Stefanos Demertzis, Pierluigi Mauri, Tiziano Moccetti, Giuseppe Vassalli
Aims: Cell therapy trials using cardiac-resident progenitor cells (CPCs) and bone marrow-derived mesenchymal stem/progenitor cells (BMCs) in patients after myocardial infarction have provided encouraging results. Exosomes, nanosized extracellular vesicles of endosomal origin, figure prominently in the bioactivities of these cells. However, a head-to-head comparison of exosomes from the two cell types has not been performed yet. Methods and Results: CPCs and BMCs were derived from cardiac atrial appendage specimens and sternal bone marrow, respectively, from patients (n=20; age, 69...
March 5, 2018: Cardiovascular Research
Angelino Calderone
The intermediate filament protein nestin was identified in diverse populations of cells implicated in cardiovascular remodeling. Cardiac resident neural progenitor/stem cells constitutively express nestin and following an ischemic insult migrate to the infarct region and participate in angiogenesis and neurogenesis. A modest number of normal adult ventricular fibroblasts express nestin and the intermediate filament protein is upregulated during the progression of reparative and reactive fibrosis. Nestin depletion attenuates cell cycle re-entry suggesting that increased expression of the intermediate filament protein in ventricular fibroblasts may represent an activated phenotype accelerating the biological impact during fibrosis...
2018: Frontiers in Cell and Developmental Biology
Jin Han, Yong Sook Kim, Min-Young Lim, Han Young Kim, Saerom Kong, Mikyung Kang, Yeon Woong Choo, Ju Hee Jun, Seungmi Ryu, Hye-Yun Jeong, Jooyeon Park, Gun-Jae Jeong, Jong-Chan Lee, Gwang Hyeon Eom, Youngkeun Ahn, Byung-Soo Kim
Development of localized inflammatory environments by M1 macrophages in the cardiac infarction region exacerbates heart failure after myocardial infarction (MI). Therefore, the regulation of inflammation by M1 macrophages and their timely polarization toward regenerative M2 macrophages suggest an immunotherapy. Particularly, controlling cellular generation of reactive oxygen species (ROS), which cause M1 differentiation, and developing M2 macrophage phenotypes in macrophages propose a therapeutic approach. Previously, stem or dendritic cells were used in MI for their anti-inflammatory and cardioprotective potentials and showed inflammation modulation and M2 macrophage progression for cardiac repair...
February 7, 2018: ACS Nano
Ti Wen, Li Wang, Xue-Jun Sun, Xi Zhao, Guang-Wei Zhang, Jesse Li-Ling
Objective: To assess the effect of sevoflurane preconditioning (SFpre) on bone marrow mesenchymal stem cells (BMSCs) for the treatment of acute myocardial infarction. Results: 24 hours after the transplantation, decreased apoptosis of implanted BMSCs and up-regulation of cytokines expression were found within the ischemic area inSFpre BMSCs group compared with BMSCs group ( P < 0.05). 4 weeks later,SFpre BMSCs group showed more viable implanted BMSCs, CSC-derived cardiomyocytes, and higher vessel and myocardial density within the infarcted region and improved cardiac function, compared with control and BMSCs groups ( P < 0...
December 29, 2017: Oncotarget
Pina Marotta, Eleonora Cianflone, Iolanda Aquila, Carla Vicinanza, Mariangela Scalise, Fabiola Marino, Teresa Mancuso, Michele Torella, Ciro Indolfi, Daniele Torella
The characterization of multipotent endogenous cardiac stem cells (eCSCs) and the breakthroughs of somatic cell reprogramming to boost cardiomyocyte replacement have fostered the prospect of achieving functional heart repair/regeneration. Areas covered: Allogeneic CSC therapy through its paracrine stimulation of the endogenous resident reparative/regenerative process produces functional meaningful myocardial regeneration in pre-clinical porcine myocardial infarction models and is currently tested in the first-in-man human trial...
