DA neurons derived from hES cells that express HLA-G1 are capable of immunosuppression.
Human embryonic stem (hES) cells have the capacity for self-renewal and exhibit multipotentiality. hES cells have promise for serving as an unlimited source of ideal seed cells for cell transplantation. However, the rejection that occurs between the transplant recipient and the transplanted cell poses a major challenge for therapeutic transplantation. This study was designed to devise methods to enhance immune tolerance in cell therapy. We established an hES cell line that could stably express human leukocyte antigen-G1 (HLA-G1). The established HLA-G1-H1 hES cells still retained all the characteristics of normal human embryonic stem cells. By using the SDIA method, we induced dopaminergic (DA) neurons by coculturing HLA-G1-H1 hES cells with the mouse stromal cell line PA6. Tyrosine hydroxylase (TH)+neurons were detected on the 10th day of differentiation, and 70% of the HLA-G1-H1 hES cells were TH+mature DA neurons because the differentiation time was only 3 weeks. Cells that had been differentiating for different periods of time still expressed HLA-G1, and these differentiated DA neurons released dopamine and other catecholamines in response to K+ depolarization as measured by HPLC. After careful study, we found that HLA-G1-H1 hES cells are capable of inhibiting the proliferation of mixed T-lymphocytes. DA neurons derived from HLA-G1-H1 hES attenuated the release of proinflammatory cytokines IL-1β and IFN-γ from lipopolysaccharide (LPS)-stimulated BV2 microglia. The efficiency of inhibition was significant and dose-dependent. This method might be used to treat Parkinson's patients via cell transplantation.
Department of Obstetrics and Gynecology, the General Hospital of the People's Liberation Army (PLA), Fuxing Road 28, Beijing 100853, PR China.
Yajing
Y
Zhu
Hongxi
H
Zhao
Li
L
Wang
Sanjun
S
Zhao
Feng
F
Jiang
Lingsong
L
Li
Yuanqing
Y
Yao
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000276:immunology*; D053595:Embryonic Stem Cells / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006131:Growth Inhibitors / Q000502:physiology; D057809:HEK293 Cells; D059951:HLA-G Antigens / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice
D006131:Growth Inhibitors; D059951:HLA-G Antigens