title: Inhibition of DNA methylation enhances HLA-G expression in human mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) are immunosuppressive multipotent cells under investigation for potential therapeutic applications in regenerative medicine and prevention of graft-versus-host disease. Human leukocyte antigen (HLA)-G contributes to the immunomodulatory properties of MSCs. HLA-G expression in MSCs is very low and diminishes during in vitro expansion. Epigenetic regulation activates HLA-G expression in some cancer cell lines but not in MSCs. In the present study, adipose- and bone marrow-derived MSCs were exposed to the DNA demethylating agent 5-aza-2-deoxycytidine (5-aza-dC) and histone deacetylase inhibitor valproic acid (VPA) and HLA-G mRNA levels assessed using semi-quantitative reverse-transcription PCR. Exposure to 5-aza-dC resulted in HLA-G1 and -G3 upregulation in both early and late passage MSCs. VPA treatment did not induce HLA-G expression in both bone marrow and adipose derived MSCs. Our results provide the first evidence that HLA-G3 could be expressed in MSCs and that methylation-mediated repression is partly responsible for the observed low levels of HLA-G expression in MSCs. Our findings provide insight that treatment of MSCs with specific epigenetic regulatory modulators may improve their immunoregulatory capability for therapeutic applications.
authors.affiliation: Escape Therapeutics, Inc., San Jose, CA, United States.
authors.forename: Takele
authors.initials: T
authors.lastname: Teklemariam
authors.affiliation: San Jose State University, San Jose, CA, United States.
authors.forename: Bhamini
authors.initials: B
authors.lastname: Purandare
authors.affiliation: Escape Therapeutics, Inc., San Jose, CA, United States.
authors.forename: Longmei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Escape Therapeutics, Inc., San Jose, CA, United States. Electronic address: basil@escapetherapeutics.com.
authors.forename: Basil M
authors.initials: BM
authors.lastname: Hantash
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D044127:Epigenesis, Genetic; D059951:HLA-G Antigens / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D059951:HLA-G Antigens; D012333:RNA, Messenger; D014635:Valproic Acid; D000077209:Decitabine; D001374:Azacitidine
keywords: 5-aza-2-deoxycytidine; Epigenetic regulation; HLA-G; Immunomodulation; Mesenchymal stem cells; Valproic acid