High Mannose N-Glycans Promote Migration of Bone-Marrow-Derived Mesenchymal Stromal Cells.

ABSTRACT: For hundreds of indications, mesenchymal stromal cells (MSCs) have not achieved the expected therapeutic efficacy due to an inability of the cells to reach target tissues. We show that inducing high mannose N-glycans either chemically, using the mannosidase I inhibitor Kifunensine, or genetically, using an shRNA to silence the expression of mannosidase I A1 (MAN1A1), strongly increases the motility of MSCs. We show that treatment of MSCs with Kifunensine increases cell migration toward bone fracture sites after percutaneous injection, and toward lungs after intravenous injection. Mechanistically, high mannose N-glycans reduce the contact area of cells with its substrate. Silencing MAN1A1 also makes cells softer, suggesting that an increase of high mannose N-glycoforms may change the physic

SUBMITTER: Alonso-Garcia V 

PROVIDER: S-EPMC7582662 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature