Biology subjects

Biagi, D.

Publications and source records attributed to Biagi, D..

4 recordsLinked to original sources

bioRxiv2024

Graphene-polymer Nanofibers Enable Optically Induced Electrical Maturation in Stem Cell-Derived Cardiomyocytes and Brain Organoids

Human pluripotent stem cell (hPSC)-derived electrically excitable cells provide a unique window into development, but they remain electrically immature partially due to the lack of chronic stimulation. Here, we fabricated electrospun polymer nanofibers containing light-reactive reduced graphene oxide (rGO) as part of a new classes of on-demand, electrically active biomaterials to enhance cell function. Fiber size, stiffness, and electrical conductivity varied with rGO concentration, which impacted hPSC-derived cardiomyocyte and neuron responses; with acute light stimulation, cardiomyocytes exhibited increased, synchronous calcium handling, and neurons showed more calcium peaks with higher frequency. Chronic, repetitive nanofiber light stimulation caused brain organoids to become increasingly electrically active and to activate photoreceptor pathways. This work outlines a tunable method where electrical cell functions can be titrated with rGO fibers and light stimulation, and it suggests that repetitive light stimulation may provide a novel method for retinal differentiation. HIGHLIGHTSO_LIElectrospun graphene-polymer nanofibers electrically respond to light stimulation C_LIO_LILight reactive graphene nanofibers stimulate electrically excitable cells in real-time C_LIO_LIStem cell-derived cardiomyocytes and neurons on nanofibers functionally improve C_LIO_LILight-training of brain organoids induces retinal and excitable neuron maturation C_LI

bioengineering↗

bioRxiv2021

In situ maturated early-stage human induced pluripotent stem cell-derived cardiomyocytes improve cardiac function by enhancing segmentary contraction in infarcted rats

The scant ability of cardiomyocytes to proliferate makes heart regeneration one of the biggest challenges of science. Current therapies do not contemplate heart re-muscularization. In this scenario, stem cell-based approaches have been proposed to overcome the lack of regeneration. We hypothesize PluriCell hiPSC-derived cardiomyocytes (hiPSC-CMs) could enhance rats cardiac function after myocardial infarction (MI). Animals were subjected to permanent occlusion of the Left-Ventricle (LV) anterior descending coronary artery (LAD). Seven days after MI, Early-stage hiPSC-CMs were injected intramyocardially. Rats were subjected to Echocardiography pre- and post-treatment. Thirty days after injections, treated rats displayed 6.2% human cardiac grafts, which were characterized molecularly. Left ventricle ejection fraction (LVEF) was improved by 7.8% in cell-injected rats, while placebo controls showed an 18.2% deterioration. Also, cell-treated rats displayed a 92% and 56% increase in radial and circumferential strains, respectively. Human cardiac grafts maturate in situ, preserving proliferation with 10% Ki67 and 3% PHH3 positive nuclei. Grafts were perfused by host vasculature with no evidence for immune rejection nor ectopic tissue formations. Our findings support PluriCell hiPSC-CMs as an alternative therapy to treat MI. The next steps of preclinical development include efficacy studies in large animals on the path to clinical-grade regenerative therapy targeting human patients.

physiology↗

bioRxiv2021

A cannabinoid receptor agonist shows anti-inflammatory and survival properties in human SARS-CoV-2-infected iPSC-derived cardiomyocytes

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can infect several organs, especially impacting respiratory capacity. Among the extrapulmonary manifestations of COVID-19 is myocardial injury, which is associated with a high risk of mortality. Myocardial injury, caused directly or indirectly by SARS-CoV-2 infection, can be triggered by inflammatory processes that cause damage to the heart tissue. Since one of the hallmarks of severe COVID-19 is the "cytokine storm", strategies to control inflammation caused by SARS-CoV-2 infection have been considered. Cannabinoids are known to have anti-inflammatory properties by negatively modulating the release of pro-inflammatory cytokines. Herein, we investigated the effects of the cannabinoid agonist WIN 55,212-2 (WIN) in human iPSC-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2. WIN did not modify angiotensin-converting enzyme II protein levels, nor reduced viral infection and replication in hiPSC-CMs. On the other hand, WIN reduced the levels of interleukins 6, 8, 18 and tumor necrosis factor-alpha (TNF-) released by infected cells, and attenuated cytotoxic damage measured by the release of lactate dehydrogenase (LDH). Our findings suggest that cannabinoids should be further explored as a complementary therapeutic tool for reducing inflammation in COVID-19 patients.

cell biology↗

bioRxiv2021

Inhibition of SARS-CoV-2 infection in human cardiomyocytes by targeting the Sigma-1 receptor disrupts cytoskeleton architecture and contractility

Heart dysfunction, represented by conditions such as myocarditis and arrhythmia, has been reported in COVID-19 patients. Therapeutic strategies focused on the cardiovascular system, however, remain scarce. The Sigma-1 receptor (S1R) has been recently proposed as a therapeutic target because its inhibition reduces SARS-CoV-2 replication. To investigate the role of S1R in SARS-CoV-2 infection in the heart, we used human cardiomyocytes derived from induced pluripotent stem cells (hiPSC-CM) as an experimental model. Here we show that the S1R antagonist NE-100 decreases SARS-CoV-2 infection and viral replication in hiPSC-CMs. Also, NE-100 reduces cytokine release and cell death associated with infection. Because S1R is involved in cardiac physiology, we investigated the effects of NE-100 in cardiomyocyte morphology and function. We show that NE-100 compromises cytoskeleton integrity and reduces beating frequency, causing contractile impairment. These results show that targeting S1R to challenge SARS-CoV-2 infection may be a useful therapeutic strategy but its detrimental effects in vivo on cardiac function should not be ignored.

cell biology↗