Dissolvable microgel-templated macroporous hydrogels for controlled cell assembly

Mesenchymal stem cells (MSCs)-based therapies have been widely used to promote tissue regeneration and to modulate immune/inflammatory response. The therapeutic potential of MSCs can be further improved by forming multi-cellular spheroids. Meanwhile, hydrogels with macroporous structures are advantageous for improving mass transport properties for the cell-laden matrices. Herein, we report the fabrication of MSC-laden macroporous hydrogel scaffolds through incorporating rapidly dissolvable spherical cell-laden microgels. Dissolvable microgels were fabricated by tandem droplet-microfluidics and thiol-norbornene photopolymerization using a novel fast-degrading macromer poly(ethylene glycol)-norbornene-dopamine (PEGNB-Dopa). The cell-laden microgels were subsequently encapsulated within another bulk hydrogel matrix, whose porous structure was generated efficiently by the rapid degradation of the PEGNB-Dopa microgels. The cytocompatibility of this in situ pore-forming approach was demonstrated with multiple cell types. Furthermore, adjusting the stiffness and cell adhesiveness of the bulk hydrogels afforded the formation of solid cell spheroids or hollow spheres. The assembly of solid or hollow MSC spheroids led to differential activation of AKT pathway. Finally, MSCs solid spheroids formed in situ within the macroporous hydrogels exhibited robust secretion of HGF, VEGF-A, IL-6, IL-8, and TIMP-2. In summary, this platform provides an innovative method for forming cell-laden macroporous hydrogels for a variety of future biomedical applications.

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Therapeutic Potential of Umbilical Cord Stem Cells for Liver Regeneration

Current Stem Cell Research & Therapy ◽

10.2174/1568026620666200220122536 ◽

2020 ◽

Vol 15 (3) ◽

pp. 219-232

Author(s):

Ifrah Anwar ◽

Usman A. Ashfaq ◽

Zeeshan Shokat

Keyword(s):

Stem Cells ◽

Umbilical Cord ◽

Fas Ligand ◽

Viral Infections ◽

Therapeutic Potential ◽

Cell Types ◽

Low Risk ◽

Blood Stem Cells ◽

Umbilical Cord Stem Cells ◽

High Regeneration

The liver is a vital organ for life and the only internal organ that is capable of natural regeneration. Although the liver has high regeneration capacity, excessive hepatocyte death can lead to liver failure. Various factors can lead to liver damage including drug abuse, some natural products, alcohol, hepatitis, and autoimmunity. Some models for studying liver injury are APAP-based model, Fas ligand (FasL), D-galactosamine/endotoxin (Gal/ET), Concanavalin A, and carbon tetrachloride-based models. The regeneration of the liver can be carried out using umbilical cord blood stem cells which have various advantages over other stem cell types used in liver transplantation. UCB-derived stem cells lack tumorigenicity, have karyotype stability and high immunomodulatory, low risk of graft versus host disease (GVHD), low risk of transmitting somatic mutations or viral infections, and low immunogenicity. They are readily available and their collection is safe and painless. This review focuses on recent development and modern trends in the use of umbilical cord stem cells for the regeneration of liver fibrosis.

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In situ differentiation of iridophore crystallotypes underlies zebrafish stripe patterning

Nature Communications ◽

10.1038/s41467-020-20088-1 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Dvir Gur ◽

Emily J. Bain ◽

Kory R. Johnson ◽

Andy J. Aman ◽

H. Amalia Pasoili ◽

...

Keyword(s):

Skin Color ◽

Cell Types ◽

Color Pattern ◽

Single Type ◽

Sequencing Analysis ◽

X Ray Diffraction ◽

X Ray ◽

Cryogenic Scanning Electron Microscopy ◽

Different Cell Types

AbstractSkin color patterns are ubiquitous in nature, impact social behavior, predator avoidance, and protection from ultraviolet irradiation. A leading model system for vertebrate skin patterning is the zebrafish; its alternating blue stripes and yellow interstripes depend on light-reflecting cells called iridophores. It was suggested that the zebrafish’s color pattern arises from a single type of iridophore migrating differentially to stripes and interstripes. However, here we find that iridophores do not migrate between stripes and interstripes but instead differentiate and proliferate in-place, based on their micro-environment. RNA-sequencing analysis further reveals that stripe and interstripe iridophores have different transcriptomic states, while cryogenic-scanning-electron-microscopy and micro-X-ray diffraction identify different crystal-arrays architectures, indicating that stripe and interstripe iridophores are different cell types. Based on these results, we present an alternative model of skin patterning in zebrafish in which distinct iridophore crystallotypes containing specialized, physiologically responsive, organelles arise in stripe and interstripe by in-situ differentiation.

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Poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate) Copolymers for the Formulation of In Situ Forming Depot Long-Acting Injectables

Pharmaceutics ◽

10.3390/pharmaceutics13050605 ◽

2021 ◽

Vol 13 (5) ◽

pp. 605

Author(s):

Marie-Emérentienne Cagnon ◽

Silvio Curia ◽

Juliette Serindoux ◽

Jean-Manuel Cros ◽

Feifei Ng ◽

...

