Honors Biology 298 - Week 15
tissue engineering
this field focuses on the developments of substitutes for damaged tissues and organs
millions of people lose the function of tissues and organs and then must resort to mechanical devices (dialysis machines, pacemakers), organ transplants or reconstructive surgeries to maintain their health
costs of treating such patients is estimated at $400 billion a year and more than 8 million surgical procedures
the scarcity of organs and organ donors is a serious problem and most transplant patients die while waiting for a suitable organ
tissue engineering provides a viable alternative whereby the principles of engineering and biology are combined
take isolated cells from someone, change them and let them grow and re-form the
correct tissue when the appropriate conditions are provided
sometimes a synthetic polymer is needed to serve as a substrate for cells to help
induce the formation of functional and morphologically correct tissues
polymers can be biodegradable and break down over time or they are
non-degradable and remain in the patient permanently
a variety of tissues including the nervous system, skin, cornea of the eye, liver,
pancreas, bones and cartilage, muscles and blood vessels are being tested
liver – hepatocyte transplantation
replace “bad” liver cells (hepatocytes) with hepatocytes that are grown on a
polymer so they remain active and differentiated and then are transplanted
actually place hepatocytes in a hydrogel microcapsule
why use a capsule?
pancreas – transplantation of encapsulated functional pancreatic cells that produce insulin
semiporous microspheres protect insulin-producing cells
skin – required after a severe burn and other skin injuries
add a certain type of polymer (collagen: most abundant protein in body, structural
protein found in skin, bone, cartilage, muscle)
on top of the collagen, add epidermal cells (skin cells) from the patient
research with embryonic stem (ES) cells (pluripotent) and being able to grow them
take human embryo and let it develop to 16-cell stage and then remove ES cells
any ethical problems with this?
what about using cow eggs and nuclear transfer of a human cell (fibroblast)
nucleus
early payoff might be production of nerve or heart cells for transplant
and ultimately organs
private funding, not federally funded reaction
if tissue can’t be engineered, then do organ transplantation
the success of organ transplantation and skin grafts depends on matching histocompatability antigens
in humans, antigens produced by a cluster of genes on chromosome 6 known as
the HLA complex (human leukocyte antigen complex)
the HLA complex consists of 4 neighboring genes: HLA-A, HLA-B, HLA-C,
HLA-D
however, problems arise because a large number of alleles have been identified
for each of the HLA genes, making it possible to have literally millions of allele
combinations
the array of HLA alleles on a given copy of chromosome 6 is called a haplotype
since we carry 2 copies of chromosome 6, then we each have 2 HLA haplotypes
very rare that anyone will be genetically identical to someone else
successful transplantation of organs and tissues depends upon matching HLA haplotypes between donors and recipients
identical twins>sibling>parent>unrelated donor
chances for an unrelated match is
difficult to match across racial and ethnic lines
when HLA types are matched, the survival of transplanted organs is dramatically improved
ex: after 4 yrs, matched has a 90% survival rate whereas unmatched has <25%
even when well matched, patients still have to take immunosuppressive drugs
how many transplants? which organs? how many others on a waiting list?
the problem is that over 3000 people on a waiting list die each year and another 100,000
die before they even get put on the list
problem of supply and demand….
how might we get around this?
financial incentives?
people on waiting list have a relative that is not a match, but agree to donate
an organ
could xenotransplantation be the answer?
what animals used? what is the rate of success?
probably will focus on pigs because of size and the physiological similarities to humans
what other problems?
transmission of infectious diseases
expose humans to nonhuman viruses
ex: primate viruses actively attack human cells and kill them
not many researchers want to perform primate-to-human transplants these days
ex: pig viruses also have been found to infect human cells
swine flu and other more deadly strains of influenza, other unknown viruses?
immunological problems
the cell surface proteins (part of the HLA system) that act as antigens are very different
animal organs have very different surface proteins that will trigger an immediate and massive response from immune system
how could this be avoided?
isolate and clone human genes that shield or protect organs from attack
if genes encoding these proteins can be successfully transferred to donor animals (inject transgenes into fertilized eggs), their organs will express human recognition proteins
waiting for the first transgenic animal-to-human transplant
does xenotransplantation place public health at risk and is this an unacceptable technology?
should there be an indefinite freeze on all forms of experimentation and clinical application of this technology?
once again, much of this work has been done in private industry
estimates of 100,000 transgenic pigs on an annual basis, which potentially translates into a mutli-billion dollar industry
is big business now the driving force behind xenotransplantation?
do dollar signs outweigh the public good?