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Cardiosphere derived cell

Al Shaimaa Hasan, Lan Luo, Chen Yan, Tian-Xia Zhang, Yoshishige Urata, Shinji Goto, Safwat A Mangoura, Mahmoud H Abdel-Raheem, Shouhua Zhang, Tao-Sheng Li
Cardiosphere-derived cells (CDCs), one of the promising stem cell sources for myocardial repair, have been tested in clinical trials and resulted in beneficial effects; however, the relevant mechanisms are not fully understood. In this study, we examined the hypothesis that CDCs favor heart repair by switching the macrophages from a pro-inflammatory phenotype (M1) into a regulatory anti-inflammatory phenotype (M2). Macrophages from mice were cultured with CDCs-conditioned medium or with fibroblasts-conditioned medium as a control...
2016: PloS One
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
Romain Gallet, James Dawkins, Jackelyn Valle, Eli Simsolo, Geoffrey de Couto, Ryan Middleton, Eleni Tseliou, Daniel Luthringer, Michelle Kreke, Rachel R Smith, Linda Marbán, Bijan Ghaleh, Eduardo Marbán
AIMS: Naturally secreted nanovesicles known as exosomes are required for the regenerative effects of cardiosphere-derived cells (CDCs), and exosomes mimic the benefits of CDCs in rodents. Nevertheless, exosomes have not been studied in a translationally realistic large-animal model. We sought to optimize delivery and assess the efficacy of CDC-secreted exosomes in pig models of acute (AMI) and convalescent myocardial infarction (CMI). METHODS AND RESULTS: In AMI, pigs received human CDC exosomes (or vehicle) by intracoronary (IC) or open-chest intramyocardial (IM) delivery 30 min after reperfusion...
September 27, 2016: European Heart Journal
Tarun Chakravarty, Raj R Makkar, Deborah Ascheim, Jay H Traverse, Richard Schatz, Anthony DeMaria, Gary S Francis, Thomas J Povsic, Rachel Smith, Joao A Lima, Janice M Pogoda, Linda Marbán, Timothy D Henry
Autologous cardiosphere-derived cells (CDCs) were the first therapeutic modality to demonstrate myocardial regeneration with a decrease in scar size and an increase in viable, functional tissue. Widespread applicability of autologous CDC therapy is limited by the need for patient-specific myocardial biopsy, cell processing and quality control resulting in delays to therapy and inherent logistical and economic constraints. Pre-clinical data had demonstrated equivalent efficiency of allogeneic to autologous CDCs...
August 18, 2016: Cell Transplantation
Heidi Reich, Eleni Tseliou, Geoffrey de Couto, David Angert, Jackelyn Valle, Yuzu Kubota, Daniel Luthringer, James Mirocha, Baiming Sun, Rachel R Smith, Linda Marbán, Eduardo Marbán
BACKGROUND: A single dose of allogeneic cardiosphere-derived cells (CDCs) improves cardiac function and reduces scarring, and increases viable myocardium in the infarcted rat and pig heart without eliciting a detrimental immune response. Clinical trials using single doses of allogeneic human CDCs are underway. It is unknown whether repeat dosing confers additional benefit or if it elicits an immune response. METHODS: Wistar-Kyoto rats underwent coronary artery ligation and intramyocardial injection of CDCs, with a second thoracotomy and repeat CDC injection 3 weeks later...
May 20, 2016: Journal of Heart and Lung Transplantation
Francesco Angelini, Vittoria Ionta, Fabrizio Rossi, Fabio Miraldi, Elisa Messina, Alessandro Giacomello
INTRODUCTION: Cardiac progenitor cells (CPCs) represent a powerful tool in cardiac regenerative medicine. Pre-clinical studies suggest that most of the beneficial effects promoted by the injected cells are due to their paracrine activity exerted on endogenous cells and tissue. Exosomes are candidate mediators of this paracrine effects. According to their potential, many researchers have focused on characterizing exosomes derived from specific cell types, but, up until now, only few studies have analyzed the possible in vitro effects of bovine serum-derived exosomes on cell proliferation or differentiation...
