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Article ; Online: A procedure for in vitro evaluation of the immunosuppressive effect of mouse mesenchymal stem cells on activated T cell proliferation.

Marinescu, Catalina-Iolanda / Preda, Mihai Bogdan / Burlacu, Alexandrina

2021 Volume 12, Issue 1, Page(s) 319

Abstract: Background: Mesenchymal stem/stromal cells (MSC) represent adult cells with multipotent capacity. Besides their capacity to differentiate into multiple lineages in vitro and in vivo, increasing evidence points towards the immunomodulatory capacity of ... ...

Abstract	Background: Mesenchymal stem/stromal cells (MSC) represent adult cells with multipotent capacity. Besides their capacity to differentiate into multiple lineages in vitro and in vivo, increasing evidence points towards the immunomodulatory capacity of these cells, as an important feature for their therapeutic power. Although not included in the minimal criteria established by the International Society for Cellular Therapy as a defining MSC attribute, demonstration of the immunomodulatory capacity of MSC can be useful for the characterization of these cells before being considered MSC. Methods: Here we present a simple and reliable protocol by which the immunosuppressive effect of mouse bone marrow-derived MSC can be evaluated in vitro. It is based on the measuring of the proliferation of activated T cells cultured in direct contact with irradiated MSC. Results: Our results showed that mouse MSC have a dose-dependent inhibitory effect on activated T cell proliferation, which can be quantified as a percentage of maximum proliferation. Our data shows that batch-to-batch variability can be determined within one or multiple experiments, by extracting the area under curve of T cell proliferation plotted against the absolute number of MSC in co-culture. Conclusions: The validation of the immunosupressive capacity of MSC could be added to the characterization of the cells before being used in various MSC-based approaches to treat immunological diseases. Our results showed that mouse MSC have a dose-dependent inhibitory effect on activated T cell proliferation. The immunosuppressive properties of MSC vary between batches, but not between different passages of the same batch.
Language	English
Publishing date	2021-06-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-021-02344-3
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Article ; Online: Evolution of journal clubs: fostering collaborative learning in modern research.

Balamurali, Deepak / Preda, Mihai Bogdan / Ben-Aicha, Soumaya / Martino, Fabiana / Palioura, Dimitra / Kocken, Jordy M M / Emanueli, Costanza / Devaux, Yvan

European heart journal. Digital health

2024 Volume 5, Issue 2, Page(s) 195–197

Abstract: Journal clubs have been a staple in scientific communities, facilitating discussions on recent publications. However, the overwhelming volume of biomedical information poses a challenge in literature selection. This article provides an overview of ... ...

Abstract	Journal clubs have been a staple in scientific communities, facilitating discussions on recent publications. However, the overwhelming volume of biomedical information poses a challenge in literature selection. This article provides an overview of journal club types and their efficacy in training potential peer reviewers, enhancing communication skills, and critical thinking. Originating in the 19th century, journal clubs have evolved from traditional in-person meetings to virtual or hybrid formats, accelerated by the COVID-19 pandemic. Face-to-face interactions offer personal connections, while virtual events ensure wider participation and accessibility. Organizing journal clubs demands effort, but it has several benefits, including promoting new publications and providing a platform for meaningful discussions. The virtual CardioRNA J-club experience exemplifies successful multidisciplinary collaboration, fostering international connections and inspiring new research. Journal clubs remain a vital component of academic research, equipping senior researchers with the latest developments and nurturing the next generation of scientists. As millennial and Gen Z researchers join the scientific field, journal clubs continue to evolve as a fertile ground for education and collaborative learning in an ever-changing scientific landscape.
Language	English
Publishing date	2024-01-17
Publishing country	England
Document type	Journal Article
ISSN	2634-3916
ISSN (online)	2634-3916
DOI	10.1093/ehjdh/ztae003
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Article ; Online: A standard procedure for lentiviral-mediated labeling of murine mesenchymal stromal cells in vitro.