January 19, 2018: Expert Opinion on Biological Therapy
Chuan Li, Satoshi Matsushita, Zhengqing Li, Jianjun Guan, Atsushi Amano
Objective: Resident cardiac stem cells are expected to be a therapeutic option for patients who suffer from severe heart failure. However, uncertainty remains over whether sorting cells for c-kit, a stem cell marker, improves therapeutic outcomes. Materials and methods: Cardiac outgrowth cells cultured from explants of rat heart atrium were sorted according to their positivity (+) or negativity (-) for c-kit. These cells were exposed to hypoxia for 3 d, and subsequently harvested for mRNA expression measurement...
October 2017: Journal of Stem Cell Research & Therapy
Oualid Ayad, Christophe Magaud, Stéphane Sebille, Jocelyn Bescond, Chloé Mimbimi, Christian Cognard, Jean-Francois Faivre, Patrick Bois, Aurelien Chatelier
Recently, a new population of resident cardiac stem cells (CSCs) positive for the W8B2 marker has been identified. These CSCs are considered to be an ideal cellular source to repair myocardial damage after infarction. However, the electrophysiological profile of these cells has not been characterized yet. We first establish the conditions of isolation and expansion of W8B2+ CSCs from human heart biopsies using a magnetic sorting system followed by flow cytometry cell sorting. These cells display a spindle-shaped morphology, are highly proliferative, and possess self-renewal capacity demonstrated by their ability to form colonies...
February 2018: FEBS Journal
Arianna Mauretti, Sergio Spaans, Noortje A M Bax, Cecilia Sahlgren, Carlijn V C Bouten
The microenvironment plays a crucial role in the behavior of stem and progenitor cells. In the heart, cardiac progenitor cells (CPCs) reside in specific niches, characterized by key components that are altered in response to a myocardial infarction. To date, there is a lack of knowledge on these niches and on the CPC interplay with the niche components. Insight into these complex interactions and into the influence of microenvironmental factors on CPCs can be used to promote the regenerative potential of these cells...
2017: Stem Cells International
Etsu Suzuki, Daishi Fujita, Masao Takahashi, Shigeyoshi Oba, Hiroaki Nishimatsu
Mesenchymal stem cells (MSCs) are multipotent stem cells that reside in various organs. They have the capacity to differentiate into various cell types, including cardiomyocytes, vascular endothelial cells, and vascular smooth muscle cells. Among the various MSCs, bone marrow-derived MSCs (BMMSCs) have been widely used for treating acute myocardial infarction (AMI) and ischemic heart failure (IHF) in preclinical and clinical studies. Although the beneficial effects of BMMSCs in treating AMI and IHF were originally attributed to their capacity to differentiate into cardiac cell types, recent evidence suggests that the differentiation capacity of BMMSCs appears to be minimal and that BMMSCs exert cardioprotective effects by secreting paracrine factors...
2017: Advances in Experimental Medicine and Biology
Fiona C Lewis, Siri Deva Kumar, Georgina M Ellison-Hughes
The adult myocardium, including human, harbours a population of resident multi-potent cardiac stem cells (CSCs), which when stimulated under the right conditions can give rise to new cardiomyocytes and vasculature. Elucidation of the cellular and molecular mechanisms that govern CSC biology and their role in myocardial regeneration will allow the design and development of optimal therapeutic interventions. It is now evident that different growth factors and cytokines govern CSC survival, proliferation, migration and differentiation, as well as playing a role in activating cardiac repair mechanisms such as improving angiogenesis, cardiomyocyte survival and limiting fibrosis...
