Project Summary/Abstract for, “Transplantation of MHC homozygous vascular progenitors in primates.”
For tissue engineered arteries, the use of patient specific iPS cells would be severely limited by time
constraints and cost. Banking iPS cells from rare individuals homozygous for HLA alleles has been proposed
as a strategy to allow economies of scale, while still reducing rejection of iPS cell-derived transplanted tissues.
Only a few hundred such cell lines would provide matches for the majority of the U.S. population, and the
Waisman Clinical Biomanufacturing facility here on the University of Wisconsin has already produced cGMP
HLA homozygous iPS cell lines. However, the immunological value of such an approach remains untested in
an animal model with an immune system similar to the human immune system.
Here we will use a unique population of MHC defined cynomolgus monkeys to test the immune
response to MHC homozygous cynomolgus iPS cell-derived vascular cells transplanted to MHC haploidentical
recipients. Using the MHC defined cynomolgus monkeys, we will use a limb ischemia model to determine the
ability of iPS cell-derived arterial endothelial cells to contribute to collateral circulation when transplanted by
themselves, in combination with iPS cell-derived smooth muscle cells, or when combined into a fully tissue
engineered artery. A central premise of this proposal is that properly specified early arterial endothelial cells
will robustly recruit, expand, and mature endogenous or co-transplanted smooth muscle cell progenitors to
increase arteriogenesis in vivo, and that these arterial endothelial cells will be critical to producing tissue
engineered arteries ex vivo that remain functional long after transplantation. The final goal of this proposal is
to produce cGMP vascular progenitors from HLA homozygous human iPS cell lines for the pre-clinical animal
studies required to file an IND for critical limb ischemia. With extensive human and primate pluripotent stem
cell expertise, a strong bioengineering department, a National Primate Research Center with an MHC typing
facility, and a GMP cell manufacturing facility, the environment at the University of Wisconsin is uniquely suited
for completing the goals of this proposal.