Keyword(s):

Ethylene Glycol ◽

Surface Erosion ◽

Sustained Delivery ◽

Trimethylene Carbonate ◽

Poly Ethylene Glycol ◽

In Situ Forming ◽

Poly Ethylene ◽

Long Acting

This article describes the utilization of (methoxy)poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate) ((m)PEG–PTMC) diblock and triblock copolymers for the formulation of in situ forming depot long-acting injectables by solvent exchange. The results shown in this manuscript demonstrate that it is possible to achieve long-term drug deliveries from suspension formulations prepared with these copolymers, with release durations up to several months in vitro. The utilization of copolymers with different PEG and PTMC molecular weights affords to modulate the release profile and duration. A pharmacokinetic study in rats with meloxicam confirmed the feasibility of achieving at least 28 days of sustained delivery by using this technology while showing good local tolerability in the subcutaneous environment. The characterization of the depots at the end of the in vivo study suggests that the rapid phase exchange upon administration and the surface erosion of the resulting depots are driving the delivery kinetics from suspension formulations. Due to the widely accepted utilization of meloxicam as an analgesic drug for animal care, the results shown in this article are of special interest for the development of veterinary products aiming at a very long-term sustained delivery of this therapeutic molecule.

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NF-κB in Cancer Immunity: Friend or Foe?

Cells ◽

10.3390/cells10020355 ◽

2021 ◽

Vol 10 (2) ◽

pp. 355

Author(s):

Guilhem Lalle ◽

Julie Twardowski ◽

Yenkel Grinberg-Bleyer

Keyword(s):

Immune Responses ◽

Therapeutic Potential ◽

Cell Types ◽

Transcriptional Activators ◽

New Class ◽

Complex Interactions ◽

Cancer Immunity ◽

Distinct Cell ◽

Cancer Initiation ◽

Cancer Outcome

The emergence of immunotherapies has definitely proven the tight relationship between malignant and immune cells, its impact on cancer outcome and its therapeutic potential. In this context, it is undoubtedly critical to decipher the transcriptional regulation of these complex interactions. Following early observations demonstrating the roles of NF-κB in cancer initiation and progression, a series of studies converge to establish NF-κB as a master regulator of immune responses to cancer. Importantly, NF-κB is a family of transcriptional activators and repressors that can act at different stages of cancer immunity. In this review, we provide an overview of the selective cell-intrinsic contributions of NF-κB to the distinct cell types that compose the tumor immune environment. We also propose a new view of NF-κB targeting drugs as a new class of immunotherapies for cancer.

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Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders

Molecules ◽

10.3390/molecules26113389 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3389

Author(s):

Ishtiaq Ahmed ◽

Saif Ur Rehman ◽

Shiva Shahmohamadnejad ◽

Muhammad Anjum Zia ◽

Muhammad Ahmad ◽

...

Keyword(s):

Cannabinoid Receptors ◽

Cannabinoid Receptor ◽

Therapeutic Potential ◽

Endocannabinoid System ◽

Cell Types ◽

Autoimmune Disorders ◽

Specific Receptors ◽

Different Cell Types

In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer—both in vivo and in vitro clinical trials—has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.

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Bio-based polyurethane nanocomposite thin coatings from two comparable POSS with eight same vertex groups for controlled release urea

Scientific Reports ◽

10.1038/s41598-021-89254-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lixia Li ◽

Meng Wang ◽

Xiandong Wu ◽

Wenping Yi ◽

Qiang Xiao

Keyword(s):

In Situ Polymerization ◽

Polyhedral Oligomeric Silsesquioxanes ◽

Poly Ethylene Glycol ◽

Thin Coatings ◽

Polyurethane Coatings ◽

Coated Urea ◽

Poly Ethylene ◽

Coated Fertilizer ◽

Polyurethane Matrix

AbstractNanocomposite modification has attracted much attention in improving properties of bio-based polymer coating material for coated fertilizer. Herein two comparable polyhedral oligomeric silsesquioxanes (POSS), with eight poly(ethylene glycol) (PEG) and octaphenyl groups attached to the cage, respectively, were successfully incorporated into thin castor oil-based polyurethane coatings via in-situ polymerization on the urea surface. The nanostructure coatings are environmentally friendly, easy to prepare, and property-tunable. The results show that the vertex group of POSS had a pronounced influence on dispersion level and interaction between polyurethane and POSS that well-tuned the release pattern and period of coated urea, even at the coating rate as low as of 2 wt%. The liquid POSS with long and flexible PEG groups had better compatibility and dispersibility in polyurethane matrix than the solid POSS with rigid octaphenyl groups, as evidenced by SEM/EDS. The unique properties were resulted from the different extents of physical crosslinkings. This modification of bio-based polyurethane coating with POSS provided an alternative method of regulating and controlling the properties of coated fertilizer.