September 2, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Vanessa Bianconi, Amirhossein Sahebkar, Petri Kovanen, Francesco Bagaglia, Biagio Ricciuti, Paolo Calabrò, Giuseppe Patti, Matteo Pirro
Stem cells have the potential to differentiate into cardiovascular cell lineages and to stimulate tissue regeneration in a paracrine/autocrine manner; thus, they have been extensively studied as candidate cell sources for cardiovascular regeneration. Several preclinical and clinical studies addressing the therapeutic potential of endothelial progenitor cells (EPCs) and cardiac progenitor cells (CPCs) in cardiovascular diseases have been performed. For instance, autologous EPC transplantation and EPC mobilization through pharmacological agents contributed to vascular repair and neovascularization in different animal models of limb ischemia and myocardial infarction...
August 19, 2017: Pharmacology & Therapeutics
Carla Vicinanza, Iolanda Aquila, Mariangela Scalise, Francesca Cristiano, Fabiola Marino, Eleonora Cianflone, Teresa Mancuso, Pina Marotta, Walter Sacco, Fiona C Lewis, Liam Couch, Victoria Shone, Giulia Gritti, Annalaura Torella, Andrew J Smith, Cesare Mn Terracciano, Domenico Britti, Pierangelo Veltri, Ciro Indolfi, Bernardo Nadal-Ginard, Georgina M Ellison-Hughes, Daniele Torella
Multipotent adult resident cardiac stem cells (CSCs) were first identified by the expression of c-kit, the stem cell factor receptor. However, in the adult myocardium c-kit alone cannot distinguish CSCs from other c-kit-expressing (c-kitpos ) cells. The adult heart indeed contains a heterogeneous mixture of c-kitpos cells, mainly composed of mast and endothelial/progenitor cells. This heterogeneity of cardiac c-kitpos cells has generated confusion and controversy about the existence and role of CSCs in the adult heart...
December 2017: Cell Death and Differentiation
Elisa Yaniz-Galende, Maguelonne Roux, Sophie Nadaud, Nathalie Mougenot, Marion Bouvet, Olivier Claude, Guillaume Lebreton, Catherine Blanc, Florence Pinet, Fabrice Atassi, Claire Perret, France Dierick, Sébastien Dussaud, Pascal Leprince, David-Alexandre Trégouët, Giovanna Marazzi, David Sassoon, Jean-Sébastien Hulot
BACKGROUND: Pw1 gene expression is a marker of adult stem cells in a wide range of tissues. PW1-expressing cells are detected in the heart but are not well characterized. OBJECTIVES: The authors characterized cardiac PW1-expressing cells and their cell fate potentials in normal hearts and during cardiac remodeling following myocardial infarction (MI). METHODS: A human cardiac sample was obtained from a patient presenting with reduced left ventricular (LV) function following a recent MI...
August 8, 2017: Journal of the American College of Cardiology
Thomas J Cahill, Robin P Choudhury, Paul R Riley
Current therapies for heart failure after myocardial infarction are limited and non-curative. Although regenerative approaches are receiving significant attention, clinical efforts that involve transplantation of presumed stem and progenitor cells have largely failed to deliver. Recent studies of endogenous heart regeneration in model organisms, such as zebrafish and neonatal mice, are yielding mechanistic insights into the roles of cardiomyocyte proliferation, resident stem cell niches, neovascularization, the immune system and the extracellular matrix...
October 2017: Nature Reviews. Drug Discovery
Antonio Paolo Beltrami, Paolo Madeddu
Clinical data and basic research indicate that the structural and functional alterations that characterize the evolution of cardiac disease towards heart failure may be, at least in part, reversed. This paradigm shift is due to the accumulation of evidence indicating that, in peculiar settings, cardiomyocytes may be replenished. Moving from the consideration that cardiomyocytes are rapidly withdrawn from the cell cycle after birth, independent laboratories have tested the hypothesis that cardiac resident stem/progenitor cells resided in mammalian hearts and were important for myocardial repair...
