hCTLA4-Gene-Modified Human Bone Marrow-Derived Mesenchymal Stem Cells (hBMMSCs) Maintain POSTN Secretion to Enhance the Migration Capability of Allogeneic hBMMSCs through the Integrin αvβ3/FAK/ERK Signaling Pathway
Cytotoxic T-lymphocyte-associated protein 4- (CTLA4-) modified human bone marrow-derived mesenchymal stem cells (hBMMSCs) might be promising seed cells for bone tissue engineering. However, the underlying mechanism is not clear. In the present study, we investigated whether CTLA4-modified hBMMSCs ar...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2020/3608284 |
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| Summary: | Cytotoxic T-lymphocyte-associated protein 4- (CTLA4-) modified human bone marrow-derived mesenchymal stem cells (hBMMSCs) might be promising seed cells for bone tissue engineering. However, the underlying mechanism is not clear. In the present study, we investigated whether CTLA4-modified hBMMSCs are involved in the migration of allogeneic hBMMSCs (allo-hBMMSCs) by maintaining POSTN secretion. hBMMSCs were isolated from different groups, named hBMMSCs and allo-hBMMSCs. hBMMSCs that were infected with the negative control (NC), empty adenovirus- or recombinant adenovirus-expressing CTLA4, POSTN, or CTLA4 plus the shRNA of POSTN were named NC hBMMSCs, CTLA4-modified hBMMSCs, POSTN-modified hBMMSCs, or CTLA4+shPOSTN-modified hBMMSCs, respectively. They were then cocultured with PBMCs in a 1 : 5 ratio with 2.5 μg/mL phytohemagglutinin (PHA). The coculture supernatant was collected to treat allo-hBMMSCs with anti-integrin αvβ3 IgG, or negative control IgG, as a control. Following this, ELISA, Transwell assays, wound healing assays, and western blotting were performed. We found that the POSTN level was higher in the culture supernatant of CTLA4- and POSTN-modified hBMMSCs than in NC hBMMSCs cocultured with PBMCs treated with PHA. The migration capability of allo-hBMMSCs was enhanced, and the integrin αvβ3/FAK/ERK signaling pathway in allo-hBMMSCs was activated by the culture supernatant of CTLA4- and POSTN-modified hBMMSCs cocultured with PBMCs treated with PHA. Additionally, these induced effects can be weakened by POSTN knockdown, and the migration capability of allo-hBMMSCs was blocked by anti-integrin αvβ3 IgG. In conclusion, hCTLA4-gene-modified hBMMSCs maintain POSTN secretion to enhance the migration capability of allogeneic hBMMSCs through the integrin αvβ3/FAK/ERK signaling pathway in the T cell immune activation environment. |
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| ISSN: | 1687-966X 1687-9678 |