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Summary Tissue engineering and regenerative medicine
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- University Of Leeds (UoL)
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BLGY1211 Tissue engineering and regenerative medicineTissue engineering – the practice of combining scaffolds, cells, and biologically active
molecules into functional tissues. The use of a combination of cells, engineering materials,
and suitable biochemical factors to improve or replace biological functions
Regenerative medicine – refers to methods to replace or regenerate human cells, tissues
ore organs in order to restore or establish normal function. This includes cells therapies,
tissue engineering, gene therapy and biomedical engineering techniques, as well as more
traditional treatments involving pharmaceuticals, biologics and devices
Need for tissue engineering
The human body is subject to malfunction
Individuals can be born with congenital defects that affect organs or tissues
Diseases occur that lead to a destruction of an organ or tissue
Organs can be damaged due to accident or trauma
Clinical need has been identified for treatment of;
Congestive heart failure (5 million US patients)
Osteoporosis (10 million US patients)
Alzheimer’s and Parkinson’s disease (5.5 million patients each)
Severe burns (0.3 million)
Spinal cord injury (0.25 million)
Birth defects (0.15 million)
Diabetes mellitus (217 million patients worldwide)
Current approaches
Replacement with prosthetic devices
Transfer of tissue from one site to another
Transplantation of tissue or an organ form one individual to another
Organ transplant milestones
1954 – first kidney transplant USA
1962 – First living donor kidney transplant UK
1963 – First liver transplant USA
1965 – First kidney transplant in UK from cadaver
1967 – First heart transplant South Africa
1968 – First heart transplant UK
1968 – First liver transplant UK
1983 – First combined heart and lung transplant UK
1986 – First lung-only transplant UK
1994 – First living donor liver UK
1995 – First living donor lung UK
Living tissue donation
Kidneys, liver lobes and bone marrow can all be donated from a living person to a
patient
Usually a sibling or relative
, Antony Nolan trust created a register for people who are prepared to donate bone
marrow to a patient with blood cancer
Tissue transplants
Tissue donation coordinated by the NHS Blood and Transplant and Eye Services in
the UK
Most tissue are donated after death by patients who carry an organ donor card
Unlike organs tissues can be harvested from donors up to 24 hours after death
The following tissues are routinely banked for use in reconstructive surgery; cornea,
bone, heart valves, skin, tendons, amniotic membrane
Organ/Tissue transplant limitations
All grafts except cornea require long term immunosuppression
Immunosuppressive drugs have improved shot term survival
Long term survival (>5 years) has only improved slightly
Graft rejection is associated with cell-mediated responses to alloantigens (primarily
MHC molecules) expressed on the cells of the graft
Matching donor and recipient MHC improves the outcome of transplantation
Graft rejection still occurs due to imprecise MHC typing and differences in minor
histocompatibility antigens
Immunology
Innate immunity;
First line of defence – immediate
None specific; physical (skin, mucous, pH), cellular (macrophage, phagocyte),
physiological (temp, pH), inflammation (leakage of vascular fluid containing
phagocytic cells)
No memory
Adaptive immunity;
Longer response times
Specific to a given antigen
Diversity
Immunologic memory
Self/non self recognition
Response escalates with subsequent exposure
Cell mediated;
, Humeral (antibody);
Immunology of rejection
Most cells in the body have a marker known as Human Leukocyte Antigen (HLA)
If an organ is transplanted the HLA type might be different which triggers your
immune system which will attempt to destroy the organ/tissue
The donor tissue is tested to ensure that the HLA (tissue) types are as similar as
possible to reduce the reaction
Antibodies for HLA are also monitored to ensure the patient is not becoming
sensitized to the donor tissue
Rejection
Hyperacute graft rejection occurs with 24h of transplantation;
Pre-existing alloantibodies against specific antigens
Complement-dependent and occurs within minutes leading to infiltration of
neutrophils, resulting blood clots prevent vascularization
Recipient may have antibodies against donor graft antigens (previous
transplant or blood transfusion or even from pregnancy)
ABO matching important as well as tissue typing donor and recipient
Acute graft rejection occurs after from 1 week to 3 months;
Cell mediated response by macrophages and lymphocytes
Chronic rejection develops months or years after;
Both antibody and cell mediated response
Graft v host disease
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