Regenerative Medicine Flashcards
What is tissue regeneration?
Regrowth of damaged tissue
What organs can regenerate in a human adult?
Liver, skin
What tissue is in particularly gooNextd at regeneration and what tissues have no regenerative capacity at all?
Epithelial is good at regeneration, whereas cartilage and nerve tissue have no regenerative capabilities
What is tissue engineering?
Practise of combining scaffold with cells and essential molecules for ECM formation into functional tissues
What can tissue engineering be used for?
Structural replacement, functional replacement (musculoskeletal) and wound healing
What kind of cell is the best cell for engineering cartilage?
Chondrocytes
What is regenerative medicine?
Includes tissue engineering and self-healing, and the use of foreign materials to rebuild tissues and organs
What are the key ingredients for tissue engineering? (5 marks)
Cells for the ECM
Xenogenetic cells
Sourcing cells from different biopsies e.g. bone marrow and placenta
Source cells from native tissue Bioactive molecules
What are scaffolds?
Natural products used to support new tissue. Made of protein/ polysaccharides derived from animals
What do the cells used to make up the ECM need to do?
Can synthesise and release bio-active molecules and they need to be able to reflect the nature of the cell tissue
What are xenogenetic cells?
Cells derived from different species
How can we use mesenchymal stem cells for tissue engineering?
Use them and Sox9 to push the cells down to differentiate into chondrocytes
What are the bioactive molecules used for tissue engineering and what are they used to maintain?
Growth factors, interleukins, anti-inflammatory molecules. They are used to maintain cells metabolism
What are vegetative sources that you could use for ECM?
Collagen fibres
What is the benefit to using fibrin/ collagen fibres?
They are more compatible and biodegradable
What are 2 beneficial characteristics of collagen?
High mechanical strength and low antigenicity
What is low antigenicity?
Something that won’t elicit an immune response
What does fibronectin do? What is this a result of?
Promotes cell adhesion through integrin surface of the cell this is due to motif RDG AA which attracts cell adhesion through integrins on the surface on plasma membranes
What is a benefit to using a natural product?
More biocompatible and biodegradable has inherent mechanical and biological properties consistent with in vivo features of a tissue
What is a benefit of using synthetic bio materials?
Can be moulded into variety of shapes and sizes
What can an ACL injury lead to?
Early onset arthritis or osteochondrosis dissecans
What is osteochondrosis dissecans?
Inflammation of bone and cartilage resulting in formation of loose fragments
What is OCD characterised by?
Spontaneous avascular necrosis, inflammation, genetic predisposition and repetitive microtrauma
What is OCDs pathophysiology?
Idiopathic focal joint disorder affecting subchondral bone
How does OCD occur?
- First get fragment of cartilage and subchondral bone that separate from articular surface.
- Secondly, you have early changes in subchondral underlying bone which will receive a low blood supply = osteonecrosis
- Then bone fragment loosens until it loosens the cartilage (decalcification) and if the cartilage is ruptured on 2 sides get displacement of cartilage and bone
What can an untreated loose fragment of OCD lead to?
Degenerative arthritis
What is the process of tissue engineering autologous chondrocyte transplantation?
(6 marks)
=> Cartilage harvested from low weight bearing region (upper medial femoral condyle)
=>Cartilage digested
=>Cells seeded into tissue culture flasks at cell density of 5000-10000 cells per cm2 and maintained in autologous serum
=> Transplantation then 12-14 days after initial surgery chondrocyte trypsin treated and washed and resuspended in 500-1000ul vol of 2.5-2.6 mill cells
=>Chondral lesion excised to surrounding normal tissue. Cartilage defect covered w/ periosteal flap and sutured to normal cartilage, periosteal flap potential source of growth factors ad stem cells
=>Autologous chondrocytes injected between periosteal flap to initiate repair and remodelling of cartilage ECM
What were the results found in the transplantation chondrocyte experiment?
Knee locking was eliminated as well as reduced pain and swelling. Transplant tissue was spongy w/ some level of integration surrounding normal tissue
Recap the stages of 1st generation ACL repair (chondrocyte transplantation).
- Cell precursors - autologous chondrocytes from healthy cartilage
- Natural product - periosteum - source of stem cells and growth factors to maintain cell phenotype and promote to cover defects
- Sutures - sealing periosteal flap
- Modification of procedure use fibronectin and thrombin autologous to seal periosteal piece over defect
What cell precursors (CP) and scaffolds are used in different generations of ACL under the autologous matrix induced chondrogenesis?
1st gen ACL: CP - autologous chondrocytes scaffold - one but use of periosteal flap and collagen membrane
2nd gen: CP - autologous chondrocytes scaffold - hydrogels, fibrous scaffold, decellularized ECM
3rd gen: CP - allogenic stem cells, autologous stem cells scaffold - hydrogel, fibrous scaffold, decellularized ECM for composite
What is easier to produce and use in ACL repair that doesn’t involve removing the periosteal flap?
Using replacement bio material
Why are mesenchymal cells being considered for stem cell therapy in osteoarthritis?
Due to their ability to sourced from many or all joint tissues. Also able to undergo several rounds of cell division prior to differentiation into range of mesenchymal cell types
