Francesco Lodola

Francesco Lodola
Università degli Studi di Milano-Bicocca | UNIMIB · Department of Biotechnology and Biosciences

PhD

About

80
Publications
7,545
Reads
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1,773
Citations
Citations since 2017
41 Research Items
1231 Citations
2017201820192020202120222023050100150200250
2017201820192020202120222023050100150200250
2017201820192020202120222023050100150200250
2017201820192020202120222023050100150200250
Additional affiliations
December 2015 - January 2017
Istituto Italiano di Tecnologia
Position
  • PostDoc Position

Publications

Publications (80)
Article
Full-text available
Background Cardiac mesenchymal stromal cells (C-MSC) were recently shown to differentiate into adipocytes and myofibroblasts to promote the aberrant remodeling of cardiac tissue that characterizes arrhythmogenic cardiomyopathy (ACM). A calcium (Ca²⁺) signaling dysfunction, mainly demonstrated in mouse models, is recognized as a mechanism impacting...
Preprint
Non-genetic photostimulation is a novel and rapidly growing multidisciplinary field of research that aims to induce light sensitivity in living systems by exploiting exogeneous phototransducers. Here we propose a recently synthetized intramembrane photo-transducer, based on an azobenzene derivative (Ziapin2), for optical pacing of human induced plu...
Article
Phospholamban (PLN) is the natural inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2a). Heterozygous PLN-R14del mutation is associated with an arrhythmogenic dilated cardiomyopathy (DCM), whose pathogenesis has been attributed to SERCA2a “superinhibition.” The aim of the project is to test in human induced pluripotent stem cell–deriv...
Article
Therapeutic neovascularization represents a promising strategy to rescue the vascular network and restore organ function in cardiovascular disorders (CVDs), including acute myocardial infarction, heart failure, peripheral artery disease, and brain stroke. Endothelial colony forming cells (ECFCs), which are mobilized in circulation upon an ischemic...
Article
Full-text available
Phospholamban (PLN) is the natural inhibitor of the sarco/endoplasmic reticulum Ca2+ ATP-ase (SERCA2a). Heterozygous PLN p.Arg14del mutation is associated with an arrhythmogenic dilated cardiomyopathy (DCM), whose pathogenesis has been attributed to SERCA2a "superinhibition". Aim: To test in cardiomyocytes (hiPSC-CMs) derived from a PLN p.Arg14de...
Article
Endothelial colony forming cells (ECFCs) represent the most suitable cellular substrate to induce revascularization of ischemic tissues. Recently, optical excitation of the light-sensitive conjugated polymer, regioregular Poly (3-hexyl-thiophene), rr-P3HT, was found to stimulate ECFC proliferation and tube formation by activating the non-selective...
Article
Full-text available
The stem cell technology and the induced pluripotent stem cells (iPSCs) production represent an excellent alternative tool to study cardiomyopathies, which overcome the limitations associated with primary cardiomyocytes (CMs) access and manipulation. CMs from human iPSCs (hiPSC–CMs) are genetically identical to patient primary cells of origin, with...
Article
Full-text available
Many nano- and microstructured devices capable of promoting neuronal growth and network formation have been previously investigated. In certain cases, topographical cues have been successfully complemented with external bias, by employing electrically conducting scaffolds. However, the use of optical stimulation with topographical cues was rarely a...
Article
Full-text available
Cell membrane perturbation is a common way to stimulate cells by using external actuators. Recently, nanotechnology has added a number of new strategies for doing this, enlarging the scope and the range of mechanisms involved. Here, we describe a number of possible perturbation actions that are driven by light, and we try to capture the underlying...
Article
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We present a series of cationic membrane-targeted azobenzene molecules, with the aim to understand how variations in molecular architecture influence the relative optical and biological properties. 1,4-Amino-substituted azobenzene was chosen as the switching unit while the number of linked alkyl chains and their cationic end-group were systematical...
Article
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Cardiovascular diseases are the leading cause of mortality worldwide. Such a widespread diffusion makes the conditions affecting the heart and blood vessels a primary medical and economic burden. It, therefore, becomes mandatory to identify effective treatments that can alleviate this global problem. Among the different solutions brought to the att...
