SKIN GRAFTS FROM GENETICALLY MODIFIED PIGS MAY OFFER ALTERNATIVE FOR BURN TREATMENT
A specially-bred
strain of miniature swine lacking the molecule responsible for the rapid
rejection of pig-to-primate organ transplants may provide a new source of skin
grafts to treat seriously burned patients. A team of investigators from
Massachusetts General Hospital (MGH) report that skin grafts from pigs lacking
the Gal sugar molecule were as effective in covering burn-like injuries on the
backs of baboons as skin taken from other baboons, a finding that could double
the length of time burns can be protected while healing. The report in the
journal Transplantation has
been published online.
This exciting work
suggests that these GalT-knockout porcine skin grafts would be a useful
addition to the burn-management armamentarium," says Curtis Cetrulo, MD,
of the MGH Transplantation Biology Research Center (TBRC) and the Division of
Plastic and Reconstructive Surgery, corresponding author of the Transplantation paper. "We are actively exploring
options for establishing clinical-grade production of these grafts and hope to
begin a clinical trial in due course."
A key component in
the treatment of major burns, particularly those involving more than 30 percent
of the body surface, is removing the damaged skin and covering the injury,
preferably with a graft of a patient's own tissue. When insufficient undamaged
skin is available for grafting, tissue from deceased donors is used as a
temporary covering. But deceased-donor skin grafts are in short supply and
expensive -- disadvantages also applying to artificial skin grafts -- must be
carefully tested for pathogens and are eventually rejected by a patient's
immune system. Once a deceased-donor graft has been rejected, a patient's
immune system will reject any subsequent deceased-donor grafts almost
immediately.
The current study
was designed to investigate whether a resource already available at the MGH
might help expand options for protecting burned areas following removal of
damaged skin. For more than 30 years David H. Sachs, MD, founder and scientific
director of the TBRC, has been investigating ways to allow the human body to
accept organ and tissue transplants from animals. Sachs and his team developed
a strain of inbred miniature swine with organs that are close in size to those
of adult humans. Since pig organs implanted into primates are rapidly rejected
due to the presence of the Gal (alpha-1,3-galactose) molecule, Sachs and his
collaborators used the strain that he developed to generate miniature swine in
which both copies of the gene encoding GalT (galactosyltransferase), the enzyme
responsible for placing the Gal molecule on the cell surface, were knocked out.
When Cetrulo's team
used skin from these Gal-free pigs to provide grafts covering burn-like
injuries on the backs of baboons -- injuries made while the animals were under
anesthesia -- the grafts adhered and developed a vascular system within 4 days
of implantation. Signs of rejection began to appear on day 10, and rejection
was complete by day 12 -- a time frame similar to what is seen with
deceased-donor grafts and identical to that observed when the team used skin
grafts from other baboons. As with the use of second deceased-donor grafts to
treat burned patients, a second pig-to-baboon graft was rapidly rejected. But
if a pit-to baboon was followed by a graft using baboon skin, the second graft
adhered to the wound and remained in place for around 12 days before rejection.
The researchers also showed that acceptance of a second graft was similar no
matter whether a pig xenograft or a baboon skin graft was used first.
"These results
raise the possibility not only of providing an alternative to deceased-donor
skin for many patients but also that, in patients whose burns are particularly
extensive and require prolonged coverage, sequential use of GalT-knockout and
deceased-donor skin could provide extended, high-quality wound coverage,"
says co-author David Leonard, MBChB, of the TBRC and Division of Plastic and
Reconstructive Surgery. "A high-quality alternative to deceased-donor skin
that could be produced from a specially maintained, pathogen-free herd of GalT-knockout
miniature swine would be an important resource for burn management in both
civilian and military settings."
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