Lupan, Ana-Mihaela / Preda, Mihai Bogdan / Burlacu, Alexandrina

Biotechnology and applied biochemistry

2019 Volume 66, Issue 4, Page(s) 643–653

Abstract: Tracking of stem cells after transplantation is effectively performed in vivo with imaging systems, assuming the cells are adequately labeled to facilitate their recognition. This study aimed to optimize a protocol for fluorescent labeling of mesenchymal ...

Abstract	Tracking of stem cells after transplantation is effectively performed in vivo with imaging systems, assuming the cells are adequately labeled to facilitate their recognition. This study aimed to optimize a protocol for fluorescent labeling of mesenchymal stromal cells (MSCs) in vitro, by using a third-generation lentiviral system. Basically, 293T cells are seeded in high-glucose Dulbecco's modified Eagle medium with 10% FBS one day before transfection. Transfection is done for 24 h using a mix of transfer, packaging, regulatory, and envelope plasmids, in molar ratio of 4:2:1:1, respectively. After transfection, the cells are further cultured for two days. During this period, the viral medium is harvested two times, at 24-h intervals, with the first round being stored at 4°C until the second round is completed. The pooled viral medium is frozen in single-use aliquots. MSCs are transduced with 25 multiplicity of infection (MOI) and one day later the cells are passaged at standard seeding density and further grown for three days, when the fluorescence reach the maximum level. Our protocol provides particular experimental details for permanent MSC labeling that makes the procedure highly effective for therapeutic purposes, without affecting the functional properties of stem cells.
MeSH term(s)	Animals ; HEK293 Cells ; Humans ; Lentivirus/isolation & purification ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/virology ; Mice ; Mice, Inbred C57BL
Language	English
Publishing date	2019-05-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	883433-7
ISSN	1470-8744 ; 0885-4513
ISSN (online)	1470-8744
ISSN	0885-4513
DOI	10.1002/bab.1765
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Article ; Online: Identification of a Hematopoietic Cell Population Emerging From Mouse Bone Marrow With Proliferative Potential

Marinescu, Catalina-Iolanda / Preda, Mihai Bogdan / Neculachi, Carmen Alexandra / Rusu, Evelyn Gabriela / Popescu, Sinziana / Burlacu, Alexandrina

Frontiers in immunology

2021 Volume 12, Page(s) 698070

Abstract: There is continuing interest in therapeutic applications of bone marrow-derived mesenchymal stromal cells (MSC). Unlike human counterparts, mouse MSC are difficult to ... ...

Abstract	There is continuing interest in therapeutic applications of bone marrow-derived mesenchymal stromal cells (MSC). Unlike human counterparts, mouse MSC are difficult to propagate
MeSH term(s)	Animals ; Bone Marrow Cells/cytology ; Bone Marrow Cells/immunology ; Cell Proliferation ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/immunology ; Heterografts ; Humans ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/immunology ; Mice ; Mice, Inbred C57BL
Language	English
Publishing date	2021-08-03
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.698070
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Article ; Online: Dual Stem Cell Therapy Improves the Myocardial Recovery Post-Infarction through Reciprocal Modulation of Cell Functions.

Popescu, Sinziana / Preda, Mihai Bogdan / Marinescu, Catalina Iolanda / Simionescu, Maya / Burlacu, Alexandrina

International journal of molecular sciences

2021 Volume 22, Issue 11

Abstract: Mesenchymal stromal cells (MSC) are promising candidates for regenerative therapy of the infarcted heart. However, poor cell retention within the transplantation site limits their potential. We hypothesized that MSC benefits could be enhanced through a ... ...

