Historical Perspectives and Advances in Mesenchymal Stem Cell Research for the Treatment of Liver Diseases.

Liver transplantation is the only effective therapy for patients with decompensated cirrhosis and fulminant liver failure. However, due to a shortage of donor livers and complications associated with immune suppression, there is an urgent need for new therapeutic strategies for patients with end-stage liver diseases. Given their unique function in self-renewal and differentiation potential, stem cells might be used to regenerate damaged liver tissue. Recent studies have shown that stem cell-based therapies can improve liver function in a mouse model of hepatic failure. Moreover, acellular liver scaffolds seeded with hepatocytes produced functional bioengineered livers for organ transplantation in preclinical studies. The therapeutic potential of stem cells or their differentiated progenies will depend on their capacity to differentiate into mature and functional cell types after transplantation. It will also be important to devise methods to overcome their genomic instability, immune reactivity, and tumorigenic potential. We review directions and advances in the use of mesenchymal stem cells and their derived hepatocytes for liver regeneration. We also discuss the potential applications of hepatocytes derived from human pluripotent stem cells and challenges to using these cells in treating end-stage liver disease.

Liver transplantation in Turkey: historical review and future perspectives.

Since the first successful liver transplantation by Starzl et al. in 1967, liver transplantation has become the standard therapy for many liver diseases, mainly chronic liver disease. Most liver transplantations performed in Europe and North America utilize deceased donors while a considerable portion of organ requirements is supplied by living donors in Asian countries including Turkey. The actual history of solid organ transplantation in Turkey began with the pioneering work of Dr. Haberal in collaboration with Thomaz E. Starzl in 1974 in Colorado University at Denver. The first successful solid organ transplantation in Turkey was accomplished by Haberal in 1975 with a living donor renal transplantation. Subsequently, legislations no 2238 and 2594 dated 1979 and 1982, respectively, were passed, paving the way for cadaveric tissue/organ utilization and preservation in Turkey. The first deceased donor liver transplantation and the first living donor liver transplantation were performed in 1988 and 1990, respectively. There are currently 45 liver transplantation centers in Turkey. Of these, 25 are state universities, 8 are private (foundation) universities, 9 are private hospitals, and 3 are training and research hospitals belonging to the Ministry of Health. A total of 7152 liver transplantations were performed in Turkey between January 2002 and May 2014. Of these, 4848 (67.8%) used living donors and 2304 (32.2%) used deceased donors. These figures indicate that, despite widespread organ donation campaigns and media-sponsored propaganda, desired targets have not been met yet in providing deceased organ donation. Despite unsatisfactory levels attained in supplying deceased donors, both the number of annual liver transplantations and improvements in overall survival rates of organ transplanted patients continues to increase. Actually, the one-year patient survival rate after liver transplantation in 2013 was 80.5%. This rate is getting better with each passing year and believed to be close to 90% in the next few years.

The history of liver transplantation in Turkey.

Liver transplantation is the definitive treatment for end-stage liver diseases. The first successful liver transplant was performed in the United States by Thomas Starzl in 1967. The first successful solid organ transplant in Turkey was a living-related kidney transplant performed by Dr. Haberal in 1975. After much effort by Dr. Haberal, the Turkish parliament enacted a law about organ transplantation in 1979. After clinical and experimental studies, the first liver transplant in Turkey was performed by Dr. Haberal in 1988. The first successful partial living-donor liver transplant in children in Turkey was performed by the same team on March 15, 1990. On April 24, 1990, the first living-donor liver transplant was performed on a child in Turkey using a left lateral segment by Dr. Haberal and coworkers. On May 16, 1992, Dr. Haberal performed a simultaneous living-donor liver and kidney transplantation to an adult from the same donor. There currently are 30 liver transplantation centers in Turkey. According to data from the Ministry of Health, there presently are 2065 patients in Turkey who are waiting for a liver transplantation. From January 2002 to June 2013, there were 6091 liver transplants performed in Turkey (4020 living-donor [66% ] and 2071 deceased donor liver transplants [34% ]). From January 2011 to June 2013, there were 2514 patients who had liver transplants in Turkey, and 437 patients (17%) died. The number of liver transplants per year in Turkey reached 1000 transplants in 2012 and more than 1150 transplants in 2013 (15.1/million/y). Therefore, Turkey has one of the highest volumes of liver transplantation per population worldwide, with 90% survival within 1 year after transplantation.