(From the December 2013 issue of Research Now)
Alpha-1-antitrypsin deficiency is a common and serious genetic disorder associated with emphysema and liver disease due to mutations in a gene encoding a peptidase inhibitor. In the US, the prevalence of such mutant alleles is approximately 1 in 11. Orthotopic liver transplantation is currently the only curative option for children and adults with progressive liver dysfunction and failure. Dr. John McLaughlin’s lab is evaluating the capacity of embryonic stem cell derivatives to ameliorate liver disease in transgenic mice modeling alpha-1-antitrypsin deficiency. One approach centers on using parthenogenetic embryonic stem cells that are derived from the oocytes of affected heterozygous mice. A subset of these stem cells does not contain the disease-bearing mutation, and could therefore provide a source of mutation free but autologous material for tissue transplantation.
Espejel S, Roll GR, McLaughlin KJ, Lee AY, Zhang JY, Laird DJ, Okita K, Yamanaka S, Willenbring H. Induced pluripotent stem cell-derived hepatocytes have the functional and proliferative capabilities needed for liver regeneration in mice. The Journal of Clinical Invesigation. 2010 Sep, 120(9):3120-6.
Eckardt S, Yanchik A, Leu NA, Hatada S, Kyba M, and McLaughlin KJ. Gene therapy by allele selection in a mouse model of beta-thalassemia. The Journal of Clinical Investigation. 2011Feb 1, 121(2):623-7.