Abstract	Mesenchymal stromal cells (MSC) are promising candidates for regenerative therapy of the infarcted heart. However, poor cell retention within the transplantation site limits their potential. We hypothesized that MSC benefits could be enhanced through a dual-cell approach using jointly endothelial colony forming cells (ECFC) and MSC. To assess this, we comparatively evaluated the effects of the therapy with MSC and ECFC versus MSC-only in a mouse model of myocardial infarction. Heart function was assessed by echocardiography, and the molecular crosstalk between MSC and ECFC was evaluated in vitro through direct or indirect co-culture systems. We found that dual-cell therapy improved cardiac function in terms of ejection fraction and stroke volume. In vitro experiments showed that ECFC augmented MSC effector properties by increasing Connexin 43 and Integrin alpha-5 and the secretion of healing-associated molecules. Moreover, MSC prompted the organization of ECFC into vascular networks. This indicated a reciprocal modulation in the functionality of MSC and ECFC. In conclusion, the crosstalk between MSC and ECFC augments the therapeutic properties of MSC and enhances the angiogenic properties of ECFC. Our data consolidate the dual-cell therapy as a step forward for the development of effective treatments for patients affected by myocardial infarction.
MeSH term(s)	Animals ; Endothelial Progenitor Cells/metabolism ; Endothelial Progenitor Cells/pathology ; Endothelial Progenitor Cells/transplantation ; Female ; Heterografts ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/metabolism ; Mesenchymal Stem Cells/pathology ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Myocardial Infarction/metabolism ; Myocardial Infarction/pathology ; Myocardial Infarction/physiopathology ; Myocardial Infarction/therapy ; Myocardium/metabolism ; Myocardium/pathology ; Stroke Volume
Language	English
Publishing date	2021-05-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22115631
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Article ; Online: miRNAs generated from Meg3-Mirg locus are downregulated during aging.

Lupan, Ana-Mihaela / Rusu, Evelyn-Gabriela / Preda, Mihai Bogdan / Marinescu, Catalina Iolanda / Ivan, Cristina / Burlacu, Alexandrina

Aging

2021 Volume 13, Issue 12, Page(s) 15875–15897

Abstract: Aging determines a multilevel functional decline and increases the risk for cardiovascular pathologies. MicroRNAs are recognized as fine tuners of all cellular functions, being involved in various cardiac diseases. The heart is one of the most affected ... ...

Abstract	Aging determines a multilevel functional decline and increases the risk for cardiovascular pathologies. MicroRNAs are recognized as fine tuners of all cellular functions, being involved in various cardiac diseases. The heart is one of the most affected organs in aged individuals, however little is known about the extent and robustness to which miRNA profiles are modulated in cardiac cells during aging. This paper provides a comprehensive characterization of the aging-associated miRNA profile in the murine cardiac fibroblasts, which are increasingly recognized for their active involvement in the cardiac physiology and pathology. Next-generation sequencing of cardiac fibroblasts isolated from young and old mice revealed that an important fraction of the miRNAs generated by the Meg3-Mirg locus was downregulated during aging. To address the specificity of this repression, four miRNAs selected as representative for this locus were further assessed in other cells and organs isolated from aged mice. The results suggested that the repression of miRNAs generated by the Meg3-Mirg locus was a general feature of aging in multiple organs. Bioinformatic analysis of the predicted target genes identified Integrin Beta-2 as an aged-upregulated gene, which was thereafter confirmed in multiple mouse organs. In conclusion, our study provides new data concerning the mechanisms of natural aging and highlights the robustness of the miRNA modulation during this process.
MeSH term(s)	Aging/genetics ; Animals ; Down-Regulation/genetics ; Fibroblasts/metabolism ; Gene Expression Profiling ; Genetic Loci ; Genome ; High-Throughput Nucleotide Sequencing ; Mice, Inbred C57BL ; MicroRNAs/genetics ; Multigene Family ; Myocardium/cytology ; Myocytes, Cardiac/metabolism ; Organ Specificity/genetics ; Up-Regulation/genetics ; Mice
Chemical Substances	MicroRNAs
Language	English
Publishing date	2021-06-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.203208
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Article: MiR-29a Increase in Aging May Function as a Compensatory Mechanism Against Cardiac Fibrosis Through SERPINH1 Downregulation.

Rusu-Nastase, Evelyn Gabriela / Lupan, Ana-Mihaela / Marinescu, Catalina Iolanda / Neculachi, Carmen Alexandra / Preda, Mihai Bogdan / Burlacu, Alexandrina

Frontiers in cardiovascular medicine

2022 Volume 8, Page(s) 810241

Abstract: Deregulation of microRNA (miRNA) profile has been reportedly linked to the aging process, which is a dominant risk factor for many pathologies. Among the miRNAs with documented roles in aging-related cardiac diseases, miR-18a, -21a, -22, and -29a were ... ...

