IPSK: is the risk of developing tumors exaggerated?
Rodent studies often do not provide adequate results when testing new therapeutic approaches, including potential medicines. For example, more than 700 drugs for the treatment of stroke, which demonstrated good results in experiments on rodents, failed in clinical trials. Another confirmation that mice are a cheap, but not the most suitable model for studying human diseases: experiments have shown that 50% of all analyzed chemical compounds, regardless of their nature and source, give positive results in tests conducted on rodents for carcinogenicity. In particular, some components of coffee cause the formation of malignant tumors in rodents, whereas in humans moderate consumption of this drink reduces the risk of cancer. Therefore, a number of experts are of the opinion that conducting such tests, in fact, is no better than tossing a coin.
The tendency to form malignant tumors revealed in experiments on mice raised the question of the safety of the use of induced pluripotent stem cells and their derivatives in clinical practice.
In 2010, University of Georgia researchers Steven L. Stice and Franklin West began using pigs, whose physiology is much closer to human than the physiology of rodents, as objects for studying experimental therapies. Recently, work with pigs has brought another encouraging result: it turned out that induced pluripotent stem cells (iPSCs) obtained from adult cells do not cause the formation of tumors in pig tissues.
To find out, the researchers achieved the birth of transgenic piglets from iPSCs obtained in accordance with a protocol previously developed by Dr. West's group. The pluripotency of porcine iPSCs ensured the expression of the human genes POU5F1, SOX2, NANOG, LIN28, KLF4 and C-MYC embedded in their chromosomes.
At the ages of 2, 7 and 9 months, animal tissue samples were analyzed for the presence of malignant tumors. At the same time, in contrast to the results obtained in similar experiments on mice, no signs of malignancy were detected in tissue samples of various organs (liver, skin, brain, pancreas, stomach, intestines, lungs, heart, kidneys, muscles, spleen and sex glands) of all 11 pigs. There was no expression of C-MYC oncogene in the tissues, which poses the greatest danger from the point of view of IPSC malignancy.
According to Dr. Stice, the possibility of therapeutic use of iPSCs without the risk of tumor formation is a prerequisite for the introduction of such therapies into clinical practice. He also argues that the creation of porcine iPSCs that do not cause the formation of malignant tumors in the body of young animals is the basis of a very attractive model for studying the effectiveness and safety of cell therapy methods and, possibly, the creation of complex transgenic animals.
Moreover, the researchers were able to crossbreed pigs raised from iPSCs and demonstrate that the expression of human genes is transmitted to the next generation. This discovery opens up new opportunities for regenerative medicine – for example, transplantation of low-immunogenic insulin-producing cells of transgenic chimeric pigs to patients with diabetes mellitus.
Article by Franklin D. West et al. Brief Report: Chimeric Pigs Produced from Induced Pluripotent Stem Cells Demonstrate Germline Transmission and No Evidence of Tumor Formation in Young Pigs published in Stem Cells journal.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of Georgia:
Pig-induced pluripotent stem cells may be safer than previously thought.
12.12.2011