Cardiosphere derived cell

The loss of endogenous cardiac regenerative capacity within the first week of postnatal life has intensified clinical trials to induce cardiac regeneration in the adult mammalian heart using different progenitor cell types. We hypothesized that donor age-related phenotypic and functional characteristics of cardiac progenitor cells (CPC) account for mixed results of cell-based cardiac repair. We compared expression profiles and cell turnover rates of human heart-derived c-kitpos progenitors (c-kitpos CPC) and cardiosphere-derived cells (CDC) from young and adult donor origin and studied their in vitro angiogenic and cardiac differentiation potential, which can be relevant for cardiac repair...

Acute ischemic stroke is devastating to patients and their families because of few viable therapeutic options to promote recovery after reperfusion windows close. Recent breakthroughs in biotechnology have resulted in a reproducible patented process for the purification of extracellular vesicles (EVs) from human cardiosphere-derived cells (CDCs). Because CDC-EVs have many features potentially beneficial to treat acute ischemic stroke, CDC-EVs were evaluated in an established small-clot rabbit embolic stroke model, where clinically relevant end points were used to assess recovery in a more translational large animal model...

Hypertension often leads to cardiovascular disease and kidney dysfunction. Exosomes secreted from cardiosphere-derived cells (CDC-exo) and their most abundant small RNA constituent, the Y RNA fragment EV-YF1, exert therapeutic benefits after myocardial infarction. Here, we investigated the effects of CDC-exo and EV-YF1, each administered individually, in a model of cardiac hypertrophy and kidney injury induced by chronic infusion of Ang (angiotensin) II. After 2 weeks of Ang II, multiple doses of CDC-exo or EV-YF1 were administered retro-orbitally...

Cardiosphere-derived cells (CDCs) have emerged as one of the most promising stem cell types for cardiac protection and repair. Exosomes are required for the regenerative effects of human CDCs and mimic the cardioprotective benefits of CDCs such as anti-apoptotic effect in animal myocardial infarction (MI) models. Here we aimed to investigate the anti-apoptotic effect of the hypoxic and normoxic human CDCs-derived exosomes on induced apoptosis in human embryonic stem cell-derived cardiomyocytes (hESC-CMs). In this study, CDCs were cultured under normoxic (18% O2 ) and hypoxic (1% O2 ) conditions and CDC-exosomes were isolated from conditioned media by differential ultracentrifugation...

The effects of cell therapy on heart regeneration in patients with chronic cardiomyopathy have been assessed in several clinical trials. These trials can be categorized as those using noncardiac stem cells, including mesenchymal stem cells, and those using cardiac-committed cells, including KIT+ cardiac stem cells, cardiosphere-derived cells, and cardiovascular progenitor cells derived from embryonic stem cells. Although the safety of cell therapies has been consistently reported, their efficacy remains more elusive...

Background -Whether the adult mammalian heart harbors cardiac stem cells (CSCs) for regeneration of cardiomyocytes is an important yet contentious topic in the field of cardiovascular regeneration. The putative myocyte stem cell populations recognized without specific cell markers such as the cardiosphere-derived cells or with markers such as Sca1+ , Bmi1+ , Isl1+ or Abcg2+ CSCs have been reported. Moreover, it remains unclear whether putative CSCs with unknown or unidentified markers exist and give rise to de novo cardiomyocytes in the adult heart...

The object of the study was to reveal the fiber microstructural response with diffusion tensor cardiac magnetic resonance after intramyocardial exosomes secreted by cardiosphere-derived cells (CDCEXO ) in chronic porcine myocardial infarction. Porcine with myocardial infarction underwent intramyocardial delivery of human CDCEXO and placebo in a randomized placebo-controlled study. Four weeks after injection, viability improved in the CDCEXO group, whereas myocardial fiber architecture and cardiac function were preserved...

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Cell-based strategies for the treatment of ischemic diseases are at the forefront of tissue engineering and regenerative medicine. Cell therapies purportedly can play a key role in the neovascularization of ischemic tissue; however, low survival and poor cell engraftment with the host vasculature following implantation limits their potential to treat ischemic diseases. To overcome these limitations, we previously developed a growth factor sequestering hyaluronic acid (HyA)-based hydrogel that enhanced transplanted mouse cardiosphere-derived cell survival and formation of vasculature that anastomosed with host vessels...

Adult stem cells demonstrate metabolic flexibility that is regulated by cell adhesion status. The authors demonstrate that adherent cells primarily utilize glycolysis, whereas suspended cells rely on oxidative phosphorylation for their ATP needs. Akt phosphorylation transduces adhesion-mediated regulation of energy metabolism, by regulating translocation of glucose transporters (GLUT1) to the cell membrane and thus, cellular glucose uptake and glycolysis. Cell dissociation, a pre-requisite for cell transplantation, leads to energetic stress, which is mediated by Akt dephosphorylation, downregulation of glucose uptake, and glycolysis...