Abstract	Deregulation of microRNA (miRNA) profile has been reportedly linked to the aging process, which is a dominant risk factor for many pathologies. Among the miRNAs with documented roles in aging-related cardiac diseases, miR-18a, -21a, -22, and -29a were mainly associated with hypertrophy and/or fibrosis; however, their relationship to aging was not fully addressed before. The purpose of this paper was to evaluate the variations in the expression levels of these miRNAs in the aging process. To this aim, multiple organs were harvested from young (2-3-months-old), old (16-18-months-old), and very old (24-25-months-old) mice, and the abundance of the miRNAs was evaluated by quantitative real-time (RT)-PCR. Our studies demonstrated that miR-21a, miR-22, and miR-29a were upregulated in the aged heart. Among them, miR-29a was highly expressed in many other organs, i.e., the brain, the skeletal muscle, the pancreas, and the kidney, and its expression was further upregulated during the natural aging process. Western blot, immunofluorescence, and xCELLigence analyses concurrently indicated that overexpression of miR-29a in the muscle cells decreased the collagen levels as well as cell migration and proliferation. Computational prediction analysis and overexpression studies identified SERPINH1, a specific chaperone of procollagens, as a potential miR-29a target. Corroborating to this, significantly downregulated SERPINH1 levels were found in the skeletal muscle, the heart, the brain, the kidney, and the pancreas harvested from very old animals, thereby indicating the role of the miR-29a-SERPINH1 axis in the aging process.
Language	English
Publishing date	2022-01-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2021.810241
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Article ; Online: Short lifespan of syngeneic transplanted MSC is a consequence of in vivo apoptosis and immune cell recruitment in mice.

Preda, Mihai Bogdan / Neculachi, Carmen Alexandra / Fenyo, Ioana Madalina / Vacaru, Ana-Maria / Publik, Mihai Alin / Simionescu, Maya / Burlacu, Alexandrina

Cell death & disease

2021 Volume 12, Issue 6, Page(s) 566

Abstract: Mesenchymal stromal cells (MSC) are attractive tools for cell-based therapy, yet the mechanisms underlying their migration and survival post-transplantation are unclear. Accumulating evidence indicates that MSC apoptosis modulates both innate and ... ...

Abstract	Mesenchymal stromal cells (MSC) are attractive tools for cell-based therapy, yet the mechanisms underlying their migration and survival post-transplantation are unclear. Accumulating evidence indicates that MSC apoptosis modulates both innate and adaptive immune responses which impact on MSC therapeutic effects. Using a dual tracking system, namely the Luciferase expression and VivoTrack680 labelling, and in vivo optical imaging, we investigated the survival and migration of MSC transplanted by various routes (intravenous, subcutaneous, intrapancreatic and intrasplenic) in order to identify the best delivery approach that provides an accumulation of therapeutic cells to the injured pancreas in the non-obese diabetic (NOD) mouse. The results showed that transplanted MSC had limited migration capacity, irrespective of the administration route, and were short-lived with almost total disappearance at 7 days after transplantation. Within one day after transplantation, cells activated hypoxia signalling pathways, followed by Caspase 3-mediated apoptosis. These were subsequently followed by local recruitment of immune cells at the transplantation site, and the engulfment of apoptotic MSC by macrophages. Our results argue for a "hit and die" mechanism of transplanted MSC. Further investigations will elucidate the molecular crosstalk between the inoculated and the host-immune cells.
MeSH term(s)	Animals ; Apoptosis ; Cell- and Tissue-Based Therapy/methods ; Mesenchymal Stem Cell Transplantation/methods ; Mesenchymal Stem Cells/metabolism ; Mice ; Mice, Inbred NOD
Language	English
Publishing date	2021-06-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-021-03839-w
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Article ; Online: Evaluation of gene and cell-based therapies for cardiac regeneration.

