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cardiovascular progenitor cell

Nevin Witman, Makoto Sahara
Major cardiovascular events including myocardial infarction (MI) continue to dominate morbidity rates in the developed world. Although multiple device therapies and various pharmacological agents have been shown to improve patient care and reduce mortality rates, clinicians and researchers alike still lack a true panacea to regenerate damaged cardiac tissue. Over the previous two to three decades, cardiovascular stem cell therapies have held great promise. Several stem cell-based approaches have now been shown to improve ventricular function and are documented in preclinical animal models as well as phase I and phase II clinical trials...
2018: Stem Cells International
Ivan Hernandez, Jonathan M Baio, Eric Tsay, Aida F Martinez, Tania I Fuentes, Leonard L Bailey, Nahidh W Hasaniya, Mary Kearns-Jonker
The use of cardiovascular progenitor cells (CPCs) to repair damaged myocardium has been the focus of intense research. Previous reports have shown that pretreatments, including hypoxia, improve cell function. However, the age-dependent effects of short-term hypoxia on CPCs, and the role of signaling in these effects, are unknown. Cloned neonatal and adult CPCs expressing Isl1, c-Kit, KDR, PDGFRA, and CXCR4, were preconditioned using hypoxia (1% O2 for six hours). Intracellular signaling pathway changes were modeled using Ingenuity Pathway Analysis (IPA), while qRT-PCR, flow cytometry, and immunoblotting were used to measure pathway activation...
2018: American Journal of Stem Cells
I-Chun Chen, Chin-Sung Kuo, Chih-Cheng Wu, Hsiao-Ya Tsai, Chih-Pei Lin, Szu-Yuan Li, Ruey-Hsing Chou, Po-Hsun Huang, Jaw-Wen Chen, Shing-Jong Lin
Objective: Chronic hyperuricemia is associated with cardiovascular disease, but its impact on endothelial progenitor cells (EPC) and ischemia-induced neovascularization remains unclear. Herein we investigated whether chronic hyperuricemia could impede blood flow recovery in response to tissue ischemia by suppression of EPC. Methods: Human EPC were isolated and cultured in a high-level uric acid medium for functional testing. Cell proliferation, nitric oxide (NO) production and apoptosis assay were examined...
February 6, 2018: Oncotarget
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
Hairong Chu, Hong Li, Xiumei Guan, Hong Yan, Xiaoyun Zhang, Xiaodong Cui, Xin Li, Min Cheng
Cardiovascular risk factors can negatively influence late endothelial progenitor cell (EPCs) number and functions, thus EPCs biology is a clinical implications for cardiovascular diseases. The present study aimed to investigate the potential protective effects of resveratrol (RES) on tumor necrosis factor (TNF)‑α‑induced inflammatory damage in late endothelial progenitor cells (EPCs) and to elucidate the underlying mechanisms. Late EPCs at passages 3‑5 were pretreated with RES at a concentration of 20 µmol/l for 12 h and subsequently incubated with TNF‑α (10 ng/ml) for 24 h...
February 20, 2018: Molecular Medicine Reports
Qiuling Xiang, Yan Liao, Hua Chao, Weijun Huang, Jia Liu, Haixuan Chen, Dongxi Hong, Zhengwei Zou, Andy Peng Xiang, Weiqiang Li
BACKGROUND: The LIM-homeobox transcription factor islet-1 (ISL1) has been proposed as a marker for cardiovascular progenitor cells. This study investigated whether forced expression of ISL1 in human mesenchymal stem cells (hMSCs) improves myocardial infarction (MI) treatment outcomes. METHODS: The lentiviral vector containing the human elongation factor 1α promoter, which drives the expression of ISL1 (EF1α-ISL1), was constructed using the Multisite Gateway System and used to transduce hMSCs...
