Organ Transplants

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Life is tough if you are waiting for a transplant organ.  Whether it’s a kidney, a lung, or a heart.

One of the biggest issue- besides the general lack of availability- is the need for blood match.  No match and our immune system will destroy the newly transplanted organ.  Within days.

It’s hard to believe that this action is triggered by sugars (actually called antigens) on the surfaces of the organs, blood cells, and blood vessels.  These antigens stimulate an immune response  (activated lymphocytes or white blood cells that fight infection).

So, the technique pioneered by Dr. Marcelo Cypel (University Health Network Transplant Program in Toronto) is a pretty novel and radical idea.

Type A antigen stripping

Cypel uses an enzyme concoction to remove those antigens- in this case on the surfaces of lungs that come from folks with type A blood.  Once those antigens are stripped away, the organ is theoretically now a type O lung.  And, type O is the universal blood donor type.  That means instead of a potential 55% pool of donors, the enzymatic conversion process means that in excess of 80% of the lungs can be used for transplant.  (OK, not quite- but more about that later.)

These initial results are reported in Science Translational Medicine, “Ex vivo enzymatic treatment converts blood type A donor lungs into universal blood type lungs”.

Dr. Cypel, along with 22 others were the authors of the study.  One of the key additions to the team was Dr. Stephen Withers (U British Columbia);(I reported his finding here) his critical contribution was his finding (along with his postdoc, Dr. P Rahfield) that gut microbes have two enzymes that literally swipe away the Type A antigens from red blood cells.  (This study is the first proof that said enzymes can do the same for whole organs, not just red blood cells.)

To effect such a conversion on an entire organ, the lung was placed in a temperature controlled dome, connected to a ventilator (like employed on patients in ICU’s).  Perfusion of the lung was effected with a solution of nutrients and proteins- and the critical enzymes to strip out the antigens-  to sustain cellular perfusion.  The ex-vivo (outside of life) perfusion was found to be effective after four hours; some 97% of the antigens were stripped away during this time period.

Ex Vivo Lung Perfusion

Except that was just a preliminary step.  The researchers still had to determine if the lungs would be suitable for transplantation; in other words, that the patient’s immune system would not attack the lung tissues.  It would not surprise a soul that a lung that did not have the enzymes added to the perfusion concoction were readily attacked by the immune system; eventually, an inordinate amount of pressure was required to get air pumped through those lungs.

The 97% cleared lungs (i.e., those that underwent this novel treatment) escaped immunity attacks.  No additional inflammatory compounds were detected and the lung function was stable.

But, knowing that antigens grow back means these lungs may not still be suitable for transplantation.  Given that the first three days are the critical period to discern organ acceptability,  the researchers hope that immune suppression techniques may let the lung continue to function long term.

There’s still another wrinkle.  Animal testing is problematic, since their blood types differ from humans.   So, the researchers are going to genetically modify mice to have human blood types- as well as test the lungs on pigs (which do have Type A antigens).   This will allow for clinical trials within the next year or so, using humans with relatively few Type A antigens.

Obviously, if that works, then other organs can be tested.   There already are ex-vivo perfusion devices for kidneys, livers, and hearts.  So, if the concept works for lungs, it should work for these organs.

Maybe those long transplant lists can finally wither away.

 

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4 thoughts on “Organ Transplants”

  1. That would be so wonderful. I lost a friend about 12 years ago who needed an organ transplant and was on a list when she died, and one of my relatives lost her husband to the same need (this about 30 years ago).

  2. This would be terrific if it works long term. My granddaughter has O type blood and has signed up to be an organ donor.

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