Yesterday, we talked about Ali-BAL– the bioreactor that can (possibly) afford folks the ability to recover from liver poisoning.  After all, we know that livers are not readily available for transplantation- and engineering a liver is rather difficult because of the blood vessel networks that are incorporated in the liver.

Today, we are going to consider an out-of-the-box idea about livers.  Then, I’ll explain a few of the issues with the concept.

Lei Dong (and a bunch of compatriots across China) considered the fact that our bodies really can survive without having a functioning spleen.  So…

The concept was to remodel an existing organ to take over the function of another- one that is diseased or dysfunctional.  The remodeled organ would already have the vasculature the body needs- and could be a vessel for the new cells that need to function.

Lei Dong’s team centered their plan about the spleen.  After all, it’s a large, peripheral lymphoid organ; no, it’s really a vestigial hematopoietic organ. And, any functionality the spleen provides can be replaced by the lymph nodes (lymphoid function) or the kidney (blood filtration).  Moreover, the spleen is pretty big with a great blood supply from the hepatic artery.  If the spleen is converted, there won’t be any rejection syndrome or the needs for anti-rejection drugs.

The team- Drs.  Lintao Wang, Zhenzhen Wang, Jingjing Gan, Chunuan Liu, Dianhua Chen, Junfeng Zhang, and Lei Dong  (all of Nanjing University);  Chunming Wang and Yiming Niu  (University of Macau); and Suhua Xia (The First Affiliated Hospital of Soochow University, Suzhou)  published their creative research in Science Advances (Transforming the spleen into a liver-like organ in vivo).

They had a few hurdles to surpass to bring this idea to test.  They needed to make the spleens bigger and stiffer- so that they could withstand the growth (after injection) of the liver cells.  The researchers did this remodeling by injecting a tumor extract (actually the supernatant of the tumor– solute tumor homogenate [STH]).  This afforded growth of epithelia, making the spleen larger.  Of course, the concept would only work if the remodeled spleens could integrate with the blood vessels- and act as liver tissue.  The liver tissue employed was transplanted allo-, auto- and xenograft liver cells; injected directly into the spleen.    And, over 8 weeks, the researchers found their idea had merit.  (The ‘livers’ actually produced bile ducts and other liver structures.  And, they effected essential liver functions- including drug metabolism.)

Then, came the acid test.  (OK, they really didn’t use acid!).  But, the researchers did remove 90% of the mice livers to determine if the ‘sp-livers’ could pick up the slack.  All of the mice with ‘sp-livers’ survived; none of the mice who had regular spleens and only 10% of their livers did.

However… the sp-liver has vastly different blood supply from the actual liver.  And, the liver obtains intestine-derived growth factors and other nutrients from portal blood.   The spleen has no such access.

The sp-liver has no access to the portal vein, so detoxifying portal vein blood is out of the question.

And, if these weren’t impediments enough- most folks with liver disease also have damaged spleens.  Which means converting them to sp-livers may be problematic.

But, the concept (which existing organ can be modified) could be altered.  Consider what Dr. Eric Lagasse (University of Pittsburgh) has planned.  (He’s already tested this in animals.)  His group is growing liver-type organs in the lymph nodes- and the lymph supports new tissue growth and has more connections than the spleen.  Lagasse is about to try this out in humans!

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