February 26, 2018: Stem Cell Research & Therapy
Johan Denollet, Romy A van Felius, Paul Lodder, Paula M Mommersteeg, Inge Goovaerts, Nadine Possemiers, Luc Vanhees, Paul Beckers, Nele Pattyn, Emeline M Van Craenenbroeck
BACKGROUND: Type D personality (high negative affectivity and social inhibition) is associated with cardiovascular events and coronary plaque severity. Whether Type D is also related to functional vasomotion abnormalities is unknown. We examined concurrent and predictive associations of Type D with endothelial dysfunction in patients with coronary artery disease (CAD). METHODS: At baseline, 180 CAD patients (90% men; M = 58.0 years) completed Type D (DS14) and depression scales, and entered a 12-week exercise program...
February 20, 2018: International Journal of Cardiology
Jeong-Hyeon Kim, Kyeong-A Kim, Young-Jun Shin, Haram Kim, Arshad Majid, Ok-Nam Bae
Endothelial cells (ECs) maintain the structure and function of blood vessels and are readily exposed to exogenous and endogenous toxic substances in the circulatory system. Bone marrow-derived endothelial progenitor cells (EPCs) circulate in the blood and differentiate to EC, which are known to participate in angiogenesis and regeneration of injured vessels. Dysfunction in EPC contributes to cardiovascular complications in patients with diabetes, but the precise molecular mechanisms underlying diabetic EPC abnormalities are not completely understood...
February 23, 2018: Journal of Toxicology and Environmental Health. Part A
Maria Ida Maiorino, Giuseppe Bellastella, Ofelia Casciano, Michela Petrizzo, Maurizio Gicchino, Mariangela Caputo, Annalisa Sarnataro, Dario Giugliano, Katherine Esposito
PURPOSE: To describe gender differences concerning glycemic control, cardiovascular risk factors, diabetic complications, concomitant pathologies, and circulating endothelial progenitor cells (EPCs), in a population of young adults with type 1 diabetes. METHODS: We collected data from 300 consecutively patients (168 males and 132 females), aged 18-30 years, among those admitted at Diabetes Unit of University of Campania "Luigi Vanvitelli" (Naples, Italy) from March 2012 to January 2017...
February 17, 2018: Endocrine
Marzena Dworacka, Galina Chukanova, Saule Iskakova, Yergen Kurmambayev, Anna Wesołowska, Bartosz A Frycz, Paweł P Jagodziński, Grzegorz Dworacki
PURPOSE: Alpha-lipoic acid (ALA), widely known as an antioxidant, modifies also serum levels of angiogenic factors in type 2 diabetic patients. These pharmacological activities may influence the status of the cardiovascular system. Taking into consideration that diabetes is related to the increased cardiovascular risk we investigated several effects of ALA on angiogenic factors in the myocardium and in the aortal wall using a rat model of type 2 diabetes. METHODS: Diabetes was induced in Wistar rats by a fat-rich diet and by intraperitoneal injection of a small dose of streptozotocin (30 mg/kg)...
February 7, 2018: European Journal of Pharmaceutical Sciences
Nadia El Harane, Anaïs Kervadec, Valérie Bellamy, Laetitia Pidial, Hany J Neametalla, Marie-Cécile Perier, Bruna Lima Correa, Léa Thiébault, Nicolas Cagnard, Angéline Duché, Camille Brunaud, Mathilde Lemitre, Jeanne Gauthier, Alexandra T Bourdillon, Marc P Renault, Yeranuhi Hovhannisyan, Solenne Paiva, Alexandre R Colas, Onnik Agbulut, Albert Hagège, Jean-Sébastien Silvestre, Philippe Menasché, Nisa K E Renault
Aims: We have shown that extracellular vesicles (EVs) secreted by embryonic stem cell-derived cardiovascular progenitor cells (Pg) recapitulate the therapeutic effects of their parent cells in a mouse model of chronic heart failure (CHF). Our objectives are to investigate whether EV released by more readily available cell sources are therapeutic, whether their effectiveness is influenced by the differentiation state of the secreting cell, and through which mechanisms they act. Methods and results: The total EV secreted by human induced pluripotent stem cell-derived cardiovascular progenitors (iPSC-Pg) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) were isolated by ultracentrifugation and characterized by Nanoparticle Tracking Analysis, western blot, and cryo-electron microscopy...
