Summary Tissue engineering and regenerative medicine

BLGY1211 Tissue engineering and regenerative medicine

Tissue 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