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Related Concept Videos

Overview of Cell Death01:30

Overview of Cell Death

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Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
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Cellular Injury IlI: Cellular Death01:11

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Cell death is the irreversible loss of cellular structure and function, representing the final stage of severe injury. It plays a key role in both normal physiology and disease.Types of Cell DeathThe two main types are necrosis and apoptosis, though others like necroptosis and pyroptosis also exist.Necrosis:Necrosis is an unregulated form of cell death caused by severe injury such as trauma, toxins, or ischemia. It is characterized by cell swelling, membrane loss, rupture, and leakage of...
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Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

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Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
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Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
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Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
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The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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Polycation-mediated integrated cell death processes.

Ladan Parhamifar1, Helene Andersen2, Linping Wu1

  • 1Nanomedicine Research Group and Centre for Pharmaceutical Nanotechnology and Nanotoxicology, Department of Pharmacy, University of Copenhagen, Copenhagen Ø, Denmark; NanoScience Centre, University of Copenhagen, Copenhagen Ø, Denmark.

Advances in Genetics
|November 21, 2014
PubMed
Summary

Designing safe and effective nucleic acid delivery vehicles is crucial. Polyethylenimines (PEIs) are efficient but can cause cytotoxicity; understanding cell death pathways is key for developing safer transfectants.

Keywords:
ApoptosisAutophagyCell deathNanomedicineNecrosisPolycationsPolyethylenimine

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Area of Science:

  • Biomaterials Science
  • Molecular Biology
  • Cell Biology

Background:

  • Developing safe and efficient nucleic acid delivery vehicles is a significant challenge in gene therapy and molecular medicine.
  • Polycationic vectors, particularly native polyethylenimines (PEIs), are widely studied for their high transfection efficiency.
  • However, PEIs can exhibit cytotoxicity, with cell death mechanisms varying based on their architecture and molecular weight.

Purpose of the Study:

  • To review dynamic and integrated cell death processes relevant to polycationic vectors.
  • To discuss considerations for designing and interpreting cell death assays for evaluating PEI-based vectors.
  • To provide insights for developing safer and more effective nucleic acid delivery systems.

Main Methods:

  • Literature review of cell death pathways and assays.
  • Analysis of cytotoxicity mechanisms associated with polyethylenimines (PEIs).
  • Discussion of assay design principles for evaluating transfectant safety.

Main Results:

  • Cytotoxicity of PEIs is linked to diverse cell death pathways, influenced by vector properties.
  • Proper cell death assay design and interpretation are critical for accurate safety assessment.
  • Understanding these mechanisms aids in engineering improved PEI-based and other nucleic acid delivery vectors.

Conclusions:

  • Accurate assessment of cell death pathways is essential for the development of safe and effective nucleic acid delivery vehicles.
  • This review provides a framework for evaluating PEI cytotoxicity and designing safer transfectants.
  • The principles discussed are applicable to a broader range of gene delivery systems.