February 6, 2018: European Heart Journal
Philippe Menasché, Valérie Vanneaux, Albert Hagège, Alain Bel, Bernard Cholley, Alexandre Parouchev, Isabelle Cacciapuoti, Reem Al-Daccak, Nadine Benhamouda, Hélène Blons, Onnik Agbulut, Lucie Tosca, Jean-Hugues Trouvin, Jean-Roch Fabreguettes, Valérie Bellamy, Dominique Charron, Eric Tartour, Gérard Tachdjian, Michel Desnos, Jérôme Larghero
BACKGROUND: In addition to scalability, human embryonic stem cells (hESCs) have the unique advantage of allowing their directed differentiation toward lineage-specific cells. OBJECTIVES: This study tested the feasibility of leveraging the properties of hESCs to generate clinical-grade cardiovascular progenitor cells and assessed their safety in patients with severe ischemic left ventricular dysfunction. METHODS: Six patients (median age 66...
January 30, 2018: Journal of the American College of Cardiology
Fabienne Lescroart, Xiaonan Wang, Xionghui Lin, Benjamin Swedlund, Souhir Gargouri, Adriana Sànchez-Dànes, Victoria Moignard, Christine Dubois, Catherine Paulissen, Sarah Kinston, Berthold Göttgens, Cédric Blanpain
Mouse heart development arises from Mesp1 expressing cardiovascular progenitors (CPs) that are specified during gastrulation. The molecular processes that control early regional and lineage segregation of CPs have been unclear. Here, we performed single cell RNA-sequencing of WT and Mesp1 null CPs in mice. We showed that populations of Mesp1 CPs are molecularly distinct and span the continuum between epiblast and later mesodermal cells including hematopoietic progenitors. Single cell transcriptome analysis of Mesp1-deficient CPs showed that Mesp1 is required for the exit from the pluripotent state and the induction of the cardiovascular gene expression program...
January 25, 2018: Science
Chuchun L Chang, Itsaso Garcia-Arcos, Rakel Nyrén, Gunilla Olivecrona, Ji Young Kim, Yunying Hu, Rishi R Agrawal, Andrew J Murphy, Ira J Goldberg, Richard J Deckelbaum
OBJECTIVE: Tissue macrophages induce and perpetuate proinflammatory responses, thereby promoting metabolic and cardiovascular disease. Lipoprotein lipase (LpL), the rate-limiting enzyme in blood triglyceride catabolism, is expressed by macrophages in atherosclerotic plaques. We questioned whether LpL, which is also expressed in the bone marrow (BM), affects circulating white blood cells and BM proliferation and modulates macrophage retention within the artery. APPROACH AND RESULTS: We characterized blood and tissue leukocytes and inflammatory molecules in transgenic LpL knockout mice rescued from lethal hypertriglyceridemia within 18 hours of life by muscle-specific LpL expression (MCKL0 mice)...
January 25, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Chen Fu, Baoxin Chen, Xianglan Jin, Xuemei Liu, Fengli Wang, Rongjuan Guo, Zhigang Chen, Hong Zheng, Le Wang, Yunling Zhang
Endothelial progenitor cell (EPC) dysfunction is associated with the formation of carotid atherosclerosis. It has been demonstrated that angiotensin II (Ang II) may impair the function of EPCs and puerarin, a natural product, possesses cardiovascular protective effects against oxidative stress and inflammation. Therefore, the present study aimed to investigate the beneficial effects of puerarin in Ang II‑induced EPC injury, and to elucidate the underlying mechanisms. Treatment with Ang II suppressed EPC proliferation and migration, increased the expression of the senescence marker β‑galactosidase, and the adhesion molecules intracellular adhesion molecule‑1 and vascular cell adhesion molecule‑1...
December 19, 2017: Molecular Medicine Reports
Shiyue Xu, Jun Tao, Liu Yang, Eric Zhang, Chan Boriboun, Junlan Zhou, Tianjiao Sun, Min Cheng, Kai Huang, Jiawei Shi, Nianguo Dong, Qinghua Liu, Ting C Zhao, Hongyu Qiu, Robert A Harris, Navdeep Chandel, Douglas W Losordo, Gangjian Qin
Rationale: The majority of current cardiovascular cell-therapy trials use bone marrow progenitor cells (BM PCs) and achieve only modest efficacy; the limited potential of these cells to differentiate into endothelial-lineage cells is one of the major barriers to the success of this promising therapy. We have previously reported that the E2F transcription factor 1 (E2F1) is a repressor of neovascularization following ischemic injury. Objective: We sought to define the role of E2F1 in the regulation of BM PC function...
