Partial Liver Transplantation
Massive hepatic resection is the only option for some patients with primary or secondary liver tumors. With regard to small-for-size (SFS) liver transplantation, the use of partial liver grafts has the potential to substantially reduce the donor shortage by allowing the donor organ to be split between 2 recipients.
Xenotransplantation
Due to the shortage of available human organs the pig has been chosesn as a source for xenotransplantation organs. The first major hurdle in carrying out a cross species xenotransplantation is the occurance of hyperacute rejection triggers by complement activation. (Knoell, EP1336618).
Risk associated with Liver Transplantation
Liver resection has bewcome an increasinly safe procedure, but certain procedures remain high risk, such as massive liver resection and small-for-size (SFS) liver transplantation.
Ischaemic-reperfusion injury (IRI):
IRI is an inevitable phenomenon that results following major liver surgery, including partial hepatecotomy and liver transplantation (Gomez, World J Gastroenterol 2007, February 7: 13(5): 657-670).
Tang teaches that partial grafts form split livers have been introduced to expand the donor pool, briding the gap between the increasing number of potential recipients and the inferior number of eligible liver donors but that there are mroe risks in performing partial or small for size liver transplantation, not only due to technical obstances, but also early graft loss resulting from ischemia reperfusion injury (Tan, Transplantation Proceedings, 39, 1338-1344 (2007)).
–Mechanisms:
(i) complement system: Studies using rat models indicate a central role for complement in hepatic IRI. However, in addition to its role in hepatic IRI, evidence indicates that complement activation is required for normal liver regeneration, following either resection or toxic injury. Data indicates that the complement activaiton products C3a and C5a play an important role in the proliferative response and hepatocyte regeneration via an effect on TNF alpha and IL-6 expression. (he, J. Clinical Investigation, 119(8), 2009).
Alternatives to Liver Transplantation: Regenerative Medicine
In the treatment of liver failure, transplantation of hepatocytes into ectopic sites, including the spleen, pancreas, peritoneal cavity, and subrental capsure has been proposed. Feasibility and efficiacy of these techniques have been confirmed in preclinical studies, but clinical success rates have been limited thus far and new methds are needed to improve heaptocyte engraftment. (Komori, “The mouse lymph node as an ectopic transplantation site for multiple tissues” Nat Biotechnol. 2012, October, 30(1); 976-983).
Lymph Nodes as Bioreactors:
A novel approach to treating end-stage liver disease involves using a patient’s own lymph nodes as a “bioreactor” to grow functional liver tissue. This method, developed by LyGenesis, involves injecting donor liver cells into a lymph node, where they are able to proliferate and form a new, functional liver structure that can compensate for a failing or diseased liver.
There are over 500 LNs in the human body, many of which are relatively easily accessible. While a single LN structurally limits the number of donor cells that can be transplanted, it is technically feasible to transplant more than one LN in order to gain sufficient organ/tissue function from the transplanted cells. The potential loss of function in a few LNs does not appear to compromise the overall funciton of the lymphatic system. In fact, lymphedema is the most common complication following lymphadenectomy in patients with cancer and only affects a limited number of patients. (Komori, “The mouse lymph node as an ectopic transplantation site for multiple tissues” Nat Biotechnol. 2012, October, 30(1); 976-983).
By directly injecting the LN with hepatocytes, thymuses, or pancreatic islets, demonstrate engraftemtn of the donor cells and subsequent organ funciton. This new approach of using the LN as an in vivo bioreactor in which to regenerate functional organs may be beneficial to the field of regenerative medicine. (Komori, “The mouse lymph node as an ectopic transplantation site for multiple tissues” Nat Biotechnol. 2012, October, 30(1); 976-983).