Preda, Mihai Bogdan / Valen, Guro

Current stem cell research & therapy

2013 Volume 8, Issue 4, Page(s) 304–312

Abstract: Although the treatment of acute myocardial infarction has improved considerably and the mortality rate is reduced, patients who survive may develop loss of cardiomyocytes, scar formation, ventricular remodeling, and ultimately heart failure. The ... ...

Abstract	Although the treatment of acute myocardial infarction has improved considerably and the mortality rate is reduced, patients who survive may develop loss of cardiomyocytes, scar formation, ventricular remodeling, and ultimately heart failure. The treatment of the most severe types of heart failure is heart transplantation, but this therapeutic intervention is not available for a large number of patients due to a shortage of donor hearts. Since current pharmacological and interventional approaches are unsuccessful to regenerate infarcted myocardium, new approaches like gene- or cell-based therapies are tested to prevent loss of cardiac tissue, enhance angiogenesis, and to reduce left ventricular remodeling. Exciting and promising data on laboratory animals have moved the field rapidly into clinical trials. Although several clinical trials proved the safety and feasibility of using gene- and cell-based therapies, many challenges remain before large-scale novel treatment modules will be available. The purpose of this review is to summarize the key findings of larger, randomized clinical trials in cardiovascular medicine using both gene and cell-based therapy, and to emphasize the most significant questions that emerged from the clinical experience so far, such as the optimal gene or cell type to be used, the ideal delivery route, and for DNA the ideal delivery system. Understanding the mechanisms of gene- and cell-based therapies is essential for designing the next phase clinical studies in the field of regenerative medicine.
MeSH term(s)	Animals ; Clinical Trials as Topic ; Coronary Artery Disease/therapy ; Genetic Therapy ; Heart/growth & development ; Heart/physiopathology ; Humans ; Myocardial Infarction/therapy ; Regenerative Medicine ; Stem Cell Transplantation
Language	English
Publishing date	2013-04-02
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	2251937-3
ISSN	2212-3946 ; 1574-888X
ISSN (online)	2212-3946
ISSN	1574-888X
DOI	10.2174/1574888x11308040006
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Article ; Online: The science behind soft skills: Do's and Don'ts for early career researchers and beyond. A review paper from the EU-CardioRNA COST Action CA17129.

Acharya, Shubhra / Preda, Mihai Bogdan / Papatheodorou, Ioanna / Palioura, Dimitra / Giardoglou, Panagiota / Tsata, Vasiliki / Erceg, Sanja / Barbalata, Teodora / Ben-Aicha, Soumaya / Martino, Fabiana / Nicastro, Laura / Lazou, Antigone / Beis, Dimitris / Martelli, Fabio / Sopic, Miron / Emanueli, Costanza / Kardassis, Dimitris / Devaux, Yvan

Open research Europe

2023 Volume 3, Page(s) 55

Abstract: Soft skills are the elementary management, personal, and interpersonal abilities that are vital for an individual to be efficient at workplace or in their personal life. Each work place requires different set of soft skills. Thus, in addition to ... ...

Abstract	Soft skills are the elementary management, personal, and interpersonal abilities that are vital for an individual to be efficient at workplace or in their personal life. Each work place requires different set of soft skills. Thus, in addition to scientific/technical skills that are easier to access within a short time frame, several key soft skills are essential for the success of a researcher in today's international work environment. In this paper, the trainees and trainers of the EU-CardioRNA COST Action CA17129 training school on soft skills present basic and advanced soft skills for early career researchers. Here, we particularly emphasize on the importance of transferable and presentation skills, ethics, literature reading and reviewing, research protocol and grant writing, networking, and career opportunities for researchers. All these skills are vital but are often overlooked by some scholars. We also provide tips to ace in aforementioned skills that are crucial in a day-to-day life of early and late career researchers in academia and industry.
Language	English
Publishing date	2023-10-12
Publishing country	Belgium
Document type	Journal Article
ISSN	2732-5121
ISSN (online)	2732-5121
DOI	10.12688/openreseurope.15746.2
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