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Book: Microparticulate systems for the delivery of proteins and vaccines

Cohen, Smadar

(Drugs and the pharmaceutical sciences ; 77)

1996

Author's details	ed. by Smadar Cohen
Series title	Drugs and the pharmaceutical sciences ; 77
Collection
Keywords	Drug Carriers ; Drug Delivery Systems ; Drug Compounding ; Proteins / administration & dosage ; Vaccines / administration & dosage ; Impfstoff ; Mikroverkapselung ; Proteine ; Arzneimittel ; Mikrokapsel ; Kontrollierte Wirkstofffreisetzung
Subject	Verzögerte Freisetzung ; Fertigarzneimittel ; Therapeutikum ; Medikament ; Medukamente ; Pharmakon ; Pharmaka ; Arzneistoff ; Arzneimittelwirkstoff ; Arznei ; Pharmazeutikum ; Pharmazeutika ; Pharmazeutischer Wirkstoff ; Arzneidroge ; Eiweiss ; Protein ; Vaccine ; Vakzine ; Antikörperhaltiges Arzneimittel
Language	English
Size	IX, 525 S. : Ill., graph. Darst.
Edition	1. print.
Publisher	Dekker
Publishing place	New York u.a.
Publishing country	United States
Document type	Book
HBZ-ID	HT007399111
ISBN	0-8247-9753-1 ; 978-0-8247-9753-9
Database	Catalogue ZB MED Medicine, Health

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1997 A 289	order for loan	Magazin

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Article ; Online: 316Engineered extracellular vesicle-mediated delivery of miR-199a-3p increases the viability of 3D-printed cardiac patches.

Bar, Assaf / Kryukov, Olga / Etzion, Sharon / Cohen, Smadar

International journal of bioprinting

2023 Volume 9, Issue 2, Page(s) 670

Abstract: In recent years, extrusion-based three-dimensional (3D) bioprinting is employed for engineering cardiac patches (CP) due to its ability to assemble complex structures from hydrogel-based bioinks. However, the cell viability in such CPs is low due to ... ...

Abstract	In recent years, extrusion-based three-dimensional (3D) bioprinting is employed for engineering cardiac patches (CP) due to its ability to assemble complex structures from hydrogel-based bioinks. However, the cell viability in such CPs is low due to shear forces applied on the cells in the bioink, inducing cellular apoptosis. Herein, we investigated whether the incorporation of extracellular vesicles (EVs) in the bioink, engineered to continually deliver the cell survival factor miR-199a-3p would increase the viability within the CP. EVs from THP-1-derived activated macrophages (MΦ) were isolated and characterized by nanoparticle tracking analysis (NTA), cryogenic electron microscopy (cryo-TEM), and Western blot analysis. MiR-199a-3p mimic was loaded into EVs by electroporation after optimization of applied voltage and pulses. Functionality of the engineered EVs was assessed in neonatal rat cardiomyocyte (NRCM) monolayers using immunostaining for the proliferation markers ki67 and Aurora B kinase. To examine the effect of engineered EVs on 3D-bioprinted CP viability, the EVs were added to the bioink, consisting of alginate-RGD, gelatin, and NRCM. Metabolic activity and expression levels of activated-caspase 3 for apoptosis of the 3D-bioprinted CP were evaluated after 5 days. Electroporation (850 V with 5 pulses) was found to be optimal for miR loading; miR-199a-3p levels in EVs increased fivefold compared to simple incubation, with a loading efficiency of 21.0%. EV size and integrity were maintained under these conditions. Cellular uptake of engineered EVs by NRCM was validated, as 58% of cTnT
Language	English
Publishing date	2023-01-17
Publishing country	Singapore
Document type	Journal Article
ZDB-ID	2834694-4
ISSN	2424-8002 ; 2424-8002
ISSN (online)	2424-8002
ISSN	2424-8002
DOI	10.18063/ijb.v9i2.670
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Article: Inducing Endogenous Cardiac Regeneration: Can Biomaterials Connect the Dots?

