Immunological Responses to Transgene-Modified Neural Stem Cells After Transplantation
| Autor: | Peiqi Zheng, Yanfei Jia, Zhenxing Sun, Hailiang Tang, Jimei Yu, Jian Chen, Naili Wei |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
DNA Bacterial Transgene Immunology Green Fluorescent Proteins Transplantation Heterologous mms6 Major histocompatibility complex Kidney 03 medical and health sciences 0302 clinical medicine Immune system Downregulation and upregulation Neural Stem Cells Immunology and Allergy Animals Humans Transgenes Magnetospirillum Magnetite Nanoparticles Cells Cultured Original Research Cell Proliferation immunological response biology Brain magnetotactic bacteria RC581-607 Embryonic stem cell Neural stem cell major histocompatibility complex Recombinant Proteins Rats Transplantation 030104 developmental biology HEK293 Cells nervous system Genes Bacterial Astrocytes Cancer research biology.protein Magnetosomes Microglia Immunologic diseases. Allergy Stem cell 030217 neurology & neurosurgery Spleen transgenic modification Stem Cell Transplantation |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 12 (2021) |
| ISSN: | 1664-3224 |
| Popis: | Neural stem cell (NSC) therapy is a promising therapeutic strategy for stroke. Researchers have frequently carried out genetic modification or gene editing of stem cells to improve survival or therapeutic function. However, NSC transplantation carries the risk of immune rejection, and genetic modification or gene-editing might further increase this risk. For instance, recent studies have reported on manipulating the stem cell genome and transplantationviathe insertion of an exogenous gene derived from magnetotactic bacteria. However, whether transgene-modified stem cells are capable of inducing immunological reactions has not been explored. Although NSCs rarely express the major histocompatibility complex (MHC), they can still cause some immunological issues. To investigate whether transgene-modified NSCs aggravate immunological responses, we detected the changes in peripheral immune organs and intracerebral astrocytes, glial cells, and MHC-I and MHC-II molecules after the injection of GFP-labeled ormms6-GFP-labeled NSCs in a rat model. Xenogeneic human embryonic kidney (HEK-293T) cells were grafted as a positive control group. Our results indicated that xenogeneic cell transplantation resulted in a strong peripheral splenic response, increased astrocytes, enhanced microglial responses, and upregulation of MHC-I and MHC-II expression on the third day of transplantation. But they decreased obviously except Iba-1 positive cells and MHC-II expression. When injection of bothmms6-GFP-labeled NSCs and GFP-labeled NSCs also induced similar responses as HEK-293T cells on the third days, but MHC-I and MHC-II expression decreased 3 weeks after transplantation. In addition,mms6transgene-modified NSCs did not produce peripheral splenic response responses as well as astrocytes, microglial cells, MHC-I and MHC-II positive cells responses when compared with non-modified NSCs. The present study provides preliminary evidence that transgenic modification does not aggravate immunological responses in NSC transplantation. |
| Databáze: | OpenAIRE |
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