Improving engraftment potential of hMSCs after encapsulation in collagen microsphere: an in vitro and in vivostudy

Abstract

Stem cell-based therapies are promising in regenerative medicine. However, the

success of cell therapy is greatly limited by the low engraftment rate to the target

tissues.

The present study demonstrated that human mesenchymal stem cells (hMSCs)

were subjected to a self selection process via microencapsulation in collagen

barrier when they were induced to migrate out from this barrier. While retaining

the immuophenotype and self renewal capacity, the selected hMSCs showed a

significantly better in vitro migratory response of than those cultured in

traditional monolayer. The migratory response could be controlled by varying the

fabrication parameters of the collagen barrier, including initial collagen

concentration and cells seeding density. Affinity to adhere on endothelial cells

layer is another engraftment related property. Significant difference was observed

between these selected hMSCs and hMSCs in monolayer culture.

In order to investigate the engraftment potential of the selected hMSCs, an

animal model was performed. The selected hMSCs were transplanted

intravenously into NOD/SCID mice under partial hepatectomy. Presence of

human cells in the residual liver was determined by the presence of human

HLA-ABC using flow cytometry after 48 hours, 1 week and 1 month.

Engraftment of the selected hMSCs was significantly higher than that of

monolayer cultured hMSCs in time point of 1 month. It demonstrated that the

selected hMSCs favor the engraftment to the injured liver. Further investigation

is required to determine the fate of the engrafted hMSCs in order to truly confirm

their therapeutic potential.

The current work demonstrated that collagen-hMSCs microsphere could act as a

barrier to select hMSCs with enhanced in vitro migratory response and in vivo

engraftment properties. These findings may contribute towards the development

of better stem cell therapies.