A5051986223- CRISPR and Genetic Engineering
- Muscle Physiology and Disorders
- Virus-based gene therapy research
- Cardiac Ischemia and Reperfusion
- Mechanical Circulatory Support Devices
- Mesenchymal stem cell research
- Tissue Engineering and Regenerative Medicine
- Neuroscience and Neural Engineering
- Cancer, Hypoxia, and Metabolism
- Electrospun Nanofibers in Biomedical Applications
- Pluripotent Stem Cells Research
- Hemoglobin structure and function
- Viral Infectious Diseases and Gene Expression in Insects
- Neurogenetic and Muscular Disorders Research
- Heme Oxygenase-1 and Carbon Monoxide
- Carbon Nanotubes in Composites
- Molecular Biology Techniques and Applications
- RNA Interference and Gene Delivery
- Dental Implant Techniques and Outcomes
- Facial Trauma and Fracture Management
- MicroRNA in disease regulation
- RNA modifications and cancer
- Anesthesia and Neurotoxicity Research
- Mitochondrial Function and Pathology
- Polymer Nanocomposite Synthesis and Irradiation
Jagiellonian University
2016-2024
University Medical Center Groningen
2024
Aims: Muscle damage in Duchenne muscular dystrophy (DMD) caused by the lack of dystrophin is strongly linked to inflammation. Heme oxygenase-1 (HO-1; Hmox1) an anti-inflammatory and cytoprotective enzyme affecting myoblast differentiation inhibiting myomiRs. The role HO-1 has not been so far well addressed DMD. Results: In dystrophin-deficient mdx mice, expression Hmox1 limb skeletal muscles diaphragm higher than wild-type animals, being consistently elevated from 8 up 52 weeks, both...
Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disease. Although it leads to muscle weakness, affected individuals predominantly die from cardiomyopathy, which remains uncurable. Accumulating evidence suggests that an overexpression of utrophin may counteract some the pathophysiological outcomes DMD. The aim this study was investigate role in dystrophin-deficient human cardiomyocytes (CMs) and test whether utrophin, implemented via CRISPR-deadCas9-VP64 system, can improve their...
Cell therapies are extensively tested to restore heart function after myocardial infarction (MI). Survival of any cell type intracardiac administration, however, may be limited due unfavorable conditions damaged tissue. Therefore, the aim this study was evaluate therapeutic effect adipose-derived stromal cells (ADSCs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) overexpressing either proangiogenic SDF-1α or anti-inflammatory heme oxygenase-1 (HO-1) in a murine...
Abstract Aims Duchenne muscular dystrophy (DMD)-associated cardiomyopathy is a serious life-threatening complication, the mechanisms of which have not been fully established, and therefore no effective treatment currently available. The purpose study was to identify new molecular signatures development in DMD. Methods results For modelling DMD-associated cardiomyopathy, we prepared three pairs isogenic control dystrophin-deficient human induced pluripotent stem cell (hiPSC) lines. Two hiPSC...
Doxorubicin (DOX) is a widely used anticancer drug. However, its clinical use severely limited due to drug-induced cumulative cardiotoxicity, which leads progressive cardiomyocyte dysfunction and heart failure. Enormous efforts have been made identify potential strategies alleviate DOX-induced cardiotoxicity; however, date, no universal highly effective therapy has introduced. Here we reported that cinnamic acid (CA) derivatives exert multitarget protective effect against cardiotoxicity. The...
Duchenne muscular dystrophy (DMD), caused by a lack of functional dystrophin, is characterized progressive muscle degeneration. Interestingly, dystrophin also expressed in endothelial cells (ECs), and insufficient angiogenesis has already been hypothesized to contribute DMD pathology, however, its status mdx mice, model DMD, still not fully clear. Our study aimed reveal angiogenesis-related alterations skeletal muscles mice compared wild-type (WT) counterparts. By investigating 6-...
Systemically delivered adeno-associated viral vector serotype 9 (AAV9) effectively transduces murine heart, but provides transgene expression also in liver and skeletal muscles. Improvement of the selectivity can be achieved through incorporation target sites (TSs) for miRNA-122 miRNA-206 into 3' untranslated region (3' UTR) cassette. Here, we aimed to generate such miRNA-122- miRNA-206-regulated AAV9 a therapeutic, heart-specific overexpression heme oxygenase-1 (HO-1). We successfully...
