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Carbucicchio C.,Cardiac Arrhythmia Research Center | Casella M.,Cardiac Arrhythmia Research Center | Catto V.,Cardiac Arrhythmia Research Center | Bassetti B.,Vascular Biology and Regenerative Medicine Unit | And 2 more authors.
The Canadian journal of cardiology | Year: 2015

Stem cell-based therapy is an emerging treatment for refractory ischemic cardiomyopathy. The transendocardial approach represents the most attractive method that allows direct percutaneous injections of the cell product into the ischemic territories. This clinical case shows a novel strategy designed to optimize cell endocardial delivery, based on the implementation of the 3-dimensional electroanatomical map with the intracardiac-echocardiographic reconstruction of the left ventricle, using acquired multiple slice recordings. Combined imaging was efficacious to detail the anatomical and functional characteristics of the target areas and to guide cell delivery supported by direct real-time visualization of the needle to improve procedural effectiveness and safety. Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.


Rurali E.,Vascular Biology and Regenerative Medicine Unit | Bassetti B.,Vascular Biology and Regenerative Medicine Unit | Perrucci G.L.,Vascular Biology and Regenerative Medicine Unit | Perrucci G.L.,University of Milan | And 4 more authors.
Mechanisms of Ageing and Development | Year: 2016

The bone marrow (BM) is a well-recognized source of stem/progenitor cells for cell therapy in cardiovascular diseases (CVDs). Preclinical and clinical studies suggest that endothelial progenitor cells (EPCs) contribute to reparative process of vascular endothelium and participate in angiogenesis. As for all organs and cells across the lifespan, BM and EPCs are negatively impacted by ageing due to microenvironment modifications and EPC progressive dysfunctions. The encouraging results in terms of neovascularization observed in young animals after EPC administration were mitigated in aged patients treated for ischemic CVDs. The limited efficacy of EPC-based therapy in clinical setting might be ascribed at least partly to ageing. In this review, we comprehensively discussed the age-related changes of BM and EPCs and their implication for cardiovascular cell-therapies. Finally, we examined alternative approaches under investigation to enhance EPC potency. © 2016 Elsevier Ireland Ltd.


Bassetti B.,Vascular Biology and Regenerative Medicine Unit | Capogrossi M.C.,Instituto Dermopatico dellImmacolata IRCCS | Pompilio G.,Vascular Biology and Regenerative Medicine Unit | Pompilio G.,University of Milan
Circulation Research | Year: 2016

Cardiac cell-based therapy, after a peak of untimely expectations of miraculous efficacy exceeding standard clinical practice, has faced the cardiological community and funding bodies with a predictable trough of disillusionment. In the light of more recent progresses, the field is by contrast moving toward a competitive differentiation phase, in which the resolution of the complex matching between potency of cell therapeutics and heart disease pathophysiology has the potential to make a difference for the most challenging unmet clinical needs in cardiovascular medicine. © 2016 American Heart Association, Inc.


Spaltro G.,Vascular Biology and Regenerative Medicine Unit | Avitabile D.,Vascular Biology and Regenerative Medicine Unit | De Falco E.,University of Rome La Sapienza | Gambini E.,Vascular Biology and Regenerative Medicine Unit
Frontiers in Bioscience - Landmark | Year: 2016

Stem cells are being used in the treatment of cardivovascular diseases. Here, we review the physiologic and pathologic conditions that impact the regenerative potential of stem cells in the treatment of cardiovascular diseases which include the influence of donor age and the presence of metabolic syndromes. We will also discuss strategies such as pretreatment of the recipient tissue or autologous or allogeneic stem cells by growth factors or drugs and by providing a synthetic scaffold and genetic modifications that impact the regenerative potential of stem cells. Finally, we will evaluate the current state of treatment of acute or chronic cardiovascular diseases with allogeneic stem cells.


Carbucicchio C.,Cardiac Arrhythmia Research Center | Casella M.,Cardiac Arrhythmia Research Center | Catto V.,Cardiac Arrhythmia Research Center | Bassetti B.,Vascular Biology and Regenerative Medicine Unit | And 3 more authors.
Canadian Journal of Cardiology | Year: 2015

Stem cell-based therapy is an emerging treatment for refractory ischemic cardiomyopathy. The transendocardial approach represents the most attractive method that allows direct percutaneous injections of the cell product into the ischemic territories. This clinical case shows a novel strategy designed to optimize cell endocardial delivery, based on the implementation of the 3-dimensional electroanatomical map with the intracardiac-echocardiographic reconstruction of the left ventricle, using acquired multiple slice recordings. Combined imaging was efficacious to detail the anatomical and functional characteristics of the target areas and to guide cell delivery supported by direct real-time visualization of the needle to improve procedural effectiveness and safety. © 2015 Canadian Cardiovascular Society.