2016: BioImpacts: BI
Jian-Yong Xu, Yee-Ki Lee, Xinru Ran, Song-Yan Liao, Jiayin Yang, Ka-Wing Au, Wing-Hon Lai, Miguel A Esteban, Hung-Fat Tse
Recent pre-clinical and clinical studies have suggested that endogenous cardiospheres (eCS) are potentially safe and effective for cardiac regeneration following myocardial infarction (MI). Nevertheless the preparation of autologous eCS requires invasive myocardial biopsy with limited yield. We describe a novel approach to generate induced cardiospheres (iCS) from adult skin fibroblasts via somatic reprogramming. After infection with Sox2, Klf4, and Oct4, iCS were generated from mouse adult skin fibroblasts treated with Gsk3β inhibitor-(2'Z,3'E)- 6-Bromoindirubin-3'-oxime and Oncostatin M...
June 22, 2016: Stem Cells
Zhenqing Li, Zhaobo Fan, Yanyi Xu, Hong Niu, Xiaoyun Xie, Zhenguo Liu, Jianjun Guan
Cardiac stem cell therapy has been considered as a promising strategy for heart tissue regeneration. Yet achieving cardiac differentiation after stem cell transplantation remains challenging. This compromises the efficacy of current stem cell therapy. Delivery of cells using matrices that stimulate the cardiac differentiation may improve the degree of cardiac differentiation in the heart tissue. In this report, we investigated whether elastic modulus of highly flexible poly(N-isopropylamide) (PNIPAAm)-based hydrogels can be modulated to stimulate the encapsulated cardiosphere derived cells (CDCs) to differentiate into cardiac lineage under static condition and dynamic stretching that mimics the heart beating condition...
June 29, 2016: ACS Applied Materials & Interfaces
Marc Hendrikx, Yanick Fanton, Leen Willems, Annick Daniels, Jeroen Declercq, Severina Windmolders, Karen Hensen, Remco Koninckx, Luc Jamaer, Jasperina Dubois, Dagmara Dilling-Boer, Jos Vandekerkhof, Filip Hendrikx, Eric Bijnens, Nick Heuts, Boris Robic, Virginie Bito, Marcel Ameloot, Paul Steels, Jean-Luc Rummens
Traditionally the heart is considered a terminally differentiated organ. However, at the beginning of this century increased mitotic activity was reported in ischemic and idiopathic dilated cardiomyopathy hearts, compared to healthy controls, underscoring the potential of regeneration after injury. Due to the presence of adult stem cells in bone marrow and their purported ability to differentiate into other cell lineages, this cell population was soon estimated to be the most suited candidate for cardiac regeneration...
2016: Current Medicinal Chemistry
Huilin Shi, Christopher A Drummond, Xiaoming Fan, Steven T Haller, Jiang Liu, Deepak Malhotra, Jiang Tian
Cardiac progenitor cells including c-kit(+) cells and cardiosphere-derived cells (CDCs) play important roles in cardiac repair and regeneration. CDCs were reported to contain only small subpopulations of c-kit(+) cells and recent publications suggested that depletion of the c-kit(+) subpopulation of cells has no effect on regenerative properties of CDCs. However, our current study showed that the vast majority of CDCs from murine heart actually express c-kit, albeit, in an intracellular and non-glycosylated form...
May 2016: Stem Cell Research
Romain Gallet, Geoffrey de Couto, Eli Simsolo, Jackelyn Valle, Baiming Sun, Weixin Liu, Eleni Tseliou, Michael R Zile, Eduardo Marbán
BACKGROUND: The pathogenesis of HFpEF is unclear, but fibrosis, inflammation and hypertrophy have been put forth as likely contributors. CDCs are heart-derived cell products with anti-fibrotic and anti-inflammatory properties. OBJECTIVES: We questioned whether allogeneic rat CDCs might be able to decrease manifestations of HFpEF in hypertensive rats. METHODS: Starting at 7 weeks of age, Dahl salt-sensitive rats were fed a high-salt diet for 6-7 weeks and randomized to receive intracoronary CDCs or placebo...