Bar, Assaf / Cohen, Smadar

Frontiers in bioengineering and biotechnology

2020 Volume 8, Page(s) 126

Abstract: Heart failure (HF) after myocardial infarction (MI) due to blockage of coronary arteries is a major public health issue. MI results in massive loss of cardiac muscle due to ischemia. Unfortunately, the adult mammalian myocardium presents a low ... ...

Abstract	Heart failure (HF) after myocardial infarction (MI) due to blockage of coronary arteries is a major public health issue. MI results in massive loss of cardiac muscle due to ischemia. Unfortunately, the adult mammalian myocardium presents a low regenerative potential, leading to two main responses to injury: fibrotic scar formation and hypertrophic remodeling. To date, complete heart transplantation remains the only clinical option to restore heart function. In the last two decades, tissue engineering has emerged as a promising approach to promote cardiac regeneration. Tissue engineering aims to target processes associated with MI, including cardiomyogenesis, modulation of extracellular matrix (ECM) remodeling, and fibrosis. Tissue engineering dogmas suggest the utilization and combination of two key components: bioactive molecules and biomaterials. This chapter will present current therapeutic applications of biomaterials in cardiac regeneration and the challenges still faced ahead. The following biomaterial-based approaches will be discussed: Nano-carriers for cardiac regeneration-inducing biomolecules; corresponding matrices for their controlled release; injectable hydrogels for cell delivery and cardiac patches. The concept of combining cardiac patches with controlled release matrices will be introduced, presenting a promising strategy to promote endogenous cardiac regeneration.
Language	English
Publishing date	2020-02-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2719493-0
ISSN	2296-4185
ISSN	2296-4185
DOI	10.3389/fbioe.2020.00126
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Article ; Online: Temporal Control over Macrophage Phenotype and the Host Response via Magnetically Actuated Scaffolds.

Steele, Lindsay A / Spiller, Kara L / Cohen, Smadar / Rom, Slava / Polyak, Boris

ACS biomaterials science & engineering

2022 Volume 8, Issue 8, Page(s) 3526–3541

Abstract: Cyclic strain generated at the cell-material interface is critical for the engraftment of biomaterials. Mechanosensitive immune cells, macrophages regulate the host-material interaction immediately after implantation by priming the environment and ... ...

Abstract	Cyclic strain generated at the cell-material interface is critical for the engraftment of biomaterials. Mechanosensitive immune cells, macrophages regulate the host-material interaction immediately after implantation by priming the environment and remodeling ongoing regenerative processes. This study investigated the ability of mechanically active scaffolds to modulate macrophage function
MeSH term(s)	Animals ; Biocompatible Materials ; Macrophages/metabolism ; Mice ; Phenotype ; Tissue Scaffolds
Chemical Substances	Biocompatible Materials
Language	English
Publishing date	2022-07-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2373-9878
ISSN (online)	2373-9878
DOI	10.1021/acsbiomaterials.2c00373
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Article ; Online: Defining the timeline of periostin upregulation in cardiac fibrosis following acute myocardial infarction in mice.

Gil, Hadas / Goldshtein, Matan / Etzion, Sharon / Elyagon, Sigal / Hadad, Uzi / Etzion, Yoram / Cohen, Smadar

Scientific reports

2022 Volume 12, Issue 1, Page(s) 21863

Abstract: After myocardial infarction (MI), the heart's reparative response to the ischemic insult and the related loss of cardiomyocytes involves cardiac fibrosis, in which the damaged tissue is replaced with a fibrous scar. Although the scar is essential to ... ...

