Dystrophin conferral using human endothelium expressing HLA-E in the non-immunosuppressive murine model of Duchenne muscular dystrophy.
Human leukocyte antigen (HLA)-E is a non-classical major histocompatibility complex class I (Ib) molecule, which plays an important role in immunosuppression. In this study, we investigated the immunomodulating effect of HLA-E in a xenogeneic system, using human placental artery-derived endothelial (hPAE) cells expressing HLA-E in a mouse model. In vitro cell lysis analysis by primed lymphocytes in combination with siRNA transfection showed that HLA-E is necessary for inhibition of the immune response. Similarly, in vivo cell implantation analysis with siRNA-mediated down-regulation of HLA-E demonstrates that HLA-E is involved in immunosuppression. As hPAE cells efficiently transdifferentiate into myoblasts/myocytes in vitro, we transplanted the cells into mdx mice, a model of Duchenne muscular dystrophy. hPAE cells conferred dystrophin to myocytes of the 'immunocompetent' mdx mice with extremely high efficiency. These findings suggest that HLA-E-expressing cells with a myogenic potential represent a promising source for cell-based therapy of patients with muscular dystrophy.
Cui
Chang-Hao
CH
Department of Reproductive Biology, National Institute for Child Health and Development, Tokyo, Japan.
Miyoshi
Shunichiro
S
Tsuji
Hiroko
H
Makino
Hatsune
H
Kanzaki
Seiichi
S
Kami
Daisuke
D
Terai
Masanori
M
Suzuki
Harumi
H
Umezawa
Akihiro
A
D000818:Animals; D001158:Arteries / Q000166:cytology; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D016189:Dystrophin / Q000235:genetics* / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007121:Immunocompetence / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018101:Mice, Inbred mdx; D024510:Muscle Development / Q000235:genetics; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D000097625:HLA-E Antigens
D016189:Dystrophin; D015395:Histocompatibility Antigens Class I; D034741:RNA, Small Interfering; D000097625:HLA-E Antigens