Genetic deficiency of dystrophin leads to disability and premature death in Duchenne muscular dystrophy (DMD), affecting the heart as well as skeletal muscle. Here, we report that clinical-stage cardiac progenitor cells, known as cardiosphere-derived cells (CDCs), improve cardiac and skeletal myopathy in the mdx mouse model of DMD. Injection of CDCs into the hearts of mdx mice augments cardiac function, ambulatory capacity, and survival. Exosomes secreted by human CDCs reproduce the benefits of CDCs in mdx mice and in human induced pluripotent stem cell-derived Duchenne cardiomyocytes...

RATIONALE: Intracoronary administration of cardiosphere-derived cells (CDCs) in patients with single ventricles resulted in a short-term improvement in cardiac function. OBJECTIVE: To test the hypothesis that CDC infusion is associated with improved cardiac function and reduced mortality in patients with heart failure. METHODS AND RESULTS: We evaluated the effectiveness of CDCs using an integrated cohort study in 101 patients with single ventricles, including 41 patients who received CDC infusion and 60 controls treated with staged palliation alone...

The heart is known for its resistance to cancer. Although different conjectures have been proposed to explain this phenomenon, none has been tested. We propose that the heart microenvironment may exert anti-cancer properties. So, our objective was to test the anti-oncogenic potential of cardiac-derived extracellular vesicles (EVs). For that EVs secreted by cardiosphere-derived cells (CDCs, heart progenitor cells) were tested in vitro on fibrosarcoma HT1080. In vivo models comprised the xenograft HT1080 fibrosarcoma in athymic mice (n=35), and spontaneous acute lymphocyte leukemia in old rats (n=44)...

Exosomes are required for the regenerative effects of human cardiosphere-derived cells (CDCs). Studies show that they mimic the cardioprotective benefits of CDCs in rodents and porcine myocardial infarction (MI) models. Hypoxic preconditioning of stem cells increases the cardioprotective effects of exosomes in MI models by enhancing angiogenesis. Several exosomal microRNAs (miRNAs) up-regulate in response to hypoxia and play a role in cardioprotective and pro-angiogenic effects. In this study, we have demonstrated that human CDCs secreted exosomes under hypoxic conditions (1% O2 for 2 days) enhanced tube formation by human umbilical vein endothelial cells (HUVECs) at a concentration of 25 µg/mL...

After a myocardial infarction, heart tissue becomes irreversibly damaged, leading to scar formation and inevitably ischemic heart failure. Of the many available interventions after a myocardial infarction, such as percutaneous intervention or pharmacological optimization, none can reverse the ischemic insult on the heart and restore cardiac function. Thus, the only available cure for patients with scarred myocardium is allogeneic heart transplantation, which comes with extensive costs, risks, and complications...

BACKGROUND: Cardiosphere derived cells (CDCs) represent a valuable source in stem cell based therapy for cardiovascular diseases, yet poor differentiation rate hinders the transplantation efficiency. The aim of this study is to check the ability of 5-Azacytidine (Aza) alone and in combination with ascorbic acid (Aza+AA) in delineating CDCs to cardiomyogenesis and the underlying Wnt signaling mechanism in induced differentiation. METHODS: CDCs were treated with Aza and Aza+AA for a period of 14 days to examine the expression of cardiac specific markers and Wnt downstream regulators by immunofluorescence, real time PCR and western blot...

Adult cardiac progenitor cells (CPCs), isolated as cardiosphere-derived cells (CDCs), represent promising candidates for cardiac regenerative therapy. CDCs can be expanded in vitro manyfolds without losing their differentiation potential, reaching numbers that are appropriate for clinical applications. Since mechanisms of successful CDC survival and engraftment in the damaged myocardium are still critical and unresolved issues, we aimed at deciphering possible key factors capable of bolstering CDC function...

Aim: The aim is to assess the effects of CDCs on heart structure, function, gene expression, and systemic parameters in aged rats. Diastolic dysfunction is characteristic of aged hearts. Cardiosphere-derived cell (CDC) therapy has exhibited several favourable effects on heart structure and function in humans and in preclinical models; however, the effects of CDCs on aging have not been evaluated. Methods and Results: We compared intra-cardiac injections of neonatal rat CDCs to vehicle (phosphate-buffered saline, PBS) in 21...

Pregestational maternal diabetes induces congenital heart defects (CHDs). Cardiac dysfunction after palliative surgical procedures contributes to the high mortality of CHD patients. Autologous or allogeneic stem cell therapies are effective for improving cardiac function in animal models and clinical trials. c-kit+ cardiac progenitor cells (CPCs), the most recognized CPCs, have the following basic properties of stem cells: self-renewal, multicellular clone formation, and differentiation into multiple cardiac lineages...

No abstract text is available yet for this article.