Abstract	After myocardial infarction (MI), the heart's reparative response to the ischemic insult and the related loss of cardiomyocytes involves cardiac fibrosis, in which the damaged tissue is replaced with a fibrous scar. Although the scar is essential to prevent ventricular wall rupture in the infarction zone, it expands over time to remote, non-infarct areas, significantly increasing the extent of fibrosis and markedly altering cardiac structure. Cardiac function in this scenario deteriorates, thereby increasing the probability of heart failure and the risk of death. Recent works have suggested that the matricellular protein periostin, known to be involved in fibrosis, is a candidate therapeutic target for the regulation of MI-induced fibrosis and remodeling. Different strategies for the genetic manipulation of periostin have been proposed previously, yet those works did not properly address the time dependency between periostin activity and cardiac fibrosis. Our study aimed to fill that gap in knowledge and fully elucidate the explicit timing of cellular periostin upregulation in the infarcted heart to enable the safer and more effective post-MI targeting of periostin-producing cells. Surgical MI was performed in C57BL/6J and BALB/c mice by ligation of the left anterior descending coronary artery. Flow cytometry analyses of cells derived from the infarcted hearts and quantitative real-time PCR of the total cellular RNA revealed that periostin expression increased during days 2-7 and peaked on day 7 post-infarct, regardless of mouse strain. The established timeline for cellular periostin expression in the post-MI heart is a significant milestone toward the development of optimal periostin-targeted gene therapy.
MeSH term(s)	Animals ; Mice ; Cicatrix/pathology ; Disease Models, Animal ; Fibrosis ; Mice, Inbred C57BL ; Myocardial Infarction/metabolism ; Myocardium/metabolism ; Myocytes, Cardiac/metabolism ; Up-Regulation ; Ventricular Remodeling/genetics
Chemical Substances	Postn protein, mouse
Language	English
Publishing date	2022-12-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-26035-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: PLEKHM2 Loss of Function Impairs the Activity of iPSC-Derived Neurons via Regulation of Autophagic Flux.

Ben-Zvi, Hadas / Rabinski, Tatiana / Ofir, Rivka / Cohen, Smadar / Vatine, Gad D

International journal of molecular sciences

2022 Volume 23, Issue 24

Abstract: Pleckstrin Homology And RUN Domain Containing M2 (PLEKHM2) [delAG] mutation causes dilated cardiomyopathy with left ventricular non-compaction (DCM-LVNC), resulting in a premature death of PLEKHM2[delAG] individuals due to heart failure. PLEKHM2 is a ... ...

Abstract	Pleckstrin Homology And RUN Domain Containing M2 (PLEKHM2) [delAG] mutation causes dilated cardiomyopathy with left ventricular non-compaction (DCM-LVNC), resulting in a premature death of PLEKHM2[delAG] individuals due to heart failure. PLEKHM2 is a factor involved in autophagy, a master regulator of cellular homeostasis, decomposing pathogens, proteins and other cellular components. Autophagy is mainly carried out by the lysosome, containing degradation enzymes, and by the autophagosome, which engulfs substances marked for decomposition. PLEKHM2 promotes lysosomal movement toward the cell periphery. Autophagic dysregulation is associated with neurodegenerative diseases' pathogenesis. Thus, modulation of autophagy holds considerable potential as a therapeutic target for such disorders. We hypothesized that PLEKHM2 is involved in neuronal development and function, and that mutated PLEKHM2 (PLEKHM2[delAG]) neurons will present impaired functions. Here, we studied PLEKHM2-related abnormalities in induced pluripotent stem cell (iPSC)-derived motor neurons (iMNs) as a neuronal model. PLEKHM2[delAG] iMN cultures had healthy control-like differentiation potential but exhibited reduced autophagic activity. Electrophysiological measurements revealed that PLEKHM2[delAG] iMN cultures displayed delayed functional maturation and more frequent and unsynchronized activity. This was associated with increased size and a more perinuclear lysosome cellular distribution. Thus, our results suggest that PLEKHM2 is involved in the functional development of neurons through the regulation of autophagic flux.
Language	English
Publishing date	2022-12-17
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/ijms232416092
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Article ; Online: Functional defects in hiPSCs-derived cardiomyocytes from patients with a PLEKHM2-mutation associated with dilated cardiomyopathy and left ventricular non-compaction.