PubMed | University of Genoa, Instituto Dermopatico dellImmacolata, Vascular Biology and Regenerative Medicine Unit, Medical Division and 2 more.
Type: Evaluation Studies | Journal: Cytotherapy | Year: 2015

The Pall Celeris system is a filtration-based point-of-care device designed to obtain a high concentrate of peripheral blood total nucleated cells (PB-TNCs). We have characterized the Pall Celeris-derived TNCs for their in vitro and in vivo angiogenic potency.PB-TNCs isolated from healthy donors were characterized through the use of flow cytometry and functional assays, aiming to assess migratory capacity, ability to form capillary-like structures, endothelial trans-differentiation and paracrine factor secretion. In a hind limb ischemia mouse model, we evaluated perfusion immediately and 7 days after surgery, along with capillary, arteriole and regenerative fiber density and local bio-distribution.Human PB-TNCs isolated by use of the Pall Celeris filtration system were shown to secrete a panel of angiogenic factors and migrate in response to vascular endothelial growth factor and stromal-derived factor-1 stimuli. Moreover, after injection in a mouse model of hind limb ischemia, PB-TNCs induced neovascularization by increasing capillary, arteriole and regenerative fiber numbers, with human cells detected in murine tissue up to 7 days after ischemia.The Pall Celeris system may represent a novel, effective and reliable point-of-care device to obtain a PB-derived cell product with adequate potency for therapeutic angiogenesis.


PubMed | University of Rome La Sapienza and Vascular Biology and Regenerative Medicine Unit
Type: | Journal: Frontiers in bioscience (Landmark edition) | Year: 2016

Stem cells are being used in the treatment of cardivovascular diseases. Here, we review the physiologic and pathologic conditions that impact the regenerative potential of stem cells in the treatment of cardiovascular diseases which include the influence of donor age and the presence of metabolic syndromes. We will also discuss strategies such as pretreatment of the recipient tissue or autologous or allogeneic stem cells by growth factors or drugs and by providing a synthetic scaffold and genetic modifications that impact the regenerative potential of stem cells. Finally, we will evaluate the current state of treatment of acute or chronic cardiovascular diseases with allogeneic stem cells.


PubMed | University of Lausanne, Glenfield Hospital, University of Milan, Laboratory of Molecular and Cellular Cardiology and Vascular Biology and Regenerative Medicine Unit
Type: | Journal: Journal of cellular and molecular medicine | Year: 2016

The recruitment of bone marrow (BM)-derived progenitor cells to the lung is related to pulmonary remodelling and the pathogenesis of pulmonary hypertension (PH). Although sildenafil is a known target in PH treatment, the underlying molecular mechanism is still elusive. To test the hypothesis that the therapeutic effect of sildenafil is linked to the reduced recruitment of BM-derived progenitor cells, we induced pulmonary remodelling in rats by two-week exposure to chronic hypoxia (CH, 10% oxygen), a trigger of BM-derived progenitor cells. Rats were treated with either placebo (saline) or sildenafil (1.4 mg/kg/day ip) during CH. Control rats were kept in room air (21% oxygen) with no treatment. As expected, sildenafil attenuated the CH-induced increase in right ventricular systolic pressure and right ventricular hypertrophy. However, sildenafil suppressed the CH-induced increase in c-kit


PubMed | Centro Cardiologico Monzino IRCCS, Immunology and Functional Genomics Unit, University of Pavia, Vascular Biology and Regenerative Medicine Unit and 6 more.
Type: Journal Article | Journal: European heart journal | Year: 2016

Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder mainly due to mutations in desmosomal genes, characterized by progressive fibro-adipose replacement of the myocardium, arrhythmias, and sudden death. It is still unclear which cell type is responsible for fibro-adipose substitution and which molecular mechanisms lead to this structural change. Cardiac mesenchymal stromal cells (C-MSC) are the most abundant cells in the heart, with propensity to differentiate into several cell types, including adipocytes, and their role in ACM is unknown. The aim of the present study was to investigate whether C-MSC contributed to excess adipocytes in patients with ACM.We found that, in ACM patients explanted heart sections, cells actively differentiating into adipocytes are of mesenchymal origin. Therefore, we isolated C-MSC from endomyocardial biopsies of ACM and from not affected by arrhythmogenic cardiomyopathy (NON-ACM) (control) patients. We found that both ACM and control C-MSC express desmosomal genes, with ACM C-MSC showing lower expression of plakophilin (PKP2) protein vs.Arrhythmogenic cardiomyopathy C-MSC cultured in adipogenic medium accumulated more lipid droplets than controls. Accordingly, the expression of adipogenic genes was higher in ACM vs. NON-ACM C-MSC, while expression of cell cycle and anti-adipogenic genes was lower. Both lipid accumulation and transcription reprogramming were dependent on PKP2 deficiency.Cardiac mesenchymal stromal cells contribute to the adipogenic substitution observed in ACM patients hearts. Moreover, C-MSC from ACM patients recapitulate the features of ACM adipogenesis, representing a novel, scalable, patient-specific in vitro tool for future mechanistic studies.


PubMed | University of Milan, Cardiac Arrhythmia Research Center and Vascular Biology and Regenerative Medicine Unit
Type: Case Reports | Journal: The Canadian journal of cardiology | Year: 2015

Stem cell-based therapy is an emerging treatment for refractory ischemic cardiomyopathy. The transendocardial approach represents the most attractive method that allows direct percutaneous injections of the cell product into the ischemic territories. This clinical case shows a novel strategy designed to optimize cell endocardial delivery, based on the implementation of the 3-dimensional electroanatomical map with the intracardiac-echocardiographic reconstruction of the left ventricle, using acquired multiple slice recordings. Combined imaging was efficacious to detail the anatomical and functional characteristics of the target areas and to guide cell delivery supported by direct real-time visualization of the needle to improve procedural effectiveness and safety.

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