For many life-threatening medical conditions, the only treatment option is organ transplantation. However, organs are constantly in short supply; because of this shortage, over 10,000 people in the US die each year while waiting for an organ to become available. But, what if it was possible to produce cells in sufficient quantities to replace our organs when they fail? This is the promise of regenerative medicine, a field that started with the discovery that it is possible to produce, in vitro, several of our body's cell types. The liver has been shown to be especially amenable to cellular regeneration. However, the crucial obstacle has been the need to generate sufficient quantities of liver cells in an economically feasible manner.

Dr. Gary Peltz, Professor of Anesthesia, and his laboratory at Stanford University have developed a technology to convert fat cells into liver cells, quickly and at a reasonable cost. This technology will help patients with liver failure by enabling the fat obtained from a standard liposuction procedure to be used to produce enough hepatocytes to regenerate an entire human liver.

The Peltz lab is committed to bringing this technology to the clinic in the near future. This will enable patients with liver failure, who presently must hope that a liver will become available and then must undergo a major surgery, to be treated with a simple infusion of cells.

Current projects in the Peltz Lab include:

• Regenerative Medicine for Liver Failure: Dr. Peltz and his team are developing “induced hepatocyte” technology for treatment of patients with life-threatening liver disease. The cells are derived from the stem cells present in fat tissue. The amount of material obtained from a standard liposuction procedure can be used to produce enough hepatocytes to replace an entire human liver, and the conversion to hepatocytes is completed in nine days at an affordable cost. They have designed and are working to execute a phase one clinical trial at Stanford University to test this liver regeneration method.
• Using Mice with Humanized Livers to Make Safer Drugs: In 1993, seven subjects that were treated with a drug against hepatitis B virus infection (fialuridine) as part of a clinical trial, developed acute liver failure and died. This drug was thought to be safe for human use; since preclinical studies in mice, rats, dogs, and primates did not provide any indication of toxicity. As this tragedy demonstrates, we often do not know what will happen when drugs are first administered to humans, which increases the danger to human subjects during the early stages of drug development. To reduce these risks, Dr. Peltz has developed a mouse with a humanized liver, which can be used to better identify drugs that will cause human liver toxicity. The methods for efficiently producing these humanized mice were painstakingly optimized in the Peltz lab. By using this platform, we will be able to more accurately predict the pattern of drug metabolism in humans and assess their potential for causing human liver toxicity, which will improve drug safety. Moreover, the humanized mice can be used to identify human pharmacogenetic factors and to develop strategies for personalized medicine.
• Preventing Narcotic Drug Withdrawal in Babies: In the United States, one baby per hour is born to a mother that consumes narcotics, and the vast majority of these babies will develop narcotic drug withdrawal complications. These babies will spend their first month of life in the neonatal intensive care unit. Dr. Peltz developed a computational method for identifying the genetic factors affecting drug and disease susceptibility in mice. This method was used to identify 21 genetic factors affecting biomedical responses. One of the genetic discoveries was that 5HT3 receptor alleles affect susceptibility to dependence upon narcotic drugs. Dr. Peltz and his team demonstrated that a commonly used drug (ondansetron) that inhibits this receptor alleviated narcotic drug withdrawal symptoms in mice. This was quickly confirmed in a translational study performed in normal human volunteers. In an ongoing NIH-funded clinical trial, which involves five medical centers, Dr. Peltz is testing the effectiveness of ondansetron for preventing the development of drug withdrawal symptoms in babies born to narcotic drug-consuming mothers.