Hydrogel-based System for Mesenchymal Stem Cell Recruitment

Abstract

During the early stages of bone wound healing, mesenchymal stem cells (MSCs) in the bone marrow migrate to an injury site and differentiate into osteoblasts, which actively participate in the bone repair process. We proposed that a biomaterial system which enhances migration of endogenous MSCs may accelerate the tissue healing process. The aims of this study were to 1) identify and characterize an MSC chemoattractant, and 2) quantify the release kinetics of the chemoattractant from alginate hydrogels. Timelapse microscopy of 3D MSC migration was used for real time tracking of cell movement. Quantitative analysis of chemotaxis parameters identified Thymus Chemokine-1 (TCK-1) to be a potent MSC chemoattractant (p-values less than .01 for velocity, directionality, and forward migration index compared to controls). Qualitative receptor staining of MSCs in a transwell membrane assay showed that MSCs which respond chemotactically to gradient of TCK-1 express the TCK-1 cell receptor, CXCR2. An alginate hydrogel was used for controlled release of TCK-1. To characterize the kinetics of this system, an enzyme-linked immunosorbent assay (ELISA) was used to quantify TCK-1 release rates. This approach may be widely applicable to the regeneration of other tissue types and may be more efficient than the current multistep procedures of cell transplantation.