Korover, Nataly / Etzion, Sharon / Cherniak, Alexander / Rabinski, Tatiana / Levitas, Aviva / Etzion, Yoram / Ofir, Rivka / Parvari, Ruti / Cohen, Smadar

Biological research

2023 Volume 56, Issue 1, Page(s) 34

Abstract: Dilated cardiomyopathy (DCM) is a primary myocardial disease, leading to heart failure and excessive risk of sudden cardiac death with rather poorly understood pathophysiology. In 2015, Parvari's group identified a recessive mutation in the autophagy ... ...

Abstract	Dilated cardiomyopathy (DCM) is a primary myocardial disease, leading to heart failure and excessive risk of sudden cardiac death with rather poorly understood pathophysiology. In 2015, Parvari's group identified a recessive mutation in the autophagy regulator, PLEKHM2 gene, in a family with severe recessive DCM and left ventricular non-compaction (LVNC). Fibroblasts isolated from these patients exhibited abnormal subcellular distribution of endosomes, Golgi apparatus, lysosomes and had impaired autophagy flux. To better understand the effect of mutated PLEKHM2 on cardiac tissue, we generated and characterized induced pluripotent stem cells-derived cardiomyocytes (iPSC-CMs) from two patients and a healthy control from the same family. The patient iPSC-CMs showed low expression levels of genes encoding for contractile functional proteins (α and β-myosin heavy chains and 2v and 2a-myosin light chains), structural proteins integral to heart contraction (Troponin C, T and I) and proteins participating in Ca
MeSH term(s)	Humans ; Calcium/metabolism ; Calcium/pharmacology ; Cardiomyopathy, Dilated/genetics ; Cardiomyopathy, Dilated/metabolism ; Cell Differentiation ; Induced Pluripotent Stem Cells ; Mutation ; Myocytes, Cardiac/metabolism
Chemical Substances	Calcium (SY7Q814VUP) ; SKIP enzyme, human (EC 3.1.3.-) ; PLEKHM2 protein, human
Language	English
Publishing date	2023-06-23
Publishing country	England
Document type	Journal Article
ZDB-ID	1138990-4
ISSN	0717-6287 ; 0716-9760
ISSN (online)	0717-6287
ISSN	0716-9760
DOI	10.1186/s40659-023-00442-5
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Article: Hypoxia-sensitive drug delivery to tumors

Filipczak, Nina / Joshi, Ujjwal / Attia, Sara Aly / Berger Fridman, Ilana / Cohen, Smadar / Konry, Tania / Torchilin, Vladimir

Journal of controlled release. 2022 Jan., v. 341

2022

Abstract: Achievement of a high dose of drug in the tumor while minimizing its systemic side effects is one of the important features of an improved drug delivery system. Thus, developing responsive carriers for site-specific delivery of chemotherapeutic agents ... ...

Abstract	Achievement of a high dose of drug in the tumor while minimizing its systemic side effects is one of the important features of an improved drug delivery system. Thus, developing responsive carriers for site-specific delivery of chemotherapeutic agents has become a main goal of research efforts. One of the known hallmarks of cancerous tumors is hypoxia, which offers a target for selective drug delivery. The stimuli-sensitive micellar system developed by us, (PEG-azobenzene-PEI-DOPE (PAPD) has proven to be effective in vitro. The proposed construct developed, PAPD, contains an azobenzene group as a hypoxia-sensitive moiety that triggers the shedding of the PEG layer from the nanoparticle surface under conditions of hypoxia to improve cellular uptake. Using microfluidics, we show significantly improved cellular association and penetration under hypoxia in both single cells and in a 3D tumor model. Employing an in vivo model, we demonstrate slower tumor growth that did not induce systemic side effects, including weight loss in an experimental animal model, when compared to the free drug treatment. This complex-in-nature but simple-in-design system for the simultaneous delivery of siRNA to silence the P-glycoprotein and doxorubicin with active tumor targeting and proven therapeutic efficacy represents a universal platform for the delivery of other hydrophobic chemotherapeutic agents and siRNA molecules which can be further modified.
Keywords	P-glycoproteins ; animal models ; doxorubicin ; drug delivery systems ; drug therapy ; hydrophobicity ; hypoxia ; laboratory animals ; microfluidic technology ; moieties ; neoplasms ; weight loss
Language	English
Dates of publication	2022-01
Size	p. 431-442.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2021.11.034
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: MiR-499 Responsive Lethal Construct for Removal of Human Embryonic Stem Cells after Cardiac Differentiation.

