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 αvβ3FAKERK Signaling Pathway

Abstract EN

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.