College 2 – “Cells” – 29th of November
Cell Structure (important sites)
Ion will determine how a cell performs.
What happens outside the cell can influence the nucleus.
Cytoplasm (the cytoskeleton, ER and Golgi compelex is located in here)
Link the nucleus to the cell membrane
Nuclear envelope and nuclear pores
Chromatin (DNA and histones)
Endoplasmic Reticulum (smooth/rough)
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:
–Possess cell processes
–Synthesize non-rigid matrix
Small PGs, for example, decorin
–Capable of differentiating into several mature cell types
–Cell processes - cilia?
–Synthesise cartilage matrix
Collagen II, VI, IX, XI
Alkaline phosphatase (in calcified zone)
–Capable of undergoing hypertrophy during calcification process
–Capable of dedifferentiating to fibroblast morphology in culture conditions
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.
Capable of dividing
Synthesise bone matrix
- Collagen I
- 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
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
–On the same cell - autocrine
–Local - paracrine, synaptic
–Remote - endocrine
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.
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:
Tissue histogenesis - normal steady-state function of tissue
–cell production (skin, bone marrow), mass transfer (lungs, kidney),
–biochemical “refineries” (liver)
Tissue formation - the field of developmental biology
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.
Cells in tissues communicate with each other in 3 principal ways:
They secrete soluble signals, known as cytokines and chemokines e.g. growth factors
They make direct cell-cell contact
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
(two cell interacting with each other and the ECM)