title: Molecular imaging of induced pluripotent stem cell immunogenicity with in vivo development in ischemic myocardium.
abstract: Whether differentiation of induced pluripotent stem cells (iPSCs) in ischemic myocardium enhances their immunogenicity, thereby increasing their chance for rejection, is unclear. Here, we dynamically demonstrated the immunogenicity and rejection of iPSCs in ischemic myocardium using bioluminescent imaging (BLI). Murine iPSCs were transduced with a tri-fusion (TF) reporter gene consisting of firefly luciferase-red fluorescent protein-truncated thymidine kinase (fluc-mrfp-tTK). Ascorbic acid (Vc) were used to induce iPSCs to differentiate into cardiomyocytes (CM). iPSCs and iPS-CMs were intramyocardially injected into immunocompetent or immunosuppressed allogenic murine with myocardial infarction. BLI was performed to track transplanted cells. Immune cell infiltration was evaluated by immunohistochemistry. Syngeneic iPSCs were also injected and evaluated. The results demonstrated that undifferentiated iPSCs survived and proliferated in allogenic immunocompetent recipients early post-transplantation, accompanying with mild immune cell infiltration. With in vivo differentiation, a progressive immune cell infiltration could be detected. While transplantation of allogenic iPSC-CMs were observed an acute rejection from receipts. In immune-suppressed recipients, the proliferation of iPSCs could be maintained and intramyocardial teratomas were formed. Transplantation of syngeneic iPSCs and iPSC-CMs were also observed progressive immune cell infiltration. This study demonstrated that iPSC immunogenicity increases with in vivo differentiation, which will increase their chance for rejection in iPSC-based therapy.
authors.affiliation: Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing, PR China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Liu
authors.forename: Xinyu
authors.initials: X
authors.lastname: Wen
authors.forename: Haibin
authors.initials: H
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.forename: Mengge
authors.initials: M
authors.lastname: Zhao
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Lin
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Junjie
authors.initials: J
authors.lastname: Li
authors.forename: Dexue
authors.initials: D
authors.lastname: Li
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Du
authors.forename: Anning
authors.initials: A
authors.lastname: Yao
authors.forename: Feng
authors.initials: F
authors.lastname: Cao
authors.forename: Changyong
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D016923:Cell Death; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D058948:Cell Tracking; D005260:Female; D017930:Genes, Reporter; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D057026:Induced Pluripotent Stem Cells / Q000276:immunology / Q000502:physiology / Q000637:transplantation*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000276:immunology / Q000628:therapy*; D009206:Myocardium / Q000276:immunology / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000276:immunology / Q000637:transplantation*; D013724:Teratoma / Q000473:pathology; D014161:Transduction, Genetic; D051598:Whole Body Imaging