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Generation of immunocompatible cardiac myocytes for heart repair
Author(s) -
Karabekian Zaruhi,
Idrees Sana,
Sarvazyan Narine
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1043.15
Subject(s) - myocyte , microbiology and biotechnology , major histocompatibility complex , embryonic stem cell , mhc class i , biology , beta 2 microglobulin , downregulation and upregulation , puromycin , small hairpin rna , immunology , antigen , gene , rna , protein biosynthesis , genetics
Background Repair of myocardia with stem cell derived cardiomyocytes (SC‐CM) is becoming increasingly realistic, although major obstacles still exist, including immunorejection of the grafts. Expression of MHC class I (MHC‐I) molecules by grafted cells is the main reason for rejection. Downregulation of MHC molecules in SC‐CM should reduce the immunogenicity of these cells. Results Cardiomyocytes were derived from mouse embryonic SC (CorAt) in which puromycin resistance gene was driven by a cardiac‐specific promoter. CorAt formed beating cardiomyocytes and expressed cardiac specific proteins. The effect of inflammatory stimuli on the expression of MHC‐I molecules was mimicked by IFN‐gamma treatment. MHC‐I expression was reduced by RNA interference against beta2‐microglobulin (light chain) as measured by qPCR. Transduction of CorAt with anti‐beta2‐microglobulin shRNA lentivirus led to a lowered activation of cognate T‐cells when MHC‐I downregulated CorAt were used as targets. Similar results were obtained with W19 fibroblasts, confirming that analogous strategy can be used for a variety of cells. Conclusions The CorAT cells were effective in the repair of ischemic myocardia of syngeneic mice. Making these cells immunocompatible with allo‐ or xenogeneic recipients offers a reliable source of ESC‐CM for small rodents and can be extended to ESC of large mammals for human heart repair.