January 2016: JACC Basic Transl Sci
Nathaniel Huebsch, Peter Loskill, Nikhil Deveshwar, C Ian Spencer, Luke M Judge, Mohammad A Mandegar, Cade B Fox, Tamer M A Mohamed, Zhen Ma, Anurag Mathur, Alice M Sheehan, Annie Truong, Mike Saxton, Jennie Yoo, Deepak Srivastava, Tejal A Desai, Po-Lin So, Kevin E Healy, Bruce R Conklin
Tissue engineering approaches have the potential to increase the physiologic relevance of human iPS-derived cells, such as cardiomyocytes (iPS-CM). However, forming Engineered Heart Muscle (EHM) typically requires >1 million cells per tissue. Existing miniaturization strategies involve complex approaches not amenable to mass production, limiting the ability to use EHM for iPS-based disease modeling and drug screening. Micro-scale cardiospheres are easily produced, but do not facilitate assembly of elongated muscle or direct force measurements...
2016: Scientific Reports
Zhenqing Li, Zhaobo Fan, Yanyi Xu, Wilson Lo, Xi Wang, Hong Niu, Xiaofei Li, Xiaoyun Xie, Mahmood Khan, Jianjun Guan
Stem-cell therapy has the potential to regenerate damaged heart tissue after a heart attack. Injectable hydrogels may be used as stem-cell carriers to improve cell retention in the heart tissue. However, current hydrogels are not ideal to serve as cell carriers because most of them block blood vessels after solidification. In addition, these hydrogels have a relatively slow gelation rate (typically >60 s), which does not allow them to quickly solidify upon injection, so as to efficiently hold cells in the heart tissue...
May 4, 2016: ACS Applied Materials & Interfaces
Yong Sun, Di Chi, Miaoxin Tan, Kai Kang, Maomao Zhang, Xiangyuan Jin, Xiaoping Leng, Rui Cao, Xianglan Liu, Bo Yu, Jian Wu
OBJECTIVE: Cardiosphere-derived cells (CDCs) improve cardiac function and attenuate remodeling in ischemic and non-ischemic cardiomyopathy, and are currently obtained through myocardial biopsy. However, there is not any study on whether functional CDCs may be obtained through cadaveric autopsy with similar benefits in non-ischemic cardiomyopathy. METHODS: Cardiac tissues from human or mouse cadavers were harvested, plated at 4°C, and removed at varying time points to culture human CDCs (CLH-EDCs) and mouse CDCs (CM-CDCs)...
May 2, 2016: Cell Cycle
Tamami Nakamura, Tohru Hosoyama, Daichi Kawamura, Yuriko Takeuchi, Yuya Tanaka, Makoto Samura, Koji Ueno, Arata Nishimoto, Hiroshi Kurazumi, Ryo Suzuki, Hiroshi Ito, Kensuke Sakata, Akihito Mikamo, Tao-Sheng Li, Kimikazu Hamano
Advanced age affects various tissue-specific stem cells and decreases their regenerative ability. We therefore examined whether aging affected the quantity and quality of cardiac stem cells using cells obtained from 26 patients of various ages (from 2 to 83 years old). We collected fresh right atria and cultured cardiosphere-derived cells (CDCs), which are a type of cardiac stem cell. Then we investigated growth rate, senescence, DNA damage, and the growth factor production of CDCs. All samples yielded a sufficient number of CDCs for experiments and the cellular growth rate was not obviously associated with age...