Article
Full-text available
Brugada syndrome (BrS) is an inherited arrhythmogenic disease that may lead to sudden cardiac death in young adults with structurally normal hearts. No pharmacological therapy is available for BrS patients. This situation highlights the urgent need to overcome current difficulties by developing novel groundbreaking curative strategies. BrS has been...
Article
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Substrate engineering for steering cell growth is a wide and well‐established area of research in the field of modern biotechnology. Here we introduce a micromachining technique to pattern an inert and transparent polymer matrix blended with a photoactive polymer. We demonstrate that the obtained scaffold combines the capability to align with that...
Preprint
Full-text available
Substrate engineering for steering cell growth is a wide and well-established area of research in the field of modern biotechnology. Here we introduce a micromachining technique to pattern an inert, transparent polymer matrix blended with a photoactive polymer. We demonstrate that the obtained scaffold combines the capability to align with that to...
Article
Full-text available
Therapeutic angiogenesis represents an emerging strategy to treat ischemic diseases by stimulating blood vessel growth to rescue local blood perfusion. Therefore, injured microvasculature may be repaired by stimulating resident endothelial cells or circulating endothelial colony forming cells (ECFCs) or by autologous cell-based therapy. Endothelial...
Article
Full-text available
The non-covalent affinity of photoresponsive molecules to biotargets represents an attractive tool for achieving effective cell photo-stimulation. Here, an amphiph-ilic azobenzene that preferentially dwells within the plasma membrane is studied. In particular, its isomerization dynamics in different media is investigated. It is found that in molecu...
Article
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Optical technologies allowing modulation of neuronal activity at high spatio-temporal resolution are becoming paramount in neuroscience. In this respect, azobenzene-based photoswitches are promising nanoscale tools for neuronal photostimulation. Here we engineered a light-sensitive azobenzene compound (Ziapin2) that stably partitions into the plasm...
Article
Full-text available
We report on the isomerization dynamics of an amphiphilic azobenzene that dwells within the plasma membrane. We found that in aggregates formed in water, the isomerization reaction is hindered, while radiative deactivation is favoured. However, once in the membrane, the molecule reacquires its isomerisation capacity. These data fully account for th...
Article
Full-text available
The control of stem and progenitor cell fate is emerging as a compelling urgency for regenerative medicine. Here, we propose a innovative strategy to gain optical control of endothelial colony-forming cell fate, which represents the only known truly endothelial precursor showing robust in vitro proliferation and overwhelming vessel formation in viv...
Article
Full-text available
Arrhythmogenic cardiomyopathy (ACM) is an inherited heart disease characterized by sudden death in young people and featured by fibro-adipose myocardium replacement, malignant arrhythmias, and heart failure. To date, no etiological therapies are available. Mutations in desmosomal genes cause abnormal mechanical coupling, trigger pro-apoptotic signa...
Article
Hybrid interfaces between living cells and nano/microstructured scaffolds have huge application potential in biotechnology, spanning from regenerative medicine and stem cell therapies to localized drug delivery and from biosensing and tissue engineering to neural computing. However, 3D architectures based on semiconducting polymers, endowed with re...
Preprint
Full-text available
Optical technologies allowing modulation of neuronal activity at high spatio-temporal resolution are becoming paramount in neuroscience. We engineered novel light-sensitive molecules by adding polar groups to a hydrophobic backbone containing azobenzene and azepane moieties. We demonstrate that the probes stably partition into the plasma membrane,...
Article
The use of light for triggering skeletal and cardiac muscles allows lower invasiveness higher selectivity and unprecedented possibility to target individual cells or even subcellular compartments in a temporally and spatially precise manner. Because cells are in general transparent, this requires the development of suitable interfaces that bestow l...
Article
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Reactive Oxygen Species (ROS) play an essential dual role in living systems. Healthy levels of ROS modulate several signaling pathways, but at the same time, when they exceed normal physiological amounts, they work in the opposite direction, playing pivotal functions in the pathophysiology of multiple severe medical conditions (i.e., cancer, diabet...
