2 - Cell & Extracellular Matrix Flashcards
Three key elements for regenerative medicine
- Genes control the program of cell differentiation and proliferation
- Cells produce various matrix
- Matrix served as scaffold for cell growth/differentiation
Gastrulation
- Process of formation of intra embryonic mesoderm
- Starts at 14 days after fertilisation
Extra-cellular matrix
Cell derived ECM partially recapitulates the complete biological machinery of native tissue
Application of ECM
- Recreation of cellular niches
- Stem cell niche
- Tissue specific niches
- Engineering ECM in disease (e.g. tumour microenvironment)
- Engineering and characterisation of CD-ECM to student ECM Physiology
Embryonic ectoderm
Epidermis, nervous system, retina of the eye, etc
Embryonic endoderm
Endothelial linings
Embryonic mesoderm
- Smooth muscular coats
- Connective tissues
- Vessels
- Cardiovascular system
- Blood
- Bone marrow
- Reproductive and excretory organs.
Organ-genetic period of embryonic development
- 3rd week (5 weeks after the first day of last normal menstrual period)
- 4 phases : growth, morphogenesis, differentiation, maturation.
Morphogenesis
Complex interaction occurring in an order sequence, cell movement and cell transformation (EMT, MET) and program cell death.
Development of skin
- 4 to 5 weeks
- Epidermis (Derived from surface ectoderm)
- Dermis (derived from mesoderm)
Development of cartilage after 5 weeks
Paraxial mesoderm –> Somites –> Condensation of mesenchymal cells –> Chondrification centres –> chondroblasts
Three types of chondroblasts
- Hyaline
- Fibro
- Elastic
Development of bone
Membrane sheath –> Condensation of mesenchymal cells –> Vascularisation –> Osteoid matrix deposition
Development of skeletal muscle
- Seven weeks
- Myotome regions of the somites (mesoderm)
- Mesenchymal cells
Developmental of smooth muscle
- Somatic mesoderm (vessels smooth muscle)
- Mesenchymal cells (myoepithelial cells in glands)
- Splanchnic mesenchyme (around endoderm, other smooth muscle)
- Remain mononuclear
Development of cardiac muscle
- 4 weeks
- Lateral splanchnic mesoderm
- Cardiac muscle fibers arise form single cells
Development of PNS
- Neural crest cells
- Cranial, spinal visceral nerves and cranial, spinal and autonomic ganglia
- Bipolar of sensory cells
- Satellite cells
- Schwann cells
- Connective tissue outside the capsule.
Stem cell niche
Refers to a microenvironment, within the
specific anatomic location where stem cells are found, which interacts with stem cells to regulate cell fate.
Epithelial mesenchymal transformation (EMT)
- process by which epithelial cells lose their cell polarity and cell–cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells
- Neural crest
- Cardiac cushion cells
- Midline cells of the palate
- Dermis of the skin
- Limb musculature
- Sclerofome
Mesenchymal Epithelial transformation (MET)
- Kidney tubules
- Nephrogenic blastema
- Endocardium
- Somities
Matrix proteins
- Fibrous structural proteins
- Specialised proteins
- Proteoglycans
- Matrix degrading enzymes
Fibrous structural proteins
Collagen, laminis, fibronectin, vitronectin and elastin.
Specialised proteins
Growth factors, small matricellular proteins, small integrin binding glycoproteins
Matrix degrading enzymes
MMP, serine protease, cysterine protease
5 pathways that determine cell transformation
- Growth factors
- TGF beta
- B - catenin
- Integrins
- Inflammation / NFkB
Cell - ECM interactions
Integrins and receptors
Cell - Cell interactions
Eph/ephrin family
What is tissue morphogenesis dependent on
Changes in either cell shape or oriented cell division and relies on cells exchanging their neighbours
Essential components for engineering of regenerative medicine
Gene, Cell and Matrix
Function of Bone morphogenetic proteins (BMPs)
- Binds to heparitin sulfate, heparin, type IV Collagen
- Regulates maturation, differentiation, ECM production
Functions of cadherin
Mediate homophilic interaction during EMT/MET
Three types of cadherin
- N-Cadherin
- E-Cadherin
- Cadherin’s partner
N-Cadherin
- Ill-formed somites
- Abnormal neural tubes
- Loosely organised myocardium
- No EMT
E-Cadherin
- MET
- Trophectoderm fail to form
Cadherins partner
Catenins (αβ) via phosphorylation
Integrins as ECM receptors
Heterodimeric trans membrane protein αβ subunits.
