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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Wang, Xiaokai Lu, Meng Tian, Xiaoyu Ren, Yansong Li, Yijun Xiang, Meng Chen, Sifeng |
| Abstract | Background Stem cells, including induced pluripotent stem cells (iPSCs), have tremendous potential in health care, though with several significant limitations. Each of the limitations, including immunogenicity, may block most of the therapeutic potentials. Beta2 microglobulin (B2M) and MHC II transactivator (CIITA) are critical for MHC I and II, respectively. MHCs are responsible for immunogenic recognition. Methods B2M and CIITA were knocked out from human iPSCs, either separately or simultaneously. The effects of single or dual knockout of B2M and CIITA on iPSC properties were evaluated in a xenogeneic model of human-to-monkey transplantation. Results B2M or CIITA knockout in human induced pluripotent stem cells (iPSCs) diminishes the expression of MHC I or II alleles, respectively, without changing iPSC pluripotency. Dual knockout was better than either single knockout in preserving the ability of human iPSCs to reduce infiltration of T and B lymphocytes, survive, and promote wound healing in monkey wound lesions. The knockouts did not affect the xenogeneic iPSC-induced infiltration of macrophages and natural killer cells. They, however, decreased the iPSC-promoted proliferation of allogeneic peripheral blood mononuclear cells and T lymphocytes in vitro, although not so for B lymphocytes isolated from healthy human donors. Although the dual knockout cells survived long enough for suiting therapeutic needs, the cells eventually died, possibly due to innate immune response against them, thereby eliminating long-term risks. Conclusions Having these iPSCs with diminished immunogenicity-recognizable to allogeneic recipient may provide unlimited reproducible, universal, standardized “ready-to-use” iPSCs and relevant derivatives for clinical applications. |
| Related Links | https://stemcellres.biomedcentral.com/counter/pdf/10.1186/s13287-020-01847-9.pdf |
| Ending Page | 14 |
| Page Count | 14 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17576512 |
| DOI | 10.1186/s13287-020-01847-9 |
| Journal | Stem Cell Research & Therapy |
| Issue Number | 1 |
| Volume Number | 11 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2020-08-03 |
| Access Restriction | Open |
| Subject Keyword | Stem Cells Cell Biology Regenerative Medicine Tissue Engineering Biomedical Engineering and Bioengineering Induced pluripotent stem cells Major histocompatibility complex Stem cell immunogenicity Non-human primate Wound healing Regenerative Medicine/Tissue Engineering |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Biochemistry, Genetics and Molecular Biology Molecular Medicine |
| Journal Impact Factor | 7.1/2023 |
| 5-Year Journal Impact Factor | 7.9/2023 |
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