January 22, 2018: Circulation Research
Dong Wang, LeeAnn K Li, Tiffany Dai, Aijun Wang, Song Li
Understanding the contribution of vascular cells to blood vessel remodeling is critical for the development of new therapeutic approaches to cure cardiovascular diseases (CVDs) and regenerate blood vessels. Recent findings suggest that neointimal formation and atherosclerotic lesions involve not only inflammatory cells, endothelial cells, and smooth muscle cells, but also several types of stem cells or progenitors in arterial walls and the circulation. Some of these stem cells also participate in the remodeling of vascular grafts, microvessel regeneration, and formation of fibrotic tissue around biomaterial implants...
2018: Theranostics
Keyang Zhu, Qiang Wu, Cheng Ni, Peng Zhang, Zhiwei Zhong, Yan Wu, Yingchao Wang, Yinchuan Xu, Minjian Kong, Haifeng Cheng, Zhihua Tao, Qian Yang, He Liang, Yun Jiang, Qingju Li, Jing Zhao, Jijun Huang, Fengjiang Zhang, Qi Chen, Yi Li, Jinghai Chen, Wei Zhu, Hong Yu, Jianyi Zhang, Huang-Tian Yang, Xinyang Hu, Jian'an Wang
Rationale: Human pluripotent stem cell-derived cardiovascular progenitor cells (hPSC-CVPCs) should be thoroughly investigated in large animal studies before testing in clinical trials. Objective: To clarify if hPSC-CVPCs can engraft for long time in the heart of primates after myo-cardial infarction (MI) and compare the effectiveness and safety of immunosuppression with cy-closporine alone or multiple-drug regimen (MDR) containing cyclosporine, methylprednisolone, and Simulect in cynomolgous monkeys that had received intramyocardial injections of 1×107 EGFP-expressing hPSC-CVPCs after MI...
January 17, 2018: Circulation Research
Konstantinos E Hatzistergos, Zhijie Jiang, Krystalenia Valasaki, Lauro M Takeuchi, Wayne Balkan, Preethi Atluri, Dieter Saur, Barbara Seidler, Nicholas Tsinoremas, Darcy DiFede, Joshua M Hare
Microgravity-induced alterations in the autonomic nervous system (ANS) contribute to derangements in both the mechanical and electrophysiologic function of the cardiovascular system, leading to severe symptoms in humans following space travel. Because the ANS forms embryonically from neural crest progenitors (NCs), we hypothesized that microgravity can impair NC derived cardiac structures. Accordingly, we conducted in vitro simulated microgravity experiments employing NC genetic lineage-tracing in mice with cKitCreERT2/+, Isl1nLacZ and Wnt1-Cre reporter alleles...
January 16, 2018: Stem Cells and Development
Marina Devetzi, Maria Goulielmaki, Nicolas Khoury, Demetrios A Spandidos, Georgia Sotiropoulou, Ioannis Christodoulou, Vassilis Zoumpourlis
The tissue kallikrein‑kinin system (KKS) is an endogenous multiprotein metabolic cascade which is implicated in the homeostasis of the cardiovascular, renal and central nervous system. Human tissue kallikrein (KLK1) is a serine protease, component of the KKS that has been demonstrated to exert pleiotropic beneficial effects in protection from tissue injury through its anti‑inflammatory, anti‑apoptotic, anti‑fibrotic and anti‑oxidative actions. Mesenchymal stem cells (MSCs) or endothelial progenitor cells (EPCs) constitute populations of well‑characterized, readily obtainable multipotent cells with special immunomodulatory, migratory and paracrine properties rendering them appealing potential therapeutics in experimental animal models of various diseases...
January 3, 2018: International Journal of Molecular Medicine
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