So far, the mechanisms that impede AAV transduction, especially in human heart, are poorly understood, hampering introduction of new, effective gene therapy strategies. Therefore, aim this study was to identify and overcome main cellular barriers successful transduction using iPSC-derived cardiomyocytes (iPSC-CMs), cardiac fibroblasts (iPSC-CFs), primary endothelial cells (HAECs) model vector-host interactions. Through phosphoproteome analysis we established casein kinase 2 (CK2) signalling...
Elevated expression of heme oxygenase-1 (HO-1, encoded by HMOX1) is observed in various types tumors. Hence, it suggested that HO-1 may serve as a potential target anticancer therapies. A novel approach to inhibit related the synthetic lethality this enzyme and fumarate hydratase (FH). In current study, we aimed validate effect genetic pharmacological inhibition cells isolated from patients suffering hereditary leiomyomatosis renal cell carcinoma (HLRCC)-an inherited cancer syndrome, caused...
Heme oxygenase-1 (HO-1, encoded by HMOX1) is a cytoprotective enzyme degrading heme into CO, Fe2+, and biliverdin. HO-1 was demonstrated to affect cardiac differentiation of murine pluripotent stem cells (PSCs), regulate the metabolism adult cardiomyocytes, influence regeneration infarcted myocardium in mice. However, enzyme’s effect on human cardiogenesis cardiomyocytes’ electromechanical properties has not been described so far. Thus, this study aimed investigate role induced (hiPSCs)...
Abstract Background/Purpose: Phospholamban (PLN) p.Arg14del (R14del, R14Δ/+) is a pathogenic variant that can cause cardiomyopathy, characterized by PLN protein aggregation, ultimately leading to heart failure (HF). The exact pathophysiology unknown, we aim uncover R14Δ/+ disease mechanisms and study potential treatment using antisense oligonucleotides (PLN-ASOs). Methods Phosphoproteomics was performed on human tissue from end-stage patients (N=6) versus other etiologies of HF (N=10) as...
Abstract Background Impaired muscle regeneration is a hallmark of Duchenne muscular dystrophy (DMD), neuromuscular disorder caused by mutations in the DMD gene encoding dystrophin. The lack heme oxygenase-1 (HO-1, Hmox1) , known anti-inflammatory and cytoprotective enzyme, was shown to aggravate pathology. Methods We evaluated role HO-1 overexpression human induced pluripotent stem cell (hiPSC)-derived skeletal cells (hiPSC-SkM) vitro process vivo wild-type mice. Furthermore, effect cobalt...
Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main source(s): Faculty Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Young scientists grant MNS9/2021 Polish Science Centre PRELUDIUM 2019/33/N/NZ1/03066 Introduction Although gene therapy has become a feasible alternative to regular treatment in numerous disorders, efficient targeting human heart still seems out reach. So far, adeno-associated viral vectors (AAVs) have...
too low to efficiently compensate for the loss of functional myocardium in heart disease.We hypothesize that cardiomyocyte proliferation is tightly controlled by regulatory mechanisms can be reactivated promote endogenous repair after injuries.Unequivocal identification cycling cardiomyocytes a fundamental requirement investigation these mechanisms.Methods: We used preexisting transgenic mouse model based on FUCCI (Fluorescent Ubiquitination-based Cell Cycle Indicator) system discriminate...
Abstract Introduction Despite progress in pharmacological treatment of myocardial infarction (MI), there is still an immense need for novel therapies this life-threatening condition. Accordingly, cell-based have been extensively investigated with most studies focusing on mesenchymal stromal cells. However due to their inability differentiate into cardiomyocytes as well limited survival upon vivo administration, no effective MI has developed. In contrast, application hiPSC-derived (hiPSC-CM)...
Spinal Muscular Atrophy (SMA) is a genetic neuromuscular disease caused by mutations inSMN1 gene encoding survival motor neuron (SMN) protein. Lack of this protein leads to progressive loss neurons and therefore gradual signal transmission between skeletal muscle cells. As consequence, patients develop atrophy lose the ability move independently, what also related problems with breathing swallowing. Here, we describe generation human induced pluripotent stem cells (hiPSC) from peripheral...