Stem cells against liver cirrhosis
Johns Hopkins University researchers have demonstrated that liver cells derived from reprogrammed cells of various adult tissues take root and repair liver tissue of mice with chronic cirrhosis.
Scientists believe that the approach they have developed in the future will allow obtaining large amounts of functional hepatocytes to restore liver tissue of people in need of transplantation of this organ. The use of such cells will avoid problems associated with the development of rejection of transplants obtained from donors or grown from embryonic stem cells.
The cells of an adult organism, which are returned to the embryonic state with the help of a complex of manipulations, are called induced pluripotent stem cells (iPSCs). These cells have the ability to transform and give rise to various types of body tissues.
The liver has a unique ability to self-repair, which, unfortunately, is lost in the final stages of kidney failure caused by cirrhosis or cancer. To date, the only option for such patients is the transplantation of a donor organ or liver cells. Given the shortage of donor material, as well as the complexity of working with both mature and liver stem cells in the laboratory, induced pluripotent stem cells, a huge number of which can be obtained from a small sample of adult tissue and cultivated in the laboratory indefinitely, look like a very attractive alternative.
As part of the study, scientists obtained induced pluripotent stem cells from several types of adult human cells, including liver hepatocytes, connective tissue fibroblasts, bone marrow stem cells and skin cells. Despite the similarity of the general molecular profile, all the obtained cells retained molecular characteristics that indicate their origin.
After that, iPSCs were differentiated into immature, and then into more mature hepatocytes using chemical signals. Regardless of their origin, cells of all lines have demonstrated the same ability to transform into liver cells.
At the next stage of the work, mice with induced cirrhosis of the liver were injected with 2 million human liver cells derived from induced pluripotent stem cells, or 2 million ordinary human hepatocytes. As a result, 8-15% of transplanted cells took root in the first group of animals, which is comparable to the 11% level of engraftment characteristic of adult liver cells (in the picture - yellow human hepatocytes against the background of blue mouse liver tissue 2 months after transplantation).
The results of laboratory tests demonstrated the functionality of the engrafted cells, since proteins secreted by human liver cells, including albumin, alpha-1-antitrypsin, transferrin and fibrinogen, were detected in the blood of animals that underwent transplantation of induced pluripotent stem cells.
The researchers note that before planning clinical trials, they still have to clarify a number of issues. One of the aspects requiring study is the potential ability of induced pluripotent stem cells to form tumors in the recipient's body. However, the authors claim that during this work, during 7 months of observation (which corresponds to more than 30 years of human life), no tumors were registered in animals. They also plan to analyze the possible influence of the "molecular memory" that induced pluripotent stem cells can retain on their future fate.
Article by H. Liu et al. In Vivo Liver Regeneration Potential of Human Induced Pluripotent Stem Cells from Diverse Origins is published in the journal Science Translational Medicine.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on Johns Hopkins Medical Institutions: Stem Cells Take Root in Livers and Repair Damage.
25.05.2011