Transplantation immunity phenomena after embryonic stem cell-derived neural progenitor cells are grafted into ischemic rat brain

doi:10.3969/j.issn.2095-4344.2014.14.010

Abstract

Abstract:

BACKGROUND: Previous studies have showed inconsistent results in the immunogenicity of neural progenitor cells and further studies are required to confirm the model of immune response after transplantation in vivo.
OBJECTIVE: To observe the constitutive and inducible expression of major histocompatibility complex (MHC) molecules on neural progenitor cells in vitro and the local immune cell activation in lesion tissue after neural progenitor cells grafted in ischemic rat brain, so as to explore the possibility and model of graft rejection of neural progenitor cells.
METHODS: Neural progenitor cells were differentiated from pCX-eGFP ES-D3 embryonic stem cells and the constitutive and interferon-γ-induced expression of MHC class I and II molecules on neural progenitor cells was
observed in vitro by flow cytometry. Neural progenitor cells were then injected into the lateral ventricle of model animals after middle cerebral artery occlusion (MCAO) or sham surgery which were subdivided into the three groups as MCAO+neural progenitor cells injection group, MCAO+PBS injection group and sham+PBS injection group. A histological evaluation of ED1, CD8 and CD4 positive cells infiltration in the striatum and a proliferation assay of lymphocytes dissociated from cervical lymphnodes were performed after cell transplantation.
RESULTS AND CONCLUSION: High constitutive expression of class I but no II MHC molecules was found on the surface of neural progenitor cells by flow cytometry. After interferon-γ induction, a further increase in class I molecules and a mild but detectable upregulation of class II molecules were found, suggesting the possibility of immune response initiated by neural progenitor cells because of the constitutive expression of class I and the inducible expression of MHC II molecules on cell surface. Rats in the MCAO+neural progenitor cells injection and MCAO+PBS injection group had a higher ED1+,CD4+ and CD8+ cells infiltration in the striatum compared with those in the sham group (P < 0.05). Rats in the MCAO+neural progenitor cells group showed even higher ED1+, CD4+ cells infiltration compared with those in the MCAO+PBS injection group (P < 0.05), suggesting that ischemic lesion itself was the main cause for the immunoreactions in brain, whereas the higher infiltration of CD4+ and ED1+ cells in the striatum of rats undergoing neural progenitor cell transplantation, indicating there is also a possible graft rejection directed to neural progenitor cells through CD4+-Th1 pathway. Compared with sham animals, rats in MCAO+neural progenitor cells injection group and MCAo+PBS injection group showed significantly higher lymphocytes proliferation (P < 0 .01), but there was no difference in lymphocytes proliferation between MCAO+neural progenitor cells and MCAO+PBS groups (P > 0.05). This suggests that neural progenitor cells in vitro alone cannot trigger a significant proliferation of lymphocytes.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

全文链接：

Key words: stem cells, brain ischemia, major histocompatibility complex, transplantation immunology

CLC Number:

R394.2

Mei Ai-nong, Zhang Su-ming. Transplantation immunity phenomena after embryonic stem cell-derived neural progenitor cells are grafted into ischemic rat brain[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(14): 2191-2199.

Figures/Tables 4

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