Article
Artificially enhancing light sensitivity in living cells allows control of neuronal paths or vital functions avoiding the wiring associated with the use of stimulation electrodes. Many possible strategies can be adopted for reaching this goal, including the direct photoexcitation of biological matter, the genetic modification of cells or the use of...
Article
Full-text available
Selective and rapid regulation of ionic channels is pivotal to the understanding of physiological processes and has a crucial impact in developing novel therapeutic strategies. Transient Receptor Potential (TRP) channels are emerging as essential cellular switches that allow animals to respond to their environment. In particular, the Vanilloid Rece...
Article
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Stromal derived factor-1α (SDF-1α) drives endothelial colony forming cell (ECFC) homing and incorporation within neovessels, thereby restoring tissue perfusion in ischemic tissues and favouring tumor vascularization and metastasis. SDF-1α stimulates ECFC migration by activating the Gi-protein coupled receptor, CXCR4, and then engaging the phosphoin...
Article
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Endothelial colony forming cells (ECFCs) represent a population of truly endothelial precursors that promote the angiogenic switch in solid tumors, such as breast cancer (BC). The intracellular Ca²⁺ toolkit, which drives the pro-angiogenic response to VEGF, is remodelled in tumor-associated ECFCs such that they are seemingly insensitive to this gro...
Article
Full-text available
Rationale Mutations in the cardiac Ryanodine Receptor gene ( RYR2 ) cause dominant catecholaminergic polymorphic ventricular tachycardia (CPVT), a leading cause of sudden death in apparently healthy individuals exposed to emotions or physical exercise. Objective We investigated the efficacy of allele-specific silencing by RNA interference to preve...
Article
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Catecholaminergic Polymorphic Ventricular Tachycardia type 2 (CPVT2) is a highly lethal recessive arrhythmogenic disease caused by mutations in the calsequestrin-2 (CASQ2) gene. We have previously demonstrated that viral transfer of the wild-type (WT) CASQ2 gene prevents the development of CPVT2 in a genetically induced mouse model of the disease h...
Article
Arachidonic acid (AA) stimulates endothelial cell (EC) proliferation through an increase in intracellular Ca2 + concentration ([Ca2 +]i), that, in turn, promotes nitric oxide (NO) release. AA-evoked Ca2 + signals are mainly mediated by Transient Receptor Potential Vanilloid 4 (TRPV4) channels. Circulating endothelial colony forming cells (ECFCs) re...
Article
G protein-coupled inwardly rectifying potassium (GIRK) channels play a crucial role during the migration and maturation of cerebellar granule cells (GCs) in the vermis. In the cerebellar hemispheres, however, only minor effects on the development of GCs are observed in mice with GIRK channel impairment. This regional difference may reflect distinct...
Article
Full-text available
Endothelial progenitor cells (EPCs) could be implicated in the aberrant neo-angiogenesis that features bone marrow and spleen in primary myelofibrosis (PMF) patients. However, anti-vascular endothelial growth factor (VEGF) monotherapy produce only a modest and transient effect in these individuals. We have recently shown that VEGF-induced pro-angio...
Article
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Stim1 and Orai1 are ubiquitous proteins that have long been known to mediate Ca2+ release-activated Ca2+ (CRAC) current (ICRAC) and store-operated Ca2+ entry (SOCE) only in non-excitable cells. SOCE is activated following the depletion of the endogenous Ca2+ stores, which are mainly located within the endoplasmic reticulum (ER), to replete the intr...
Article
Endothelial progenitor cells (EPCs) are mobilized into circulation to replace damaged endothelial and recapitulate the vascular network of injured tissues. Intracellular Ca(2+) signals are key to EPC activation, but it is yet to be elucidated whether they are endowed with the same blend of Ca(2+) -permeable channels expressed by mature endothelial...
Article
Background: Catecholaminergic polymorphic ventricular tachycardia is an inherited arrhythmogenic disorder characterized by sudden cardiac death in children. Drug therapy is still insufficient to provide full protection against cardiac arrest, and the use of implantable defibrillators in the pediatric population is limited by side effects. There is...