Elovic, Edan / Etzion, Sharon / Cohen, Smadar

Scientific reports

2019 Volume 9, Issue 1, Page(s) 14490

Abstract: Deriving cell populations from human embryonic stem cells (hESCs) for cell-based therapy is considered a promising strategy to achieve functional cells, yet its translation to clinical practice depends on achieving fully defined differentiated cells. In ... ...

Abstract	Deriving cell populations from human embryonic stem cells (hESCs) for cell-based therapy is considered a promising strategy to achieve functional cells, yet its translation to clinical practice depends on achieving fully defined differentiated cells. In this work, we generated a miRNA-responsive lethal mRNA construct that selectively induces rapid apoptosis in hESCs by expressing a mutant (S184del) Bax variant. Insertion of miR-499 target sites in the construct enabled to enrich hESC-derived cardiomyocytes (CMs) in culture. A deterministic non-linear model was developed and validated with experimental data, to predict the outcome for each treatment cycle and the number of treatment cycle repetitions required to achieve completely purified cTNT-positive cells. The enriched hESC-CMs displayed physiological sarcomere orientation, functional calcium handling and after transplantation into SCID-NOD mice did not form teratomas. The modular miRNA responsive lethal mRNA construct could be employed in additional directed differentiation protocols, by adjusting the miRNA to the specific cells of choice.
MeSH term(s)	Animals ; Apoptosis/genetics ; Cell Differentiation/genetics ; Cell Line ; Gene Expression Regulation, Developmental ; Genes, Lethal/genetics ; Genetic Vectors/genetics ; Human Embryonic Stem Cells/metabolism ; Humans ; Mice ; MicroRNAs/antagonists & inhibitors ; MicroRNAs/genetics ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/transplantation ; Organogenesis/genetics ; RNA, Messenger/genetics ; bcl-2-Associated X Protein/genetics
Chemical Substances	BAX protein, human ; MIRN499 microRNA, human ; MicroRNAs ; RNA, Messenger ; bcl-2-Associated X Protein
Language	English
Publishing date	2019-10-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-50899-2
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Article ; Online: High throughput microfluidic system with multiple oxygen levels for the study of hypoxia in tumor spheroids.

Berger Fridman, Ilana / Ugolini, Giovanni Stefano / VanDelinder, Virginia / Cohen, Smadar / Konry, Tania

Biofabrication

2021 Volume 13, Issue 3

Abstract: Replication of physiological oxygen levels is fundamental for modeling human physiology and pathology ... ...

Abstract	Replication of physiological oxygen levels is fundamental for modeling human physiology and pathology in
MeSH term(s)	Breast Neoplasms ; Cell Line, Tumor ; Doxorubicin ; Female ; Humans ; Hypoxia ; Microfluidics ; Oxygen ; Spheroids, Cellular
Chemical Substances	Doxorubicin (80168379AG) ; Oxygen (S88TT14065)
Language	English
Publishing date	2021-04-26
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2500944-8
ISSN	1758-5090 ; 1758-5082
ISSN (online)	1758-5090
ISSN	1758-5082
DOI	10.1088/1758-5090/abdb88
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