Human and nonhuman primate embryonic stem cells (ESC) have the potential to provide unlimited supplies of healthy cells for the implementation of regenerative medicine and the reconstitution of diseased organs. Yet, equally significant is their potential for providing insights into fundamental principles and mechanisms of early human development. One of the greatest gaps in our knowledge is at the periimplantation stage of human embryonic development, due to limitations on the experimental use of human embryos. We have developed a paradigm with human ESC-derived embryoid bodies which promotes the initiation of trophoblast differentiation, and enhances their differentiated function by culture in extracellular matrix environments. Yet, limitations remain in the use of human cells for in vivo experiments. We thus propose to adapt this in vitro paradigm to rhesus monkey ESC (rESC) and expand it to an in vivo implantation model with rESC-derived embryoid bodies with 2 specific aims:
Specific Aim 1. To define trophoblast formation and differentiation (including MHC class I expression) in rESC in response to soluble factors, extracellular matrix environments, and transcriptional intervention.
Specific Aim 2. To perform in vivo transfer of rhesus embryoid bodies to evaluate trophoblast differentiation and endometrial responses at a eutopic uterine site. Few models exist for research specifically relevant to human embryonic development and implantation. The embryoid body (EB) model shows substantial promise in allowing the study of human placental morphogenesis, based on functional and morphological correlates of trophoblast function. Our proposed studies will establish a nonhuman primate resource to model placental development and morphogenesis. In addition, the definition of the MHC expression within rhesus ES cells and their derivatives has significance for transplantation biology and immunology as well as implantation biology and development of the extraembryonic fetal membranes. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Project (R01)
Project #
1R01RR021876-01A1
Application #
7098354
Study Section
Pregnancy and Neonatology Study Section (PN)
Program Officer
Harding, John D
Project Start
2006-04-01
Project End
2010-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
1
Fiscal Year
2006
Total Cost
$466,777
Indirect Cost
Name
University of Wisconsin Madison
Department
Veterinary Sciences
Type
Other Domestic Higher Education
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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Rozner, Ann E; Durning, Maureen; Kropp, Jenna et al. (2016) Macrophages modulate the growth and differentiation of rhesus monkey embryonic trophoblasts. Am J Reprod Immunol 76:364-375
Golos, T G; Giakoumopoulos, M; Gerami-Naini, B (2013) Review: Trophoblast differentiation from human embryonic stem cells. Placenta 34 Suppl:S56-61
Giakoumopoulos, M; Golos, T G (2013) Embryonic stem cell-derived trophoblast differentiation: a comparative review of the biology, function, and signaling mechanisms. J Endocrinol 216:R33-45
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Bondarenko, Gennadiy I; Durning, Maureen; Golos, Thaddeus G (2012) Immunomorphological changes in the rhesus monkey endometrium and decidua during the menstrual cycle and early pregnancy. Am J Reprod Immunol 68:309-21
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Rozner, Ann E; Dambaeva, Svetlana V; Drenzek, Jessica G et al. (2009) Generation of macrophages from peripheral blood monocytes in the rhesus monkey. J Immunol Methods 351:36-40