Liver stem cells as they relate to regeneration

[merryBe]

For both HCV disease, and for transplant patients the question of liver regeneration becomes an important one.

Especially for those who are given a live donor transplant, where they will still have to regrow 2/3 of a liver (and do grow it back in a year or so's time) the question of how liver cells grow and divide, and how to stimulate the body's own stem cells becomes as important topic.

Evidently, the greater the injury, the greater the chance of stem cells coming to the rescue.
Although research into growing stems for individual patients is a long way off there is one pharmaceutical which does stimulate stem cells to migrate to the liver, and that is HGH, (Human Growth Hormone) only available in injection form currently.
There is of course a greater chance of aberant cells forming as well, should dosing be excessive, or the immune system weak and unable to recognize the same.

In any case, it's an interesting topic I hope will get the research dollars it deserves.

Thought maybe we could post things relating to this topic on this thread.

for consideration:

>>>>>>>>>>>>>Is There a Liver Stem Cell?
by Stewart Sell
Department of Pathology and Laboratory Medicine, University of Texas Health Science Center, Houston, Texas 77030

The role of a putative liver stem cell in liver regeneration and carcinogenesis is reviewed. There is increasing evidence that there is a liver stem cell that has the capacity to differentiate into parenchymal hepatocytes or into bile ductular cells. These stem cells may be activated to proliferate after severe liver injury or exposure to hepatocarcinogens. They are not activated by moderate liver injury, which is repaired by proliferation of mature heaptocytes. Exposure to most chemical hepatocarcinogens results in proliferation of a small morphologically indistinct cell population termed "oval cells." These cells have been shown to have the capacity to differentiate into hepatocytes or into ductular cells. The origin of these cells appears to be from transition duct cells, but there is also evidence of an even less mature periportal liver stem cell. Study of the development of these cells during carcinogenesis indicates that liver cancer arises from oval cells by aberrant differentiation of stem cells.
end.

So, judging from the above, I would say the live donor recipient might have a better chance of replacing the needed 2/3 of a liver with more of ones own stem cells and ergo ones own genetic material due to the greater injury calling upon that system to produce cells.
Ergo eventually rejection might be less of an issue for that group.
(this is just my theory based on the above explaination of the constructs. It could be wrong).

Now this brings up what researcch is there into oval cell stimulation as well. Hmm.
mb

[merryBe]

http://www.hopkinsmedicine.org/Press_releases/2004/06_01_04.html

bone marrow stem cells research at John Hopkins

[merryBe]

a genetic cure for liver cancer discovered through stem cell research and why we all need some little ELFs in our lives ; )))))))))))

http://www.sciencedaily.com/releases/2008/02/080208113917.htm

[mikesimon]

Regarding your hypothesis:
"So, judging from the above, I would say the live donor recipient might have a better chance of replacing the needed 2/3 of a liver with more of ones own stem cells and ergo ones own genetic material due to the greater injury calling upon that system to produce cells.
Ergo eventually rejection might be less of an issue for that group. "

From: Living-related versus deceased donor pediatric liver transplantation: a multivariate analysis of technical and immunological complications in 235 recipients.
Pediatric Liver Transplant Program, Université Catholique de Louvain, Saint-Luc University Clinics, Brussels, Belgium. 2007
"......At multivariate analysis: (1) type of donor (DD) was correlated with higher rate of artery thrombosis (p < 0.012); (2) biliary complication rate at 5 years was 29% and 23% for groups LD and DD, respectively (p = 0.451); (3) lower acute rejection incidence could be correlated with type of donor (DD) (p = 0.001), and immunosuppressive therapy (tacrolimus) (p < 0.001). We conclude that (1) according to the multivariate analysis, LT with LD provided similar patient and graft outcome, when compared to DD; (2) a higher rate of artery thrombosis and a lower rate of rejection were observed in group DD; (3) this study confirms the efficacy of tacrolimus for immunoprophylaxis, whatever the type of organ donor is."

From: Do graft type or donor source affect acute rejection rates after liver transplant: a multivariate analysis.
Department of Surgery, University of Minnesota, Minneapolis, MN, USA. 2008

"We looked at acute rejection (AR) rates in adult liver transplant recipients to determine if graft type (whole liver vs. partial liver) or donor source (living vs. deceased donor) influenced the risk for AR. Between 1999 and 2005, we performed 292 whole liver transplants from a deceased donor (DD-WL) and 91 partial transplants, either from a living donor (LDLT, n = 59) or split liver from a deceased donor (DD-SL, n = 32). Pediatric recipients were not included. The groups were well matched by age and type of liver disease (p = ns), but mean model for end-stage liver disease (MELD) scores were higher in the DD-WL vs. LD recipient groups (p < 0.01). Immunosuppression was similar for all. AR rates at 12 months post-transplant were lower in the LDLT group (10.0%) vs. the DD-WL group (16.5%, p = 0.10), although this was not statistically significant. AR rates in the DD-SL transplant group (12.8%) were intermediate compared with the two other groups and not statistically different from either group (p = ns). By multivariate analysis, however, neither graft type (partial vs. whole) nor donor source (LD vs. DD) seemed to have an impact on the risk for AR. The only factor that was associated with an increased risk for AR was not using induction therapy."

From: Marked Differences in acute cellular rejection rates between living-donor and deceased-donor liver transplant recipients.
Recanati/Miller Transplantation Institute, The Mount Sinai Medical Center, New York, NY 10029, USA. 2005

"BACKGROUND.: Due to ongoing organ donor shortage, an increasing number of adult live-donor liver transplants (LDLT) are being performed. The aims of this study were to compare the incidence of ACR between recipients of live- and deceased-donor liver transplants, and to note any differences in ACR among related and unrelated living-donor recipients. METHODS.: Sixty-four adults undergoing LDLT between 1998-2001 were closely matched with a deceased recipient. Statistical comparisons in ACR between the live- and deceased-donor groups were based on the differences between the ACR rates of each LDLT patient and the corresponding matched deceased recipient. Analyses were performed separately for pairs in which the living donor was not related to the recipient, was a nonsibling relative, or was a sibling. RESULTS.: Live- and deceased-donor recipients underwent a similar number of liver biopsies. In all, 16/50 (32%) of the biopsied LDLT patients had ACR compared to 36/49 (73%) of the deceased-donor recipients. ACR rates of living donors and their deceased-donor matches did not differ significantly for the unrelated living donors, but did differ for the nonsibling related (P=0.03) and the sibling LDLT (P=0.03). The results were similar when comparing rates of high-degree ACR for unrelated, nonsibling related, and sibling pairs. High-degree ACR differences in the sibling LDLT group were significantly greater than in the nonsibling group (P=0.05). CONCLUSIONS.: Rates of ACR and high-degree ACR are decreased in living-related liver transplant recipients. This difference is likely genetically related as ACR rates are lower in recipient-donor pairs of increasing genetic similarity."

It doesn't appear as though your theory is borne out in the real world experience - at least not in the information I found

Mike