Thomson (UW-M) Research Hub 05

James A. Thomson, VMD, MD

U01 Principal Investigator, 1-U01HL134655-01

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.  

members: 
Lead Principal Investigator
User Name Full Name Institute Affiliation Topic tags People tags
jthomson's picture
jthomson James A. Thomson, M.D., Ph.D. University of Wisconsin
Co-PI/Co-Investigator
User Name Full Name Institute Affiliation Topic tags People tags
nchesler's picture
nchesler Naomi Chesler, PhD University of Wisconsin-Madison
spoore's picture
spoore Samuel Poore, MD, PhD University of Wisconsin School of Medicine and Public Health
islukvin's picture
islukvin Igor Slukvin, M.D., Ph.D. University of Wisconsin-Madison
tturng's picture
tturng Lih-Sheng (Tom) Turng, PhD University of Wisconsin-Madison
Post-Doctoral Fellow/Trainee
User Name Full Name Institute Affiliation Topic tags People tags
Mbrown's picture
Mbrown Matthew Brown Ph.D. University of Wisconsin-Madison
Dvereide's picture
Dvereide David Vereide Ph.D. Morgridge Institute for Research
juzhang's picture
juzhang Jue Zhang, Ph.D. Morgridge Institute
Publication: 
Author(s) Title Link
Mi Ae Park, Akhilesh Kumar, Ho Sun Jung, Gene Uenishi, Oleg V. Moskvin, James A. Thomson, Igor I. Slukvin Activation of the Arterial Program Drives Development of Definitive Hemogenic Endothelium with Lymphoid Potential view
Gene I. Uenishi, Ho Sun Jung, Akhilesh Kumar, Mi Ae Park, Brandon K. Hadland, Ethan McLeod, Matthew Raymond, Oleg Moskvin, Catherine E. Zimmerman, Derek J. Theisen, Scott Swanson, Owen J. Tamplin, Leonard I. Zon, James A. Thomson, Irwin D. Bernstein & Igor I. Slukvin NOTCH Signaling Specifies Arterial-Type Definitive Hemogenic Endothelium from Human Pluripotent Stem Cells view
Matthew Brown, Ying Zhou, James Thomson, et al A Humanized Mouse Model Generated Using Surplus Neonatal Tissue view
Jue Zhang, Li-Fang Chu, James Thomson Functional Characterization of Human Pluripotent Stem Cell-Derived Arterial Endothelial Cells view
Akhilesh Kumar; Saritha Sandra D’Souza; Oleg V. Moskvin; Huishi Toh; Bowen Wang; Jue Zhang; Scott Swanson; Lian-Wang Guo; James A. Thomson; Igor I. Slukvin Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts view

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