Article
Full-text available
Background: An increase in the frequency of circulating endothelial colony forming cells (ECFCs), the only subset of endothelial progenitor cells (EPCs) truly belonging to the endothelial phenotype, occurs in patients affected by primary myelofibrosis (PMF). Herein, they might contribute to the enhanced neovascularisation of fibrotic bone marrow a...
Article
Full-text available
Induced pluripotent stem cells (iPSC) offer a unique opportunity for developmental studies, disease modeling and regenerative medicine approaches in humans. The aim of our study was to create an in vitro 'patient-specific cell-based system' that could facilitate the screening of new therapeutic molecules for the treatment of catecholaminergic polym...
Article
Full-text available
Dysregulated intracellular Ca(2+) signaling is implicated in a variety of cardiac arrhythmias, including catecholaminergic polymorphic ventricular tachycardia. Spontaneous diastolic Ca(2+) release (DCR) can induce arrhythmogenic plasma membrane depolarizations, although the mechanism responsible for DCR synchronization among adjacent myocytes requi...
Article
Full-text available
Endothelial colony forming cells (ECFCs) are the only endothelial progenitor cells (EPCs) capable of acquiring a mature endothelial phenotype. ECFCs are mainly mobilized from bone-marrow to promote vascularization and represent a promising tool for cell-based therapy of severe ischemic diseases. VEGF stimulates the proliferation of peripheral blood...
Article
Rationale: The recessive form of catecholaminergic polymorphic ventricular tachycardia is caused by mutations in the cardiac calsequestrin-2 gene; this variant of catecholaminergic polymorphic ventricular tachycardia is less well characterized than the autosomal-dominant form caused by mutations in the ryanodine receptor-2 gene. Objective: We ch...
Article
Full-text available
Background: Endothelial progenitor cells (EPCs) may be recruited from bone marrow to sustain tumor vascularisation and promote the metastatic switch. Understanding the molecular mechanisms driving EPC proliferation and tubulogenesis could outline novel targets for alternative anti-angiogenic treatments. Store-operated Ca(2+) entry (SOCE), which is...
Data
Down-regulation of inositol-1,4,5-trisphosphate receptors in endothelial progenitor cells isolated from patients affected by renal cellular carcinoma. Upper panels, mRNA levels were measured by RT-PCR relative to the β-actin internal standard (see Materials and Methods) and the values obtained were reported as ΔCt. Bars represent the mean±SE of at...
Data
Evidence that CPA and ATP activate the same store-operated Ca2+ entry pathway in endothelial progenitor cells. ATP (100 µM) did not trigger any detectable elevation in [Ca2+]i upon full activation of SOCE with CPA (10 µM) in both N-EPCs (A) and RCC-EPCs (B). No Ca2+ entry occurred in either N-EPCs (C) or RCC-EPCs (D) undergoing the “Ca2+ add-back”...
Data
Genistein prevents SOCE in endothelial progenitor cells. Genistein (50 µM) fully inhibited SOCE elicited by CPA (10 µM) in both N-EPCs (A) and RCC-EPCs (B). Genistein was applied to EPCs pre-exposed to CPA under 0Ca2+ conditions 100 sec before restoration of extracellular Ca2+. Each trace is representative of 123 and 142 cells, respectively, isolat...
Data
Average of the Ca2+ signals induced by CPA and ATP in endothelial progenitor cells. Endothelial colony forming cells isolated from the peripheral blood of either healthy donors (black tracings) or patients suffering from renal cellular carcinoma (RCC) were exposed to the so-called “Ca2+ add-back” protocol. Briefly, the cells were treated with CPA (...
Data
Immunohistochemical localization of the Stim1 protein in endothelial progenitor cells. Stim1 protein was observed in both N-EPCs (A) and RCC-EPCs (B) with a labelling localized within the cytoplasm. Controls in which the primary antibody was substituted by non-immune serum show an absence of labelling (C). (TIF)