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Cardiosphere derived cell

Shuta Ishigami, Shinichi Ohtsuki, Takahiro Eitoku, Daiki Ousaka, Maiko Kondo, Yoshihiko Kurita, Kenta Hirai, Yosuke Fukushima, Kenji Baba, Takuya Goto, Naohiro Horio, Junko Kobayashi, Yosuke Kuroko, Yasuhiro Kotani, Sadahiko Arai, Tatsuo Iwasaki, Shuhei Sato, Shingo Kasahara, Shunji Sano, Hidemasa Oh
RATIONALE: Patients with single ventricle physiology are at high risk of mortality resulting from ventricular dysfunction. The preliminary results of the phase 1 trial showed cardiosphere-derived cells (CDCs) may be effective against congenital heart failure. OBJECTIVE: To determine if intracoronary delivery of autologous CDCs improves cardiac function in patients with single ventricle physiology. METHODS AND RESULTS: We conducted a phase 2 randomized controlled study to assign 41 patients in a 1:1 ratio who had single ventricle physiology undergoing staged-2 or -3 palliation to receive intracoronary infusion of CDCs 4 to 9 weeks after surgery or staged reconstruction alone (study A)...
January 4, 2017: Circulation Research
Tarun Chakravarty, Raj Makkar, Timothy Henry, Michelle Kittleson, John Friedman, Daniel Berman, Joao Lima, Konstantinos Malliaras, Robert Siegel, Leandro Slipczuk, Jeff Rudy, Eduardo Marban, Janice Pogoda, Linda Marban, Deborah Ascheim
No abstract text is available yet for this article.
November 1, 2016: Journal of the American College of Cardiology
Michael J Bonios, Maria Anastasiou-Nana, Despina N Perrea, Konstantinos Malliaras
BACKGROUND: Left ventricular reconstruction (LVR) has been shown to provide transient benefits in LV structure and function of infarcted hearts; however long-term results have been disappointing, as LVR-induced benefits are typically not sustained. We hypothesized that administration of cardiosphere-derived cells (CDCs), which promote myocardial repair and regeneration, may result in long-term preservation of the beneficial effects of LVR in ischemic cardiomyopathy. METHODS: Wistar Kyoto rats underwent myocardial infarction (MI) and two weeks later were randomized into 3 groups: in Group 1 (n=9) LVR was performed by plication of the infarcted apex and CDCs were injected in the infarct border zone (IBZ); group 2 animals (n=9) underwent LVR and received vehicle solution in the IBZ...
December 3, 2016: Hellenic Journal of Cardiology: HJC, Hellēnikē Kardiologikē Epitheōrēsē
Deepthi Sreerengam RajendranNair, Jayakumar Karunakaran, Renuka R Nair
Cardiosphere-derived cells (CDCs) and bone marrow mesenchymal stem cells (MSCs) are popularly used in stem cell therapy for myocardial regeneration. The cell type that survives and maintains stem cell characteristics in the adverse microenvironment following ischemia-reperfusion injury is presumed to be ideal for transplantation. The study was therefore aimed at identifying the cell type with relatively greater resistance to ischemia-reperfusion injury. CDCs were isolated from the right atrial appendage and MSCs from bone marrow of patients who underwent coronary artery bypass graft surgery...
November 14, 2016: Molecular and Cellular Biochemistry
Jennifer K Lang, Rebeccah F Young, Hashmat Ashraf, John M Canty
Numerous studies have shown a beneficial effect of cardiosphere-derived cell (CDC) therapy on regeneration of injured myocardium. Paracrine signaling by CDC secreted exosomes may contribute to improved cardiac function. However, it has not yet been demonstrated by a genetic approach that exosome release contributes to the therapeutic effect of transplanted CDCs. By employing a lentiviral knockdown (KD) strategy against neutral spingomyelinase 2 (nSMase2), a crucial gene in exosome secretion, we have defined the role of physiologically secreted human CDC-derived exosomes on cardiac fibroblast, endothelial cell and primary cardiomyocyte proliferation, cell death, migration and angiogenesis using a series of in vitro coculture assays...
2016: PloS One
Da-Qing Jiang, Tian-Xiang Gu, Zhao-Fa Xu, Shuang Liu, Xue-Yuan Li
OBJECTIVE: To investigate whether heart tissue-derived extracellular matrix (ECM) promotes the differentiation of cardiosphere-derived cells (CDCs) implanted in rat infracted myocardium to improve the cardiac structure and function. METHODS: Rat CDCs were cultured by cardiac explant methods, and ECM was prepared by decelluariztion method. In a Wistar rat model of acute myocardial infarction established by ligating the left anterior descending branch, IMDM solution, ECM suspension, 10(6) CDCs in IMDM solution, or 10(6) CDCs in ECM suspension were injected into the infracted rat myocardium (6 rats in each group)...
October 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
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 to Translational Science
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
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