College 1 – “An introduction to Tissue Engineering” – 22nd of November 2012



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College 2 – “Cells” – 29th of November


Cell Structure (important sites)

  1. Plasma membrane

    1. Ion channels
       Ion will determine how a cell performs.

    2. Transmembrane proteins

    3. Receptor molecules

    4. Microvilli

  • What happens outside the cell can influence the nucleus.

  1. Mitochondrion
    Cytoplasm (the cytoskeleton, ER and Golgi compelex is located in here)



  2. Cytoskeleton

    1. Microtubuli

    2. Intermediate filaments

    3. Actin filaments

Link the nucleus to the cell membrane

  1. Nucleus

    1. Nuclear envelope and nuclear pores

    2. Chromatin (DNA and histones)

  2. Endoplasmic Reticulum (smooth/rough)
     Protein synthesis

  3. Golgi complex

    1. Secretory vesicles

    2. Lysosomes

  • Often the protein production is studied with molecular biology but also the analysis of protein in ECM is important.

  • Proteins etc. are transported in and out the cell with exocytose and endocytose.

Sorts of cells:

  • Fibroblast

  • Flattened/elongated morphology

–Divides extensively

–Possess cell processes



–Synthesize non-rigid matrix

  • Collagen

  • Versican

  • Small PGs, for example, decorin

–Capable of differentiating into several mature cell types

–Cell processes - cilia?
–Synthesise cartilage matrix

    • Collagen II, VI, IX, XI

    • Aggrecan

    • Hyaluronan

    • Alkaline phosphatase (in calcified zone)
      –Capable of undergoing hypertrophy during calcification process
      –Capable of dedifferentiating to fibroblast morphology in culture conditions

    • Avascular tissue
       so cannot use oxygen for energy, it uses glucose instead

    • In monolayer chondrocyte will become a fibroblast, you can tell from the type of collagen that is produced by the cell.

  • Osteoblast

    • Cuboid morphology

    • Capable of dividing

    • Synthesise bone matrix
      - Collagen I
      - Osteonectin
      - Osteocalcin
      - Hydroxyapatite
      - PG
      - Alkaline phosphatase
       these are all bonemarkers

    • Differentiate into osteocytes, which are embedded in matrix (mechanical load sensor).


Extracellar Signalling Molecules

  • Hormones - Insulin, human growth factor

  • Growth factors - FGF, PDGF
     Different growth factors have a role in different cells.
     Specific growth factors are only needed to stimulate certain processes instead of the whole coctail

  • Cytokines - Interleukin -1b

  • Neurotransmitters

  • Prostaglandins - PGE1, PGE 2/3

  • All are relatively small molecules <50kD

  • Hydrophilic - bind to cell surface receptors e.g. FGF
    Hydrophobic - diffuse through the plasma membrane and bind to receptors inside the target cell e.g. steroids

  • Cellular fate processes that underlie the dynamic states of tissue function
    –Cell division - an increase in cell number
    –Cell differentiation - changes in gene expression and the acquisition of a particular function
    –Cell migration - motion of a cell into a specific niche or location
    –Cell apoptosis - programmed death of cell
    –Cell adhesion - physical binding of cell to its immediate environment i.e. neighbouring cell, ECM or artificial surface

  • Effects
    –On the same cell - autocrine
    –Local - paracrine, synaptic
    –Remote - endocrine


Cell therapy

  • First there was transfusion of cells. The first cells to be donated were blood, after that whole organs were transplanted. The first kidney to be transfused successful was in 1962, than more organs and cells succeeded.

  • How many cells do you need for a working organ?
    The body has 1014 cells, an organ 109-1011

  • The fundamental limitations to the production of primary cells number of cell divisions in culture 30-50 doublings depending on age of cell, in theory, >1010 cells not all cells grow easily in culture e.g. liver and b-islet cells.

  • How rapidly do primary cells grow in culture ?
    Dermal foreskin fibroblasts (HUFFs) exhibit doubling times of 15 h, adult chondrocytes exhibit doubling times of 24-48 h.
     Depends on the activity of the cell.

  • How are these cells currently produced ?
    Fairly primitive i.e bags, T flasks and bioreactors.


Tissue Dynamics

Tissues are composed of many cell types of various developmental origins . The dynamic behaviour of cells and their interactions determine overall tissue formation, state and function. The three dynamic states of tissue are:



  1. Tissue histogenesis - normal steady-state function of tissue
    –cell production (skin, bone marrow), mass transfer (lungs, kidney),

–biochemical “refineries” (liver)

  1. Tissue formation - the field of developmental biology

  2. Tissue repair - biopsied tissue displays a healing type response in culture

  • These thing change all the time.

  • The time to make enough cells for one organ varies a lot.


Communication

Cells in tissues communicate with each other in 3 principal ways:



  1. They secrete soluble signals, known as cytokines and chemokines e.g. growth factors

  2. They make direct cell-cell contact

  3. They make proteins that alter the chemical microenvironment (ECM) On the cell surface there are adhesion and ECM receptor molecules

Each communication differ in terms of

–characteristic time and length scales



–their specificity


(two cell interacting with each other and the ECM)

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