Flashcards in BMS354 Principles of Regenerative Medicine and Tissue Engineering Deck (407)
What is the difference between regenerative medicine and tissue engineering?
- Regenerative medicine is an umbrella term that includes tissue engineering and cell therapy.
- Tissue engineering differs from cell therapy through the use of biomaterials. Biomaterial can be used in both but in tissue engineering it is used more as a scaffold
- Tissue engineering also has some applications that are distinct from regenerative medicine. For example, lab grown food
Wy is there a clinical need for tissue engineering?
Organ failure is one of the most costly challenges faced in healthcare and the current treatments have many limitations
What are the available treatments for organ failure?
- Pace maker
- Hip replacements
- Skin grafts
- Organs from donors
What are the limitations of surgical reconstruction as a treatment for organ failure?
Morbidity at the donor sites
What are the limitations of mechanical devises as a treatment for organ failure?
- Only mechanical support
- Do not grow with the tissue – children with these will need multiple surgeries to replace as they grow
What are the limitations of transplantation as a treatment for organ failure?
- Must be on immunosuppressors
- Supply and demand – due to the limited supply, doctors are forced to use organs that may not be ideal e.g. from an elderly person
- E.g. in 2014, two patients who had a kidney transplant died sue to the kidney being infected with a parasitic worm
When did the tissue engineering field emerge?
- This research emerged in the 1970s and 1980s and was coined Tissue engineering in 1987
- In the 1990s research accelerates and industry begins to emerge - In 1998, human embryonic stem cells were isolated
What are the building blocks of tissue engineering?
Biomaterial scaffold (provide physical support)
Bioactive molecules (direct cellular behaviour)
Regenerative medicine and tissue engineering are multidisciplinary research fields. What other disciplines participate?
- Material science
- Cell, physiology, anatomy, molecular, computational biology
What tissues form an organ?
Epithelial, connective, muscle and nerve tissue form an organ
What is the role of the different tissues that make up an organ?
Epithelial tissue carry out the function while muscle and connective tissue provides structure
What are the three stages of wound healing?
Explain the inflammatory phase of wound healing
- Clears out dead cells from the injury and limiting the extent of tissue damage to prepare the environment for healing
- Arterioles and venules near the site of injury constrict briefly and then dilate. This increases capillary permeability which moves fluid into the effected tissue. Blood clots occur due to increased blood viscosity
- Leukocytes engulf bacteria and cellular debris through phagocytosis to clean the wound and secrete growth factors which recruits fibroblasts
Explain the proliferative phase of wound healing
- New tissue formation occurs to fill the wound space
- Fibroblasts secrete collagen and growth factors which promote angiogenesis and endothelial cell proliferation and migration.
- Granulation tissue is formed by fibroblasts and endothelial cells. It forms 2-4 days post the wound. Microscopically looks very granular due to newly formed blood vessels and forms the scaffold for remodelling
- The newly formed blood vessels are leaky and allow blood cells and plasma cells to leak into the tissues
- Epithelisation – when there is proliferation and migration of epithelial cells to form the new surface
Explain the remodelling phase of wound healing
- Begins after three weeks
- Remodels the new connective tissue. This can take months and sometimes years
- Final scar tissue formed by collagen synthesis and becomes avascular
- Scar tissue can achieve 70-80% tensile strength by the end of three months
What is the difference between regeneration and repair?
- If the injury is only mild and superficial then the epithelium will be regenerated and there will be no scar
- If the injury is severe then a scar will form
What decides whether an injury will result in regeneration or repair?
The outcome of the injury is dependent on the severity, tissue damaged and length of injury
What is fibrosis and how is it different to repair?
Persistent tissue damage that results in a tissue scar
The process of scar formation is the same as repair but this term refers to when a stimulus is persistent
Give an example of fibrosis
What is meant by Fibrous encapsulation?
The body will try to protect itself from biomaterials by producing lots of collagen leading to its isolation from the bodies environment
What cell sources are used in regenerative medicine?
]Autologous: From same person
Allogenic: Same species but different people
Xenogeneic: Different species
Syngeinc or isogenic: Genetically identical but different person (twins)
What different cell types can be used in regenerative medicine?
Differentiated mature cells
Mixture of differentiated cells
What are the advantages and disadvantages of using differentiated mature cells in regenerative medicine?
- These cells cannot self-renew meaning they can’t expand into large numbers
- However, these cells are already functional. This is an advantage over stem cells as differentiation of stem cells is sometimes difficult to get mature functional stem cell
What kind of differentiated mature cells are used in regenerative medicine?
Fibroblasts, keratinocytes, osteoblasts, endothelial cells, chondrocytes ect.
What kind of stem cells are used in regenerative medicine?
Adult stem cells
- Can be taken from the patient so will be no immune response
- If person has genetic disease this doesn’t help
Embryonic stem cells
- Can differentiate into any cell type
Induced pluripotent stem cells
- Can still be taken from the same person –allogenic
- Can differentiate into any cell type
How are cells cultured in a lab?
- Cells are cultured in growth medium which contains the necessary requirements for cell growth e.g. nutrients, growth factors
- Laminar hood keeps aseptic
- Incubated at 37 degrees
- Lids of the petri dish are not sealed as there needs to be gaseous exchange
What ensures that the cells cultured for patient use are of a good quality?
Good manufacturing practice (GMP) ensures that medicinal products are consistently produced and controlled to the quality standards appropriate to their intended use
Must be free from animal products
What is the role of the ECM?
ECM provides support for cells and contributes to the mechanical properties of the cells. It also provides bioactive cues for cells, acts as the reservoirs of growth factors and potentiates their actions and acts as a scaffold for orderly tissue renewal
What is the composition of ECM?
Fibrous structural proteins – Collagen, elastins
Water hydrated gels – proteoglycans, hyaluronan
Adhesive glycoproteins – fibronectin, laminin