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Plasma membrane integrity in health and disease: significance and therapeutic potential

Cell Discovery ◽

10.1038/s41421-020-00233-2 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Catarina Dias ◽

Jesper Nylandsted

Keyword(s):

Plasma Membrane ◽

Therapeutic Potential ◽

Calcium Influx ◽

Membrane Integrity ◽

Cell Types ◽

Physical Parameters ◽

Membrane Repair ◽

Plasma Membrane Integrity ◽

Repair Mechanisms ◽

And Function

AbstractMaintenance of plasma membrane integrity is essential for normal cell viability and function. Thus, robust membrane repair mechanisms have evolved to counteract the eminent threat of a torn plasma membrane. Different repair mechanisms and the bio-physical parameters required for efficient repair are now emerging from different research groups. However, less is known about when these mechanisms come into play. This review focuses on the existence of membrane disruptions and repair mechanisms in both physiological and pathological conditions, and across multiple cell types, albeit to different degrees. Fundamentally, irrespective of the source of membrane disruption, aberrant calcium influx is the common stimulus that activates the membrane repair response. Inadequate repair responses can tip the balance between physiology and pathology, highlighting the significance of plasma membrane integrity. For example, an over-activated repair response can promote cancer invasion, while the inability to efficiently repair membrane can drive neurodegeneration and muscular dystrophies. The interdisciplinary view explored here emphasises the widespread potential of targeting plasma membrane repair mechanisms for therapeutic purposes.

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Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1

Nature Communications ◽

10.1038/s41467-021-22471-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Alexander Beatty ◽

Tanu Singh ◽

Yulia Y. Tyurina ◽

Vladimir A. Tyurin ◽

Svetlana Samovich ◽

...

Keyword(s):

Cell Death ◽

Therapeutic Potential ◽

Neutral Lipids ◽

Cell Types ◽

Lipid Hydroperoxides ◽

Conjugated Linolenic Acids ◽

Cellular Lipids ◽

Transcriptional Changes ◽

Acyl Chains ◽

Tumor Growth And Metastasis

AbstractFerroptosis is associated with lipid hydroperoxides generated by the oxidation of polyunsaturated acyl chains. Lipid hydroperoxides are reduced by glutathione peroxidase 4 (GPX4) and GPX4 inhibitors induce ferroptosis. However, the therapeutic potential of triggering ferroptosis in cancer cells with polyunsaturated fatty acids is unknown. Here, we identify conjugated linoleates including α-eleostearic acid (αESA) as ferroptosis inducers. αESA does not alter GPX4 activity but is incorporated into cellular lipids and promotes lipid peroxidation and cell death in diverse cancer cell types. αESA-triggered death is mediated by acyl-CoA synthetase long-chain isoform 1, which promotes αESA incorporation into neutral lipids including triacylglycerols. Interfering with triacylglycerol biosynthesis suppresses ferroptosis triggered by αESA but not by GPX4 inhibition. Oral administration of tung oil, naturally rich in αESA, to mice limits tumor growth and metastasis with transcriptional changes consistent with ferroptosis. Overall, these findings illuminate a potential approach to ferroptosis, complementary to GPX4 inhibition.

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Pituitary adenoma producing growth hormone and adrenocorticotropin: a histological, immunocytochemical, electron microscopic, and in situ hybridization study

Journal of Neurosurgery ◽

10.3171/jns.1998.88.6.1111 ◽

1998 ◽

Vol 88 (6) ◽

pp. 1111-1115 ◽

Cited By ~ 27

Author(s):

Kalman Kovacs ◽

Eva Horvath ◽

Lucia Stefaneanu ◽

Juan Bilbao ◽

William Singer ◽

...

Keyword(s):

Growth Hormone ◽

In Situ Hybridization ◽

Pituitary Adenoma ◽

Immunoelectron Microscopy ◽

Secretory Granules ◽

Cell Types ◽

Content Type ◽

Separate Cell ◽

Fine Print

✓ The authors report on the morphological features of a pituitary adenoma that produced growth hormone (GH) and adrenocorticotropic hormone (ACTH). This hormone combination produced by a single adenoma is extremely rare; a review of the available literature showed that only one previous case has been published. The tumor, which was removed from a 62-year-old man with acromegaly, was studied by histological and immunocytochemical analyses, transmission electron microscopy, immunoelectron microscopy, and in situ hybridization. When the authors used light microscopy, the tumor appeared to be a bimorphous mixed pituitary adenoma composed of two separate cell types: one cell population synthesized GH and the other ACTH. The cytogenesis of pituitary adenomas that produce more than one hormone is obscure. It may be that two separate cells—one somatotroph and one corticotroph—transformed into neoplastic cells, or that the adenoma arose in a common stem cell that differentiated into two separate cell types. In this case immunoelectron microscopy conclusively demonstrated ACTH in the secretory granules of several somatotrophs. This was associated with a change in the morphological characteristics of secretory granules. Thus it is possible that the tumor was originally a somatotropic adenoma that began to produce ACTH as a result of mutations that occurred during tumor progression.

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