2016: Scientific Reports
Rebeca Blázquez, Francisco Miguel Sánchez-Margallo, Verónica Crisóstomo, Claudia Báez, Juan Maestre, Verónica Álvarez, Javier G Casado
INTRODUCTION: The intrapericardial delivery has been defined as an efficient method for pharmacological agent delivery. Here we hypothesize that intrapericardial administration of cardiosphere-derived cells (CDCs) may have an immunomodulatory effect providing an optimal microenvironment for promoting cardiac repair. To our knowledge, this is the first report studying the effects of CDCs for myocardial repair using the intrapericardial delivery route. MATERIAL AND METHODS: CDCs lines were isolated, expanded and characterized by flow cytometry and PCR...
2016: PloS One
Hideaki Kanazawa, Eleni Tseliou, James F Dawkins, Geoffrey De Couto, Romain Gallet, Konstantinos Malliaras, Kristine Yee, Michelle Kreke, Ileana Valle, Rachel R Smith, Ryan C Middleton, Chak-Sum Ho, Rohan Dharmakumar, Debiao Li, Raj R Makkar, Keiichi Fukuda, Linda Marbán, Eduardo Marbán
BACKGROUND: Infusion of allogeneic cardiosphere-derived cells (allo-CDCs) postreperfusion elicits cardioprotective cellular postconditioning in pigs with acute myocardial infarction. However, the long-term effects of allo-CDCs have not been assessed. We performed a placebo-controlled pivotal study for long-term evaluation, as well as shorter-term mechanistic studies. METHODS AND RESULTS: Minipigs underwent 1.5-hour mid-left anterior descending balloon occlusion followed by reperfusion and were randomized to receive intracoronary allo-CDCs or vehicle 30 minutes postreperfusion...
February 2016: Journal of the American Heart Association
Eleni Tseliou, Hideaki Kanazawa, James Dawkins, Romain Gallet, Michelle Kreke, Rachel Smith, Ryan Middleton, Jackelyn Valle, Linda Marbán, Saibal Kar, Rajendra Makkar, Eduardo Marbán
Single-vessel, intracoronary infusion of stem cells under stop-flow conditions has proven safe but achieves only limited myocardial coverage. Continuous flow intracoronary delivery to one or more coronary vessels may achieve broader coverage for treating cardiomyopathy, but has not been investigated. Using nonocclusive coronary guiding catheters, we infused allogeneic cardiosphere-derived cells (CDCs) either in a single vessel or sequentially in all three coronary arteries in porcine ischemic cardiomyopathy and used magnetic resonance imaging (MRI) to assess structural and physiological outcomes...
2016: PloS One
Gen Suzuki
Congestive heart failure (CHF) secondary to chronic coronary artery disease is a major cause of morbidity and mortality world-wide. Its prevalence is increasing despite advances in medical and device therapies. Cell based therapies generating new cardiomyocytes and vessels have emerged as a promising treatment to reverse functional deterioration and prevent the progression to CHF. Functional efficacy of progenitor cells isolated from the bone marrow and the heart have been evaluated in preclinical large animal models...
November 26, 2015: World Journal of Cardiology
Camilla Siciliano, Isotta Chimenti, Mohsen Ibrahim, Chiara Napoletano, Giorgio Mangino, Gaia Scafetta, Giuseppe Biondi Zoccai, Erino Angelo Rendina, Antonella Calogero, Giacomo Frati, Elena De Falco
Nowadays, cardiac regenerative medicine is facing many limitations because of the complexity to find the most suitable stem cell source and to understand the regenerative mechanisms involved. Mesenchymal stem cells (MSCs) have shown great regenerative potential due to their intrinsic properties and ability to restore cardiac functionality, directly by transdifferentiation and indirectly by paracrine effects. Yet, how MSCs could respond to definite cardiac-committing microenvironments, such as that created by resident cardiac progenitor cells in the form of cardiospheres (CSs), has never been addressed...
2015: Cell Transplantation
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