Novel application method for mesenchymal stem cell therapy utilizing its attractant–responsive accumulation property

Abstract

AbstractObjectivesIt remains difficult to control the delivery of appropriate amounts of mesenchymal stem cell (MSC)-based cell therapies. To examine the ability of MSCs to accumulate at sites of damage and potential therapeutic benefit of providing continuous migration of MSCs to these sites, we observed the effect of MSCs administered in a collagen gel scaffold on healing of a tooth extraction site.Materials and MethodsMSCs isolated from the bone marrow of green fluorescent protein (GFP)-expressing donor mice were expanded for 3 weeks in three-dimensional (3-D) culture using a collagen gel scaffold, and evaluated to confirm the efficacy of the scaffold. Next, MSCs suspended in collagen gel were subcutaneously administered into the backs of mice. Two days later, extraction of the maxillary first molar was carried out. Numbers of MSCs in scaffolds, migration and accumulation around the extracted tooth cavity, extraction site healing, and presence of MSCs in vital organs were evaluated.ResultsMSCs cultured in the collagen gel scaffold maintained stemness for 2 weeks. After subcutaneous administration, numbers of MSCs in scaffolds slightly decreased over time, but cells survived for at least 2 weeks. After tooth extraction, GFP-expressing MSCs were confirmed in the surrounding mucosa of the extracted tooth cavity; in the scaffold group, numbers of MSCs increased over time and fewer were observed in lung tissue. Wound healing was enhanced by injection of MSCs via the tail vein or into the back compared with the untreated control group.ConclusionsDelivery in a collagen gel could maintain the characteristics of MSCs, which migrated to the damaged area and promoted wound healing without side effects occurring with conventional administration methods.