Uterine-derived progenitor cells are immunoprivileged and effectively improve cardiac regeneration when used for cell therapy. (July 2015)

• Record Type: Journal Article
• Authors: Ludke, Ana; Wu, Jun; Nazari, Mansoreh; Hatta, Kota; Shao, Zhengbo; Li, Shu-Hong; Song, Huifang; Ni, Nathan C.; Weisel, Richard D.; Li, Ren-Ke
• Is Part Of: Journal of molecular and cellular cardiology. Volume 84(2015:Jul.)
• Page Start: 116
• Page End: 128
• Publication Date: 2015-07
• Subjects: Stem cell -- Uterus -- Immune tolerance -- Cell therapy -- Myocardial infarction; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2015.04.019
• Languages: English
• ISSNs: 0022-2828

Abstract

ABSTRACT: Cell therapy to prevent cardiac dysfunction after myocardial infarction (MI) is less effective in aged patients because aged cells have decreased regenerative capacity. Allogeneic transplanted stem cells (SCs) from young donors are usually rejected. Maintaining transplanted SC immunoprivilege may dramatically improve regenerative outcomes. The uterus has distinct immune characteristics, and we showed that reparative uterine SCs home to the myocardium post-MI. Here, we identify immunoprivileged uterine SCs and assess their effects on cardiac regeneration after allogeneic transplantation. We found more than 20% of cells in the mouse uterus have undetectable MHC I expression by flow cytometry. Uterine MHC I (neg) and MHC I (pos) cells were separated by magnetic cell sorting. The MHC I (neg) population expressed the SC markers CD34, Sca-1 and CD90, but did not express MHC II or c-kit. In vitro, MHC I (neg) and (pos) SCs show colony formation and endothelial differentiation capacity. In mixed leukocyte co-culture, MHC I (neg) cells showed reduced cell death and leukocyte proliferation compared to MHC I (pos) cells. MHC I (neg) and (pos) cells had significantly greater angiogenic capacity than mesenchymal stem cells. The benefits of intramyocardial injection of allogeneic MHC I (neg) cells after MI were comparable to syngeneic bone marrow cell transplantation, with engraftment in cardiac tissue and limited recruitment of CD4 and CD8 cells up to 21 days post-MI. MHC I (neg) cells preserved cardiac function, decreased infarct size and improved regeneration post–MI. This new source of immunoprivileged cells can induce neovascularization and could be used as allogeneic cell therapy for regenerative medicine. Highlights: Identification of uterine progenitor cells with distinct immunoprivilege abilities These uterine cells are highly angiogenic and show regenerative capacity. Uterine MHC I (neg) cells can be used as allogeneic cell therapy for cardiac repair. MHC I (neg) cells show improved engraftment and regeneration after infarction. These immunoprivileged cells may represent a promising therapy for ischemic injury.