May 31, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Deepthi Sreerengam RajendranNair, Jayakumar Karunakaran, Renuka R Nair
Cardiac stem cells reside in niches where the oxygen levels are close to 3%. For cytotherapy, cells are conventionally expanded in ambient oxygen (21% O2) which represents hyperoxia compared to the oxygen tension of niches. Cardiosphere-derived cells (CDCs) are then transplanted to host tissue with lower-O2 levels. The high-O2 gradient can reduce the efficacy of cultured cells. Based on the assumption that minimizing injury due to O2 gradients will enhance the yield of functionally efficient cells, CDCs were cultured in 3% O2 and compared with cells maintained in ambient O2...
August 2017: Molecular and Cellular Biochemistry
Guannan Li, Jianzhou Chen, Xinlin Zhang, Guixin He, Wei Tan, Han Wu, Ran Li, Yuhan Chen, Rong Gu, Jun Xie, Biao Xu
Various stem cells have been explored for the purpose of cardiac repair. However, any individual stem cell population has not been considered as the ideal source. Recently, trophoblast stem cells (TSCs), a newly described stem cell type, have demonstrated extensive plasticity. The present study evaluated the therapeutic effect of TSCs transplantation for heart regeneration in a mouse model of myocardial infarction (MI) and made a direct comparison with the most commonly used mesenchymal stem cells (MSCs). Transplantation of TSCs and MSCs led to a remarkably improved cardiac function in contrast with the PBS control, but only the TSCs exhibited the potential of differentiation into cardiomyocytes in vivo...
March 15, 2017: Scientific Reports
Gustavo Campos Ramos, Anne van den Berg, Vânia Nunes-Silva, Johannes Weirather, Laura Peters, Matthias Burkard, Mike Friedrich, Jürgen Pinnecker, Marco Abeßer, Katrin G Heinze, Kai Schuh, Niklas Beyersdorf, Thomas Kerkau, Jocelyne Demengeot, Stefan Frantz, Ulrich Hofmann
In recent years, the myocardium has been rediscovered under the lenses of immunology, and lymphocytes have been implicated in the pathogenesis of cardiomyopathies with different etiologies. Aging is an important risk factor for heart diseases, and it also has impact on the immune system. Thus, we sought to determine whether immunological activity would influence myocardial structure and function in elderly mice. Morphological, functional, and molecular analyses revealed that the age-related myocardial impairment occurs in parallel with shifts in the composition of tissue-resident leukocytes and with an accumulation of activated CD4+ Foxp3- (forkhead box P3) IFN-γ+ T cells in the heart-draining lymph nodes...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
Jordan M Greenberg, Vicente Lumbreras, Daniel Pelaez, Suhrud M Rajguru, Herman S Cheung
INTRODUCTION: Cellular cardiomyoplasty has rapidly risen to prominence in the clinic following a myocardial infarction; however, low engraftment of transplanted cells limits the therapeutic benefit to these procedures. Recently, lineage-specific stem cells differentiated into cardiomyocytes have gained much attention to assist in the repair of an injured heart tissue; however, questions regarding the ideal cell source remain. In the present study, we have identified a source that is easy to extract stem cells from and show that the cells present have a high plasticity toward the cardiomyogenic lineage...
October 2016: Tissue Engineering. Part C, Methods
Min-Young Choi, Jong-Tae Kim, Won-Jin Lee, Yunki Lee, Kyung Min Park, Young-Il Yang, Ki Dong Park
Endogenous cardiac stem cells (CSCs) are known to play a certain role in the myocardial homeostasis of the adult heart. The extracellular matrix (ECM) surrounding CSCs provides mechanical signals to regulate a variety of cell behaviors, yet the impact in the adult heart of these mechanical properties of ECM on CSC renewal and fate decisions is mostly unknown. To elucidate CSC mechanoresponses at the individual cell and myocardial level, we used the sol-to-gel transitional gelatin-poly(ethylene glycol)-tyramine (GPT) hydrogel with a tunable mechanical property to construct a three-dimensional (3D) matrix for culturing native myocardium and CSCs...
March 1, 2017: Acta Biomaterialia
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